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Particles 2009 Micro and Nano Encapsulation 11-14 July 2009 Holiday Inn Berlin-City West, Berlin, Germany Graphic Courtesy of Jim Adair
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Page 1: Particles 2009

Particles 2009 Micro and Nano Encapsulation

11-14 July 2009 Holiday Inn Berlin-City West, Berlin, Germany

Graphic Courtesy of Jim Adair

Page 2: Particles 2009
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TABLE OF CONTENTS Sponsors 5

International Organizing Committee 7

Exhibitors 9

General Program Schedule 13

Map of Meeting Spaces 15

Technical Program 17

Abstracts 23

Speaker/Presenter Index 85

List of Preregistered Conferees 87

Notes 96

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Sponsors

5

Co-Sponsored by:

Particles Conference

and

European Association of Pharma Biotechnology

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Sponsors

6

Corporate Sponsor

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International Organizing Committee

J. M. Asua (Spain)

F. Boury (France)

D. Burgess (USA)

K. Caldwell (Sweden)

R. Duncan (UK)

M. El-Sayed (USA)

N. Garti (Israel)

K. Johnston (USA)

H. Kawaguchi (Japan)

J. H. Kim (Korea)

C. M. Lehr (Germany)

S. Margel (Israel)

H. Möhwald (Germany)

B. Moudgil (USA)

R. Mueller (Germany)

F. Nielloud (France)

T. Nilsen (USA)

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D. Poncelet (France)

M. C. Roco (USA)

P. Rogueda (UK)

J. L. Salager (Venezuela)

R. Sharma (USA)

S. Simoes (Portugal)

P. T. Spicer (USA)

S. Svenson (USA)

J. Texter (USA), General Chai

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Exhibitors

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Beckman Coulter, Inc. Beckman Coulter, Inc.

11800 S.W. 147th Avenue Miami, FL 33196-2500, USA Telephone: 1 800 526 3821

Fax: 1 800 232-3828 http://www.beckmancoulter.com

BüCHI Labortechnik AG Meierseggstrasse 40

Postfach CH-9230 Flawil 1

Switzerland Telephone: +41 71 394 63 63

Fax: +41 71 394 64 64 http://www.buchi.com

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Exhibitors

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Distrilab Particle Technology Olmenlaan 6C

3833 AV Leusden The Netherlands

Telephone: +31 33 494 78 34 Fax: +31 33 432 14 41 http://www.distrioab.nl/

NanoSight Limited Minton Park, London Road

Lysander Way Amesbury, Wiltshire SP4 7RT

United Kingdom Telephone: +44 (0)1980 676060

Fax: +44 (0)1980 624703 http://www.nanosight.co.uk/

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Exhibitors

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Surface Measurement Systems

5 Wharfside, Rosemont Road, Alperton, Middlesex HA0 4PE

United Kingdom Telephone: +44(0)208 795 9400

Fax: +44(0)208 795 9401 http://www.thesorptionsolution.com/

Surflay Nanotec GmbH 2 Centre One Lysander Way

Salisbury, Wilshire SP4 6BU United Kingdom

Telephone: +49 (0)30 6392 1764 Fax: +49 (0)30 6392 1767

http://www.surflay.com/

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General Program Schedule

Registration – Registration Desk (inside Atrium, outside Grand Saal entrance)

Saturday, July 11

(1800 – 2000) – Opening Reception, Mixer, & Exhibition (Atrium )

Sunday, July 12

(0830 – 1200) – General Session 1 (Grand Saal)

(1220 – 1400) – Luncheon & Exhibition (Atrium)

(1400 – 1730) – General Session 2 (Groser Saal)

(1800 – 2000) – Poster Session 1, Reception, & Exhibition (Atrium)

Monday, July 13

(0830 – 1200) – General Session 3 (Grand Saal)

(1200 – 1400) – Luncheon & Exhibition (Atrium)

(1400 – 1730) – General Session 4 (Grand Saal)

(1800 – 1930) – Poster Session 2, Reception & Exhibition (Atrium)

Tuesday, July 14

(0830 – 1200) – General Session 5 (Grand Saal)

(1200 – 1400) – Luncheon & Exhibition (Atrium)

(1400 – 1730) – General Session 6 (Grand Saal)

Conference Ends

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Map of Meeting Spaces

All Conference activities take place in the Großer Saal and in the Atrium on the ground floor just inside the main entrance and to the right of the main lounge and bar area. Registration commences Saturday morning, July 11th, at 9 am outside the Atrium. Registration opens at 8 am Sunday – Tuesday, 12-14 July.

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Technical Program

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Sunday Morning, July 12, 2009 General Session 1 (Großer Saal)

Session Chair: Diane Burgess, University of Connecticut 0800 General Announcements 0835 1. Keynote - Denis Poncelet, Enitiaa, CNRS 6144 GEPHA, Nantes Microencapsulation - Techniques and applications 0920 2. Rigoberto Advincula, University of Houston Electropolymerizable organic and hybrid dendrimers: Packaging of encapsulated

nanoparticles and electro-optical materials 0950 Break 1020 3. Gleb Sukhorukov, University of London Tayloring functions in microcapsules: Responsiveness and remote controlling 1050 4. Mathias Walther, Pfizer Polymers for controlled release 1120 5. Stefaan De Smedt, University of Ghent siRNA Dainecontaining nanoparticles: Stability of encapsulation and particle size 1150 6. Lars Daehne, Surflay Nanotec Layer by layer technology in industrial applications 1200 End of Session

Sunday Afternoon, July 12, 2009 General Session 2 (Großer Saal)

Session Chair: Gleb Sukhorukov, University of London 1400 7. Keynote - Gero Decher, University of Strasbourg New nano bags and micro pouches 1445 8. Diane Burgess, University of Connecticut Efficient and safe non-viral DNA delivery by anionic lipoplexes 1515 Break 1545 9. Andreas Fery, Univesity of Bayreuth Mechanical characterization of polymeric microcapsules using atomic force microscopy 1615 10. Thomas Scheibel, University of Bayreuth Spider silk for controlled drug delivery 1645 11. Alex M. van Herk, Eindhoven University of Technology Synthesis of multicompartment latex particles 1715 12. Ren Xu, Beckman Coulter Progress in nanomaterial characterization: Zeta potential determination 1730 - End of Session

Sunday Evening, July 12, 2009

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Technical Program

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Poster Session 1 (Atrium) Session Chair: Melanie Martin, Particles Conference 1730-1930 13. Ilke Akartuna, ETH Zurich Microcapsules from particle-stabilized emulsions 14. Erhan H. Altinoglu, The Pennsylvania State University Multifunctional near infrared emitting calcium phosphate nanoparticles for simultaneous

diagnostic imaging and photodynamic therapy 15. Gema Antequera-Garcia, Universidade de Vigo Low-fouling poly(N-vinyl pyrrolidone) capsules with engineered degradable properties 16. Cordin Arpagaus, Buchi Labortechnik AG Nano spray dryer - Submicron particles of minimal powder quantities at high yields 17. Ricardo B. Azevedo, Universidade de Brasilia Evaluation of itraconazole entrapped in nanospheres of PLGA for the treatment of

Paracoccidiodes Brasiliensis 18. Won San Choi, Korea Basic Science Institute Hierarchically nanostructured particles as a nanoreactor for synthesis of core-shell

particles 19. Andreas L. Christensen, University of Copenhagen Quantification of the encapsulation efficiency in single small unilamellar vesicles and

investigation of vesicle-DNA interactions 20. Sune M. Christensen, University of Copenhagen Single vesicle encapsulation and fusion: The design of an attofluidic biochip 21. Liesbeth J. De Cock, Ghent University Application of polyeledctrolyte capsules in the domain of tissue-engineering as carriers

for growth factor delivery 22. Loretta L. del Mercato, Philipps Universitat Marburg Uptake of colloidal polyelectrolyte multilayer capsules by living cells 23. Jiri Dohnal, ITC-Prague Use of drop-on-demand nozzle for microparticle production 24. Tristan Doussineau, Friedrich Schiller University Fluorescent ratiometric pH-nanosensors for biodiagnosis applications 25. Philipp Erni, Firmenich SA Interfacial rheology of surface-active biopolymers: Gum arabic vs. hydrophobically

modified starch 26. Chiara Giannachi, Bracco Imaging SpA Novel paramagnetic mixed micelles as potential MRI contrast agents 27. Kay Hettrich, Fraunhofer Institute for Applied Polymer Research, Golm Microencapsulation of biological objects with cellulose sulfate 28. Chutima Jantarat, Prince of Songkla University Molecularly imprinted nanoparticle-on-microsphere chiral cinchona-polymers for the

enantioselective-controlled delivery of racemic omprazole 29. Katsumi Kamegawa, NIAIST, Saga, Japan Production of hollow carbon microparticles from biomass resources 30. Vanja Kokol, University of Maribor Polyelectrolyte nano-assembled microcapsules for biosensing of glucose in human sweat 31. Pavel Kovacik, Institute of Chemical Technology Prague

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Technical Program

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Synthesis and controlled release characteristics of hollow SiO2 microparticles 32. Seta Küpcü, University of Natural Resources and Applied Life Sciences – BOKU Nanobiotechnological potential of S-layer coated liposomes 33. Jongwi Lee, Chung-Ang Universsity Electrohydrodynamic jetting of polymers using co-axial nozzles 34. Jongwi Lee, Chung-Ang Universsity Polymer-directed crystallization of atorvastatin 35. Dennis Lensen, University of Nijmegen Multi-functional poly urea formaldehyde capsules 36. Iratxe Madrietia-Pardo, INASMET-TECHNALLIA Double controlled release from hybrid materials containing microspheres and hydrogels

in vivo 37. Isabel M. Martins, University of Porto Microencapsulation by coacervation of biodegradable polymer with thyme oil 38. Olga Mykhaylyk, Technische Universität München Magnetic nanoparticles for gene delivery: Some determinants of efficient delivery vectors

Monday Morning, July 13, 2009 General Session 3 (Großer Saal)

Session Chair: Cornelia Keck, PharmaSol GmbH 0835 39. Keynote - Ronald Versic, R.T. Dodge

Industrial encapsulation processing 0920 40. Ian Marison, Dublin City University

Liquid-core micro and nanocapsules for the extraction of drugs and pesticides/herbicides 0950 Break 1020 41. Bruno De Gheest, University of Ghent

Degradable polyelectrolyte capsules for biomedical applications 1050 42. Christian Quellet, Givaudan

Fragrance encapsulation in micro and nanoparticles 1120 43. Thorsten Brandau, BRACE GmbH

Manufacturing microcapsules for advanced materials 1150 End of Session

Monday Afternoon, July 13, 2009 General Session 4 (Großer Saal)

Session Chair: Thorsten Brandau, BRACE GmbH 1400 44. Keynote - Helmuth Möhwald, Max Planck Institute of Colloids and Interfaces Microcapsules with controlled and remote release 1445 45. Cornelia Keck, PharmaSol GmbH Lipid nanoparticles for the delivery of actives in pharma, cosmetics and consumer care

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Technical Program

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1515 Break 1545 46. Gulden Yilmaz, Wageningen University and Research Centre One processing technology - Variable applications 1615 47. Jean Antoine Meiners, MCC s.a. Particle engineering to design protection and release of microencapsulated bioactives 1645 48. Berit L. Strand, Norwegian University of Science and Technology Encapsulation with alginates 1715 - End of Session

Monday Evening, July 13, 2009 Poster Session 2 (Atrium) Session Chair: Melanie Martin, Particles Conference 1730-1930 49. Lise Junker Nielsen, University of Southern Denmark Peptide mediated delivery of opticdal nanosensors into S. cerevisaes 50. Tsutomu Ono, Okayama University Development of nanoparticles containing photosensitizer with diblock copolymer for

photodynamic therapy 51. Veli Cengiz Ozalp, University of Southern Denmark Aptamer embedded polyacrylamide nanoparticles used as nanosensors for metabolite

detection in vivo 52. Isabel Pastoriza-Santos, Unidad Asociada CSIC-Universidade de Vigo Encapsulation of gold nanparticles in a PNIPAM microgel: Nanoreactors and molecular

traps for SERS 53. Rafael Piñol, Universidad de Zaragoza Smectic polymer vesicles 54. Rafael Piñol, Universidad de Zaragoza Multi-stimuli responsive poly(4-vinyl pyridine) nano- and microspheres as candidates for

remote controlled drug delivery 55. Clive A. Prestidge, University of South Australia Hybrid nanostructured microcapsules composed of silica nanoparticles and lipid

emulsions: Encapsulation and delivery of poorly soluble drugs 56. Pilar Rivera Gill, Philipps University of Marburg Delivery of microcontainer with active components to cells 57. Sofia N. Rodrigues, University of Porto Synthesis of polyurethane-urea microcapsules with perfume for textile application 58. Virginia Sáez-Martínez, INASMET-TECNALIA Controlled release studies of dexamethasone from nanometric hydrogels for ophthalmic

applications 59. Yuika Saito, Osaka University Photopolymerization of fullerenes encapsulated in SWCNT 60. M. Magdalena Sánchez-Navarro, INESCOP Melamine-formaldehyde microcapsules containing eucaliptus essential oil for footwear

applications 61. Gitte Sørensen, Danish Technological Institute Slow release of biocide from silica microparticles in wood paints

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Technical Program

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62. Antonio Stocco, Université Paris-Sud Silica nanoparticles at air-water interfaces 63. Antonio C. Tedesco, Universidade de Sao Paulo In vitro cellular phototoxicity of nanocapsules containing a metallophthalocyanine on

B16-F10 Melanoma cells 64. João Tedim, University of Aveiro Layered double hydroxide nanocrystals loaded with exchangeable anions for controlled

corrosion protection 65. John Texter, Eastern Michigan University and Max Planck Institute, Golm New di-stimuli responsive di-hydrophilic diblocks for chemical delivery 66. Benjamin Thierry, University of South Australia Hybrid plasmonic colloidal nanostructures 67. Doris Vollmer, Max Planck Institute for Polymer Research, Mainz Mechanical properties of single hollow silica particles 68. Dennis M. Vriezema, Encapson BV Encapsulation as a business 69. Yanhong Wen, University of Copenhagen Development of activated spherical particles as a scaffold for tissue regeneration 70. Ren Xu, Beckman Coulter, Inc. Development of amorphous drug nanoparticles by NovaSperse™ technology 71. Ales Zadrazil, Institute of Chemical Technology Prague Synthesis and controlled release from polymer microsponges

Tuesday Morning, July 14, 2009 General Session 5 (Großer Saal)

Session Chair: Pei Li, Hong Kong Universityof Science and Technology 0830 General announcements; presentation of PlasmaChem Prize 0835 72. Harm-Anton Klok, EPFL Facile and convergent synthesis of polymer-coated gold nanoparticle libraries 0905 73. Angus Johnston, University of Melbourne Assembly of bioinspired, nanoengineered materials for targeted drug delivery 0935 74. Anna Musyanovych, Max Planck Institute for Polymer Research, Mainz Formation of smart nanocapsules for defined slow or sudden release 1005 Break 1030 75. Edwin Donath, University of Leipzig Engineering particles with biointerfaces employing viral architectures 1100 76. Dmitry Shchukin, Max Planck Institute of Colloids and Interfaces Nanocontainers with controlled permeability for feedback active coatings 1130 77. Heidi Johnsen, SINTEF Emulsion based encapsulation 1200 End of Session

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Technical Program

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Tuesday Afternoon, July 14, 2009 General Session 6 (Großer Saal)

Session Chair: John Texter, Eastern Michigan University and Max Plamck Institute for Colloids and Interfaces

1400 78. Pei Li, Hong Kong University of Science and Technology Amphiphilic core-shell particles in advanced waste water treatment technology technology 1430 79. Simona Margutti, Fraunhofer IAO, Stuttgart Encapsulation approaches in advanced display technology 1500 Break 1530 80. Matthieu Bedard, Queen Mary College Optically addressable microcapsules 1600 81. Keynote - Jim Adair, Penn State University Inorganic encapsulation of organics for imaging and delivery 1645 Panel Discussion - Diane Burgess, Rainer Mueller, Denis Poncelet, and Ronald

Versic Discussion of Conference Issues 1715 End of Conference

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Abstracts

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General Session 1 – Keynote Paper

1 MICROENCAPSULATION : METHODES AND AND TECHNOLOGIES, Denis Poncelet, ENITIAA, UMR CNRS 6144 GEPEA, Rue de la Géraudière, BP 82225, 44322 Nantes Cedex 3, France; [email protected]

Biological cells are an incredible system allowing life to develop by immobilizing, protecting, controlling the transfer, structuring and functionalising the actives. Researchers and engineers tends to mimic them by producing microcapsules with already a large range of applications and event more potential ones, in all domains of our daily life. Face to the diversity of applications and the multidisciplinary aspects of the microencapsulation, it is quite difficult to understand how to select the most adequate method in function of a specific request and to find optimum conditions to develop a process. The talk will then cover both the understanding of why making encapsulation, which questions must be introduced to select a method and how to classify the different technologies. General Session 1 – Invited Paper

2 ELECTROPOLYMERIZABLE ORGANIC AND HYBRID DENDRIMERS: PACKAGING OF ENCAPSULATED NANOPARTICLES AND ELECTRO-OPTICAL MATERIALS Rigoberto Advincula, Department of Chemistry and Department of Chemical Engineering, University of Houston, Houston, Texas, USA 77204; [email protected]

Organic polymer and hybrid materials are of high interest for investigating structure-property relationships that extends from composite materials to core-shell nanoparticle systems. In particular, the utilization of dendrimeric systems and their ability to have various levels of functionality with the core, generation, or peripheral group makes them ideal for hybrid material system investigations. The synthesis of organic dendrimers involves either a convergent or divergent approach. The key strategy involves a selective exponential growth of the functionality both at the branching point and at the periphery. In this work we demonstrate the two possibilities of synthetic routes for packaging and isolating nanoparticles through the electropolymerizability of the corresponding peripheral groups. This involves the synthesis of dendrons that can act as capping agents or shell layers to package or host nanoparticles (metal or semiconductor) and their corresponding electro-optical properties. On the other hand the use of existing dendrimers such as PAMAM enable the hosting of catalytic nanoparticles capable of selective adsorption properties on electrodes. The ability to simultaneously target encapsulation simultaneous with the intrinsic hybrid electro-optical property is important. Lastly, the electropolymerizability of the peripheral groups make them ideal for specific applictions as nano-objects, photovoltaic, and sensor devices.

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General Session 1 - Invited Paper

3 TAILORING FUNCTIONS IN MICROCAPSULES: RESPONSIVENESS AND REMOTE CONTROLLING Gleb Sukhorukov, School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, E1 4NS, London, United Kingdom; [email protected]

Layer-by-layer assembled capsules are owing to their ability to encapsulate a wide range of chemicals, for their permeability to be modified and their responsiveness to different factors and functionalities to be tailored in one capsule entity. Composite polymer/nanoparticles capsules with tailored functions represent a novel type of microcontainers with multifunctional properties. These capsules are made by layer-by-layer adsorption of oppositely charged polyelectrolytes on colloidal template particles, including emulsions, drug nanoparticles and gas bubbles, of 0.05 – 20 µm diameter with sequential removal of the template core. A great variety of materials including synthetic and natural polyelectrolytes, proteins, multivalent ions, organic nanoparticles, lipids were used to build walls of hollow capsules. The possibility of tailoring different functionalities, impregnating inorganic and organic substances both inside capsule volume and in polyelectrolyte shell, controlled release of encapsulated material provided continuous scientific and industrial interest for employing capsules as microcontainers and microreactors. Smart polymers involved in capsule build-up exhibit reversible sensitivity to environmental conditions, such as temperature, pH, ions, etc. Inorganic nanoparticles incorporated to polyelectrolyte shell makes possible the remote activated release by ultrasound or infrared radiation as well as to guided by magnetic field. Multifunctional (several properties in one entity) capsules make them unique for many: controlled drug delivery, absorbents for solvent extractions, separation processes, sensors or actuators. The possibilities for practical applications on living systems are illustrated on cell culture level. Current research leads to the fabrication of carriers with remote guiding and activation by optical, magnetic and ultrasound addressing, what envisages unique applications as multifunctional biomaterials in-vivo. Submicron sized capsules are good model to mimicking bio-chemical processes in a confined geometry imitating cell organelles, whilst delivered inside cell and tissues the capsules could serve as intracellular reporter or enzymatic reactor. General Session 1 – Invited Paper

4 POLYMERS FOR CONTROLLED DRUG RELEASE APPLICATIONS - USING FILM MICROSTRUCTURE TO CONTROL PERFORMANCE Mathias Walther, Pfizer Ltd, Sandwich, Kent, CT13 9NJ, United Kingdom; [email protected]

Polymers are routinely used as coating materials to control drug release from multiparticulate pharmaceutical dosage forms such as microspheres, pellets, granules etc. The need to deliver drugs with a wide range of physico-chemical properties and specific pharmaco-kinetic treatment targets has resulted in the development of various approaches that utilize available pharmaceutical grade polymers and create novel functionality by combining materials with different properties. This presentation provides an overview with practical examples to illustrate different strategies that are routinely used to adjust

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coating functionality. In particular, the use of polymer blends is discussed as it offers major advantages, including: (i) facilitated adjustment of desired drug release patterns, mechanical properties and drug release mechanisms, (ii) improved film formation and storage stability, and (iii) the possibility to develop novel strategies for site specific drug delivery within the gastro intestinal tract (e.g., colon targeting). The microstructure of the film coat is critical to control performance and can be affected by formulation variables and materials properties as well as the manufacturing process. Consequently, the increased complexity of such systems makes optimization and scale-up more challenging. A fundamental understanding of the underlying drug release mechanisms coupled with an insight into the film microstructure is highly desirable to render the optimization of this type of advanced delivery systems more efficient. General Session 1 – Invited Paper

5 siRNA CONTAINING NANOPARTICLES: STABILITY OF ENCAPSULATION AND PARTICLE SIZE Kevin Buyens, Kevin Braeckmans, Niek N. Sanders, Joseph Demeester and Stefaan C. De Smedt, Ghent Research Centre on Nanopharmacy, Department of Pharmaceutics, University of Ghent, Harelbekestraat 72, 9000 Ghent, Belgium; [email protected]

A lot of efforts are currently made in the development of nano-scaled carrier systems that can guide siRNA molecules to their target cells after intravenous injection. One of the main issues in this research is the integrity of the siRNA containing nanoparticles in the blood stream. The integrity of the nanoparticles comprises both the particle size and the stable encapsulation of the siRNA. Techniques currently available for studying the disassembly and size distribution of siRNA containing nanoparticles are time-consuming and incompatible with biological fluids. First we developed a fluorescence fluctuation spectroscopy (FFS) based method which allows to monitor the integrity of siRNA-carrier complexes in less than one minute in complex biological media and at very low siRNA concentrations. Second, while the size distribution of the complexes can be easily measured in a clear dispersion by dynamic light scattering or electron microscopy, it cannot be measured in more complex biological media such as plasma or whole blood, which contain all kinds of interfering components. To address this issue, we have developed a novel technique, based on single particle tracking (SPT) microscopy, for studying the size distribution (and aggregation) of nanoscopic drug complexes in biological fluids. For stabilization of the particle size of cationic lipid based nanoparticles, inclusion of lipids conjugated with PEG are widely used to sterically hinder aggregate formation. We have demonstrated that in order to obtain remaining siRNA complexation to the cationic liposomes, effective encapsulation inside the liposome, or in between lipid multilayers is required, since siRNA electrostatically bound to the outer side of the liposomes is quickly pushed away by the ubiquitous albumin molecules in blood which leads to siRNA degradation and loss of effectiveness. Formation of siRNA protecting multilayers is hindered by inclusion of PEG-lipids, a hurdle that needs to be overcome by either post-insertion of the PEG-lipid into multilayer containing siRNA-liposome complexes, or by efficient encapsulation of the siRNA inside the aqueous core of the PEGylated liposome.Size stabilization in buffer can be easily achieved by inclusion of minor percentages (~1%) of PEG-lipids. In whole blood however, we demonstrate that much higher percentages of PEG-lipids (5-10%) are

Figure 12

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required to achieve size stabilization. The latter being a fact that has not been taken into account sufficiently up until now, because of the lack of a suitable technique to study the aggregation phenomena in whole blood.In our work we demonstrate that assaying the physicochemical properties of siRNA encapsulating nanoparticles should always be carried out in the biological media they are designed to be employed in. Two novel microscopy based methods were developed that enable such characterization in biological fluids like serum, plasma or even whole blood. General Session 1 – Exhibitor Focus Paper

6 LAYER BY LAYER TECHNOLOGY IN INDUSTRIAL APPLICATIONS Lars Dähne, Gabriella Egri, Jing Kang, Barbara Baude, Surflay Nanotec GmbH, [email protected]

Since the development of the LbL technology by Gero Decher et.al. a currently increasing scientific community was developing a huge amount of possible solutions and applications by means of LbL both on planar surfaces and colloidal templates. However, despite of this high future potential only very few technical applications are known up to now. Our company is trying to bring some of the most promising developments to the market but the traditional industry is rather defensive about this technology because of questions about biocompatibility, stability, price, permeability etc. We will present three actual developments of LbL-coated particles of our company and highlight the possible advantages and also drawbacks of these particles against traditional beads. These developments are in the field of

- none-sedimenting 3 µm air-filled beads (bubbles) - DNA-sensitive beads with high hybridization efficacy

LbL modified bioseparation materials General Session 2 – Keynote Paper

7 NEW NANO BAGS AND MICRO POUCHES Gregory F. Schneider, Vladimir Subr, Karel Ulbrich, and Gero Decher; Centre National de la Recherche Scientifique (CNRS UPR 22), Institut Charles Sadron, 23 rue du Loess, F-67034 Strasbourg, France; Université de Strasbourg, 1 rue Blaise Pascal, F-67008 Strasbourg-Cedex, France; and Institute of Macromolecular Chemistry, Heyrovsky Sq. 2, 162 06 Prague 6, Czech Republic; contact: [email protected]

Materials Science has always been driven by the desire to transform matter into some-thing more useful, which is typically also thought to be more valuable. One of the impor-tant tools for creating order is molecular self-organization based on molecules which undergo molecular self-assembly. However, even simple devices are often multimaterial composites with a complex and sometimes even hierarchical structure. It is evident that basic self-assembly methods will not be able to address molecular organization at this level and, as a consequence, multistep assembly procedures will need to be employed for the (nano)fabrication of such materials or devices. Layer-by-layer (LbL) assembly has, in the last years, developed into a method, which begins to make it possible to construct multimaterial soft-matter devices by rational design. The examples of hybrid

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nanomaterials discussed at this conference are new cytotoxic stealth nanoparticles made by LbL-deposition (I) and “nanobags” which are made by a process based on flocculation (II). I.) We report on a highly versatile nanoparticle-based core/shell drug delivery system consisting of cytotoxic stealth carrier particles. Their multifunctional shells, mandatory for addressing different diagnostic/treatment requirements, are constructed by robust electrostatic and covalent layer-by-layer assembly leading to nanoparticles with multilayer shells that combine all of the following properties: (i) a small size distribution of the nanoparticle carrier, (ii) a high stability in physiological media, (iii) attachment of a pro-drug in covalent form and thus a low toxicity of the carrier system, (iv) the trig-gered release and activation of the drug only after endocytosis and enzymatic cleavage, and (v) “stealthiness” and thus protection against uptake by macrophages. II.) The control of simple parameters involved in the process of classic bridging floccu-lation allows the preparation and fine-tuning of a new class of hybrid nanomaterials with respect to size, composition, and morphology. The resulting nanoparticle-filled “nano-bags” are obtained in aqueous suspension by mixing three basic components, a polyelec-trolyte, a multivalent ion, and nanoparticles in different ratios. The size range in which nano- and micropouches can be prepared seems to start at about 25 nm; these are oligo-nanoparticle aggregates whose size are clearly related to the size of the nanoparticles themselves and seem to extend up to about 5 µm. By controlling the stoichiometric balance between the global number of positive and negative charges on the polycation and on the multivalent anion and by controlling the absolute concentrations and the ratios, namely of the polyelectrolyte and the nanoparticles, one has access to a wide range of different nanopouch morphologies and compositions. General Session 2 – Invited Paper

8 EFFICIENT AND SAFE NON-VIRAL DNA DELIVERY BY ANIONIC LIPOPLEXES Charudharshini Srinivasan, Mamta Kapoor and Diane J. Burgess; Department of Pharmaceutical Sciences, 69 North Eagleville Road, Unit 3092, University of Connecticut, Storrs, CT 06269, USA. [email protected]

The success of gene delivery depends on efficient cellular delivery of DNA-based therapeutics using physiologically safe vectors. Recently a lot of attention has been given to cationic lipids and polymers as well as polymeric nanoparticles non-viral vectors. In an effort to improve the safety of non-viral vectors the use of an anionic lipid carrier system, comprising divalent cation mediated, DNA and anionic liposome complexes (lipoplex), is explored in this study. Anionic liposomes comprised of mixtures of anionic/zwitterionic lipids ((DOPG/DOPE) at varying molar ratios (10/90 to 50/50)) were prepared by rotary evaporation method. The anionic lipoplexes were formed by complexing the liposomes with plasmid DNA (pEGFP) and a divalent cation, Ca 2+. Lipofectamine 2000 was used as a control. Transfection was conducted in CHO-K1 cells in presence of serum and quantitative EGFP expression analysis was conducted by spectrofluorimetric analysis in a FLUOstar Optima microplate reader. MTT (3-[4,5-

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dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) colorimetric assay was performed to determine toxicity. Particle size analysis, zeta potential, gel electrophoresis, transmission electron microscopy and confocal studies were performed for liposomes and lipoplex characterization studies. DNA molecules formed stable complexes with anionic liposomes and optimum transfection efficiency occurred at 15 – 20 mM Ca 2+ and a 20/80 (anionic/zwitterionic) lipid molar ratio with lipid/DNA ratios at 15 – 20 µg/0.8 µg. The transfection efficiency of anionic lipoplex (~78% ) was comparable to the cationic Lipofectamine2000/DNA complex (~68%). Lipofectamine 2000/DNA complex resulted in high toxicity compared to anionic lipoplexes. Cell viability of anionic lipoplex (~93%) was much higher than the Lipofectamine2000/DNA (~35%). Particle size analysis, gel electrophoresis, transmission electron microscopy and confocal studies assisted in characterization of optimized anionic lipoplex formulations. The anionic lipoplexes labeled with rhodamine-PE to track the lipoplexes intracellularly and nucleus stained with SYTO-45 blue nuclear stain revealed that the lipoplexes were localized at the peri-nuclear region following 3 h incubation in CHO-K1 cells. The anionic lipoplexes appear to be a suitable candidate for DNA delivery with comparable transfection efficiencies to cationic lipids and significantly less cytotoxicity. General Session 2 – Invited Paper

9 MECHANICAL CHARACTERIZATION OF POLYMERIC MICROCAPSULES USING ATOMIC FORCE SPECTROSCOPY Andreas Fery, Department of Physical Chemistry II, University of Bayreuth, Universiteatsstr. 30, D95444 Bayreuth, Germany; [email protected]

Mechanical properties of microcapsules govern (mechanical) stability, deformation behavior and influence adhesion. Thus techniques that allow for characterization of individual microcapsules are of interest for fundamental science just as well as for various fields of application. The talk summarizes results obtained from AFM-based single-capsule deformation experiments with a focus on stimulus responsive systems like polyelectrolyte multilayer shells. Deformation properties can be investigated in aqueous environment and parameters like pH, salt concentration or temperature can be varied in situ. Continuum mechanical modeling can explain the observed deformation forces and provide guidelines for achieving responsive capsule systems with tailored mechanical properties. Especially for more complex systems like Pickering emulsion droplets or gas filled particles (microballoons), complementary information on shape changes in various stages of deformation is essential. This can be achieved by combination of AFM with optical techniques like micro-interferometry or fluorescence microscopy. We discuss findings on these systems and give an outlook on future perspectives. General Session 2 – Invited Paper

10 SPIDER SILK FOR CONTROLLED DRUG DELIVERY Andreas Lammel1, Martin Schwab3,Gerhard Winter3, Thomas Scheibel2; 1Lehrstuhl Biotechnologie, Lichtenbergstraße 4, Technische Universität München, D-85747 Garching, Germany; 2Lehrstuhl Biomaterialien, Universitätsstraße 30, Universität Bayreuth, D-95440 Bayreuth, Germany;

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3Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität, D-81377 Munich, Germany; [email protected]

Biological materials often exceed the characteristics and properties of man-made ones. One well-known example is spider silk with superior mechanical properties such as strength and toughness. Most spider silks are used for building the web, which reflects an optimized trap for flying prey. Already thousands of years ago the excellent mechanical properties and low immunogenicity of spider webs have been acknowledged by men, employing them as fishing nets or as wound closure devices. However, large-scale farming of spiders has been quickly abandoned due to the territorial and cannibalistic behavior of most spiders. In order to avoid such complication, we developed a bio-inspired system using bacteria as production hosts which produce silk proteins mimicking the natural spider silks. Our engineered spider silk proteins can be processed into fibers, but also into particles which can be used as drug carriers. Silk particles are colloidaly stable in solution and can be efficiently loaded. In vitro release studies showed that constant release rates at physiological conditions can be realized for a period of two weeks. Silk particles have a huge potential for diverse applications with desired controlled release from biocompatible carriers. General Session 2 – Invited Paper

11 SYNTHESIS OF MULTICOMPARTMENT LATEX PARTICLES Alex M. van Herk*, Syed Imran Ali, Hans Heuts, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands; [email protected]

In the field of encapsulation of many types of particles like pigments, fillers and clay particles [1,2] tremendous progress has been made and applications of encapsulated inorganic particles are known, for example in car coatings. Core-shell latex particles are applied for many decades. Encapsulation of all kind of materials like pigment particles, filler particles and magnetic particles is known. A new challenge is in the encapsulation of clay platelets striving towards a high aspect ratio of the resulting nanostructured particles. One is struggling with surface tensions there and the thermodynamic driving force to small surface area. Similar problems exist in the field of vesicle polymerization [3]. After careful studies it turned out to be very difficult to produce a thin wall of polymer inside the hydrophobic domain of the vesicle double layer. The most common structure produced is that of the parachute, a latex particle connected to the vesicle structure. Apparently only with strong covalent bonds between the surfactant and the polymer one is able to produce hollow particles through vesicle polymerization. The field of vesicle polymerization opens many possibilities to produce many different and interesting new nanostructured particles. Specialty applications like intraocular eye lenses bases on transparent latices are showing the enormous potential of nanocomposites in the area of specialties [4]. In this paper it will be shown that many different multicompartment structures can be produced while applying the general principles of thermodynamics and kinetics in emulsion polymerizations. One example are the so-called nanobottles where a hollow structure is combined with a latex particle making a lid for the ‘nanobottle’ (see Figure 1). The authors wants to ackowledge Dirk-Jan Voorn, Martin

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Jung, Jens Pusch, Jens Hartig and Marshall Ming for their important contributions on the development of this research line 1. D.J. Voorn, W. Ming, A.M. van Herk, Clay Platelets Encapsulated Inside latex Particles, Macromolecules 2006, 39, 4654-4656 2. A.M. van Herk and A.L. German, "Microencapsulated pigments and fillers", contribution to the book 'Microspheres, Microcapsules & Liposomes', vol 1 : Preparation & Chemical Applications, Citus Books, London , ed Prof. R Arshady (1999) 3. M. Jung, D.H.W. Hubert, P. Bomans, P.M. Frederik, A.M. van Herk, A.L. German "A Topology map for novel vesicle-polymer architectures" Advanced Materials 12 2000 210-213 4. J. Pusch, A.M. van Herk Emulsion polymerization of novel transparent latices with pulsed electron beam initiation Macromolecules 38 2005, 6939-6945

Figure 1. One of a kind nanobottle produced in vesicle polymerization (normal particles look more spherical). General Session 2 – Exhibitor Focus Paper

12 ROGRESS IN NANOMATERIAL CHARACTERIZATION: ZETA POTENTIAL DETERMINATION Ren Xu, Beckman Coulter Inc., Miami, FL, USA; [email protected]

Zeta potential measurement of particles in suspension is a very important research tool and quality control means for dispersion stability and product performance of nano or submicron particulate materials and has been transformed from an explorative tool to a must-have means in recent years. There are two technologies that are commonly used for zeta potential measurement, i.e., electrophoretic light scattering (ELS) and acoustic. The ELS technology produces accurate and high resolution results for particles in either aqueous or non-aqueous suspensions. However, its current applications are limited to dilute samples due to the conventional optical arrangement. It is important to measure zeta potential of particles in their native environment, which is often a concentrated suspension, since zeta potential of particles is a property of the particles as well their environment. Improper dilution often produces correct but irrelevant information. In this presentation, a patented technology (FST) used for ELS measurement will be introduced. In the FST technology, measurements are performed on particles near a transparent

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electrode therefore avoiding multiple scattering and scattering attenuation due to high solid concentration. The knowledge of surface charge (zeta potential) of solid surfaces, such as engineered membranes, fabrics, and celluloses, is important to understand, predict or modify surface properties of these materials. However, there have been few effective ways to measure surface charge of flat surface immersed in liquid. A new electroosmotic probing method to determine surface charge of flat surface in liquid will be described. Poster Session 1 – Contributed Paper

13 MICROCAPSULES FROM PARTICLE-STABILIZED EMULSIONS I. Akartuna, P. N. Sturzenegger, U. T. Gonzenbach, E. Tervoort, A. R. Studart, L. J. Gauckler; Department of Materials, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland; [email protected]

Microencapsulation holds the potential to overcome a number of challenges in technology ranging from targeted administration of chemicals over controlled release to screening active agents from environmental influence. Although a considerable variety of surfactant and polymer based encapsulation methods are already developed to solve specific problems, a platform technology for microencapsulation does still not exist. Particle-stabilized systems are potential candidates to provide new solutions in the field of micro-encapsulation due to the great freedom in the selection of materials and their outstanding properties. Here we present a processing route for the fabrication of microcapsules from particles via emulsion templating. The assembly of particles at the oil-water interface is induced by the in situ hydrophobization of the particle surface through the adsorption of short amphiphilic molecules. The adsorption of particles at the interface leads to highly stable emulsions with tailorable microstructures. Dilution of these emulsions results in wet capsules that can be harvested into hollow capsules upon drying. Organic binders are used to increase the mechanical integrity of the capsule shell. This process allows the fabrication of capsules with controlled sizes and compositions using wide variety of colloidal particles. These solid-coated microcapsules are expected to offer several advantages compared to amphiphilic and polymeric vesicles such as mechanical and chemical robustness, temperature resistance and better environmental compatibility. Poster Session 1 – Contributed Paper

14 MULTIFUNCTIONAL NEAR INFRARED EMITTING CALCIUM PHOSPHATE NANOPARTICLES FOR SIMULTANEOUS DIAGNOSTIC IMAGING AND PHOTODYNAMIC THERAPY E. İ. Altınoğlu*, T. Russin#, B.M. Barth+, S. Saravanan+, P. C. Eklund*#, and J. H. Adair*, *Department of Materials Science and Engineering, #Department of Physics, +Hershey Medical Center, Department of Pharmacology, The Pennsylvania State University, University Park, PA 16802, USA; [email protected]

Simultaneous early detection and treatment are crucial elements for the timely diagnosis and successful eradication of all cancers, but are limited by the sensitivity and efficacy of

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current imaging and therapeutic methodologies, respectively. Thus, much interest has initiated in both near infrared (NIR) contrast agents for sensitive, deep tissue imaging, and non-toxic photosensitizers for noninvasive, localized, molecular-scale photodynamic therapy. The full potential of such concurrent early stage diagnosis and treatment lies in the ability to engineer multifunctional vectors with unique optical properties that can penetrate early-stage lesions with a high-level of targeted specificity and maximum photostability while simultaneously prompt a localized photodynamic response to initiate cell death. Here we report the synthesis of bioresorbable calcium phosphate nanoparticles (CPNPs) which encapsulate molecules of the NIR fluorophore indocyanine green (ICG) for use as a fluorescent photosensitizer agent for synchronized real-time, deep-tissue imaging and therapy. These ICG-CPNPs demonstrate exceptional colloidal and optical characteristics. Suspensions consisting of 16 nm average diameter particles are colloidally stable in physiological solutions (phosphate buffered 0.15 M saline (PBS), pH 7.4) with polyethylene glycol (PEG) surface passivation. The doped CPNPs exhibit significantly greater intensity at the maximum emission wavelength relative to the free constituent fluorophore, consistent with the multiple molecules encapsulated per particle. The quantum efficiency per molecule of the ICG-CPNPs is 200% greater at 0.049±0.003 over the free fluorophore in PBS. Photostability based on fluorescence half-life of encapsulated ICG in PBS is 500% longer under typical clinical imaging conditions relative to the free dye. Furthermore, the ex situ generation of singlet oxygen (1O2) from these multifunctional vectors is matched by exceptional in vivo photodynamic responses. PEGylated ICG-CPNPs accumulate in solid, 5 mm diameter xenograft breast adenocarcinoma tumors via enhanced retention and permeability (EPR) within 12 h after systemic tail vein injection in a nude mouse model. Moreover, after a single localized dosage of 785 nm light (50 J/cm2), tumor growth is completely arrested over 36 days, whereas untreated controls grow to over 10 times their initial size. Experimental ex situ data are also used to theoretically model clinical deep-tissue imaging and therapeutic performances with NIR signals detectable at depths up to 10 cm and therapeutic photodynamic responses initiated from 7 cm in breast tissue. With these superior optical properties, inherent singlet oxygen generation, and promising in vivo photodynamic performances, ICG-CPNPs can impart an improved parallel approach to sensitive early-stage diagnosis and site specific therapy. Poster Session 1 – Contributed Paper

15 LOW-FOULING POLY(N-VINYL PYRROLIDONE) CAPSULES WITH ENGINEERED DEGRADABLE PROPERTIES Gema Antequera-García,# Cameron R. Kinnane,† Georgina K. Such,† Yan Yan,† Sarah J. Dodds,† Luis M. Liz-Marzan,# and Frank Caruso†*

#Colloid Chemistry Group, Departamento de Química Física and Unidad Asociada CSIC, Universidade de Vigo, Vigo 36310, Spain; †Centre for Nanoscience and Nanotechnology, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia; Email: *[email protected]; #[email protected]

Hollow polymer capsules have generated significant scientific and technological interest over the past decade because of their promise for application as microreactors, specific targeting and sensors. To date, the most versatile method used for assembling such

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capsules is the layer-by-layer (LbL) assembly of complementary interacting polymers onto a colloidal template. We present here the preparation of low-fouling capsules with tailored deconstruction properties for drug delivery. The capsules were assembled via the LbL assembly of poly(N-vinyl pyrrolidone)Alkyne (PVPONAlk) and poly(methacrilic acid) (PMA) by hydrogen bonding onto sacrificial silica templates. Alkyne moieties were used to cross-link the multilayer with a degradable bisazide functional molecule through click chemistry, resulting in capsules composed primarily of PVPON. The PVPON multilayers are low-fouling in the presence of a number of fluorescently-labeled proteins and the resulting capsules showed no effect on the proliferation of cells by MTT assay. Cells incubated with various concentrations of capsules showed minimal change in proliferation as compared with untreated samples, thereby highlighting the biocompatiblility of the capsules. Additionally, capsules stabilized with a linker containing a disulfide group (which is capable of being cleaved under reducing conditions) are shown to deconstruct in the presence of 5 mM glutathione. The low-fouling properties of these capsules render them attractive materials for bioreactors, biomarkers or drug delivery. Poster Session 1 – Contributed Paper

16 NANO SPRAY DRYER –SUBMICRON PARTICLES OF MINIMAL POWDER QUANTITIES AT HIGH YIELDS Cordin Arpagaus, Business Area Spray Drying, Büchi Labortechnik AG, Meierseggstrasse 40, 9230 Flawil, Switzerland, [email protected]

Spray drying is recognized as one of the few industrial drying processes that produce powders directly from liquid feed formulations in an operation that is continuous, easy to control, economical, environmentally friendly and safe. It is widely used in the pharmaceutical, biotech, food & feed, chemical and material industries. Today, there is a high research activity in the preparation of spray dried nanoparticulate materials for novel drug delivery systems (e.g. inhalable drugs in the form of nanocapsules, -suspensions or -emulsions). A new spray dryer is described that features a unique vibrating mesh spray generation (Fig. 1) for fine droplets (Fig. 2). A unique heater technology based on porous metal foam provides a laminar gas flow and guarantees shortest heat up times of the drying gas for very gentle drying condition of heat-sensitive materials. The fine spray dried particles are separated by a novel electrostatic particle collector - a new technology in laboratory scale – for highest particle recovery rates of any kind of material. This new technology is particularly useful where the newest application trends focus on effective formulation of complex and valuable drugs (highly active pharmaceutical ingredients) and nanoparticles. Produce submicron- or even nanoparticles with very narrow size distribution for

new breakthroughs in R&D Invest only a minimal sample amount of high valuable product to receive a dry

powder Profit from minimal loss of high valuable products due to uniquely high yields Safe process time thanks to simple assembling, easy cleaning and fast product

switch

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Figure 1 Figure 2 Poster Session 1 – Contributed Paper

17 EVALUATION OF ITRACONAZOLE ENTRAPPED IN NANOSPHERES OF PLGA FOR THE TREATMENT OF PARACOCCIDIOIDES BRASILIENSIS Elaine P. Cunha-Azevedo, 1; Jaqueline R. Silva1; Marigilson P. Siqueira-Moura2, Anamélia L. Bocca1; Antonio C. Tedesco2; Ricardo B. Azevedo1; 1 Laboratório de Morfologia e Morfogênese, Departamento de Genética e Morfologia, Universidade de Brasília. 2 Laboratório de Fotobiologia e Fotomedicina, Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo. Universidade de Brasília, Campus Darcy Ribeiro, Asa Norte, Brasília, Distrito Federal, 70910-900 Brasil; e-mail contact: [email protected]

The Paracoccidioidomycosis (PCM) is an endemic disease of relevance in Latin America. The current therapy for PCM falls mainly into two classes of antifungals, the triazoles and polienos, such as itraconazole and amphotericin B, respectively. These treatments result in serious side effects for the patients. Various strategies are set to avoid or minimize side effects, and the drug delivery system is one option, promoting a gradual release of the drugs. In this study, an Itraconazole nanoencapsulated technology is applied to the treatment of PCM. The in vitro citotoxicity of hepatocytes and mesangial cells, and antifungical activity, as well as the effectiveness in mice BALB-C infected with Paracoccidiodes brasiliensis of Itraconazole entrapped in nanospheres were evaluated. The citotoxicity was determined by the tetrazolium reduction, MTT assay, after incubation for 24 hours of mesangiais cells and hepatocytes with samples tests (ITZ-NANO- 3 and 6 mg/kg or drug free (ITZ)-50 and 100 mg/kg). The in vitro efficacy of ITZ-NANO to PB was examined and evaluated by minimal inhibitory concentration (MIC) and colony forming units (CFU). For the in vivo studies we did histological examination of the lung of animals infected with 3x107 cells/ml isolated from the fungi Pb18, and treated with either ITZ-NANO- 3 mg/kg or ITZ-50 mg/kg. The concentrations of ITZ-NANO tested in the mesangiais cells and hepatocytes showed

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lower cytotoxicity when compared with ITZ in the same concentration (3 and 6 mg/kg) and also when we used a higher concentration (50 and 100 mg/kg) ( Figure 1). For fungistatic activity against PB, there was no difference for the MIC of cells tretated with ITZ NANOor ITZ. The histopathologic analysis was used to observe the formation of granulomas and the presence of fungal cells in the animals after the treatments. In the group without treatment, both 30 and 60 days, it was observed inflammatory infiltrations, thick lung parenchyma and presence of granuloma and fungal cells. Histological evaluations by using hematoxylin-eosin (HE) showed that the group treated with ITZ-NANO and ITZ showed reduction of inflammatory infiltrate. In the group of animals treated with ITZ-NANO, it was not observed granuloma and also no presence of fungal cells, which was present in lung sections from animals treated with the ITZ (Figure 2). Our results suggest that ITZ-NANO can be a better substitute for the ITZ, since have good efficacy against PB fungi, without side effects apparent.

Poster Session 1 – Contributed Paper

18 HIERACHICALLY NANOSTRUCTURED PARTICLES AS A NANOREACTOR FOR SYNTHESIS OF CORE-SHELL PARTICLES Won San Choi¹, Hye Young Koo², Hye Min Yang¹,³, Ha-Jin Lee¹, Young Boo Lee¹, Tae Sung Bae¹, and Il Cheol Jeon³; ¹Jeonju Center, Korea Basic Science Institute (KBSI), 664-14 Dukjin dong 1-ga, Dukjin-gu, Jeonju, 561-756, Korea; ²Korea Institute of Science and Technology (KIST) Jeonbuk 864-9, Dunsan-ri, Bongdong-eup, Wanju-gun, Jeollabuk-do, 565-902, Korea; ³Department of Chemistry, Jeonbuk National University, 664-14 Dukjin dong 1-ga, Dukjin-gu Jeonju, 561-756, Korea; [email protected]

Hierarchically nanostructured materials having two or more levels of structure have shown unique properties that could not be shown in their bulk counterparts. Their importance has grown by the vast potential applications including chemical reactor, chemical sensor, catalyst, battery, drug carrier, and encapsulation. For this reason, many

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efforts have been devoted to the syntheses and developments of the novel hierarchically structured materials. Herein we report the fabrication method for the extraordinary spherical core-in-shell structures. Our core-in-shell particles were prepared by successive coating of colloidal particles with various kinds of charged materials, and subsequent calcination of the coated colloidal particles. The size of the overall shell and the core could be controlled by using the number of coating. As-prepared, the core-in-shell structures showed excellent ability to prepare core-shell particles composed of a wide variety of materials. Furthermore, we expect that this approach might also be used as a direct method for preparing hierarchical nanoparticles with tailored properties showing individual properties from each other within the single shell. Poster Session 1 – Contributed Paper

19 QUANTIFICATION OF THE ENCAPSULATION EFFICIENCY IN SINGLE SMALL UNILAMELLAR VESICLES AND INVESTIGATION OF VESICLE-DNA INTERACTIONS Brian Lohse, Pierre-Yves Bolinger, Andreas L. Christensen, Dimitrios Stamou; Bio- Nanotechnology Laboratory, Department of Neuroscience and Pharmacology & Nano-Science Center, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark; [email protected]; [email protected]

Encapsulation of water soluble compounds in lipid vesicles is a central problem in the formulation of vesicle based drug delivery vectors but it is also a fundamental step in the use of vesicles as miniaturized bioreactors and for the building of artificial protocells. We report a quantitative study of the encapsulation efficiency (EE) of various water soluble fluorescent markers in single vesicles. Encapsulation efficiency was measured by single vesicle fluorescence microscopy. The single vesicle approach revealed pronounced heterogeneities in EE that were previously hidden due to ensemble averaging. Of particular interest was the observation of an inverse relation between EE and vesicle diameter. Furthermore, we report preliminary work on vesicle encapsulation of DNA and adsorption of DNA to the vesicle membrane. As demonstrated here, single particle analysis is essential for obtaining a detailed picture of the encapsulation process in nanoscale containers. Poster Session 1 – Contributed Paper

20 SINGLE VESICLE ENCAPSULATION AND FUSION: THE DESIGN OF AN ATTOFLUIDIC BIOCHIP Sune M. Christensen, Brian Lohse, Pierre-Yves Bolinger, Nikos S. Hatzakis, Michael W. Mortensen and Dimitrios Stamou, Bio–Nanotechnology Laboratory, Department of Neuroscience and Pharmacology & Nano–Science Center, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen, Denmark; [email protected]

Self-assembled nanocontainers in the form of small unilamellar lipid vesicles (SUVs) have gathered broad interest due to their applications as intelligent drug carriers, as biophysical model membrane systems and as ultra-miniaturised biochemical reaction

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vessels. We investigate single vesicles by arraying intact SUVs on solid supports and probing their properties by fluorescence microscopy techniques, fig. 1a. Here we adopt this single vesicle platform to quantitatively study encapsulation efficiency (EE) of water soluble compounds in SUVs fabricated by standard preparation techniques. The analysis was performed by single particle colocalisation of fluorescence signals of a membrane label and various water soluble probes, fig. 1b. Optimisation of EE is a central problem in all applications of vesicles, especially in the formulation of drug delivery systems. Therefore detailed knowledge of EE is of utmost importance. Our single SUV study revealed two important aspects of EE that was previously hidden due to ensemble averaging: (i) the presence of empty vesicles within SUV preparations and (ii) an inverse relation between EE and vesicle diameter. Furthermore, we demonstrate how biochemical reactions can be conducted inside single SUV containers by mixing aliquots of encapsulated species upon SUV fusion, fig. 1c. We encapsulated the enzyme alkaline phosphatase in one population of SUVs and immobilised them on the surface. In a subsequent step we triggered mixing of the confined enzyme and a substrate (fluoresceine diphosphate) by programmed fusion of the surface coupled vesicles to vesicles in solution. Fusion caused mixing of enzyme and substrate leading to the formation of fluorescent product (fluorescein) within the confined lumen of the surface tethered SUVs. The mixing process was followed by three-channel fluorescence microscopy. We monitored leakage free contents mixing of single SUV pairs that each had a volume on the order of 1 attolitre (10-18 l). Consecuently, we have realised a soft matter based attofluidic system that can be used to quantitatively mix biomolecular species. This systems downscales present state of the art in miniaturisation of fluidic solutions by four orders of magnitude.

Figure 1

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Poster Session 1 – Contributed Paper

21 APPLICATION OF POLYELECTROLYTE CAPSULES IN THE DOMAIN OF TISSUE-ENGINEERING AS CARRIERS FOR GROWTH FACTOR DELIVERY Liesbeth J. De Cock,1 Bruno G. De Geest,1 Stefaan De Koker,2 Sandra Van Vlierberghe,3 Peter Dubruel,3 Filip De Vos,4 Chris Vervaet,1 Jean Paul Remon,1; [email protected] 1Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium; [email protected] 2Department of Molecular Biomedical Research, Ghent University, Technologiepark Zwijnaarde 927, 9052 Zwijnaarde, Belgium

3Polymer Chemistry and Biomaterials Research Group, Ghent University, Krijgslaan 281, Building S4 Bis, 9000 Ghent, Belgium

4Laboratory of Radiopharmacy, Department of Pharmaceutical analysis, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium

The fundamentals of tissue-engineering involve cells, scaffolds and growth factors. Cells synthesize matrices of new tissue, while scaffolds are used as an extracellular matrix. The function of growth factors is to facilitate and promote regeneration of new tissue by cells. A critical point in tissue-engineering is the delivery of growth factors to the site of action. In this project we evaluated the use of polyelectrolyte microcapsules as growth factor carriers, incorporated within synthetic tissue engineering scaffolds. In a first step the possibility to incorporate polyelectrolyte capsules within a synthetic scaffold was evaluated. Therefore, calcium carbonate microparticles (CaCO3) were used as sacrificial templates and coated with 2 bilayers of heparin and poly-L-arginine via the layer-by-layer technique. Subsequently the capsules were added to a solution of methacrylated gelatin, followed by a freezing and thawing cycle to form a porous cryogel. Irradiation of the cryogel with UV light resulted in crosslinking of the methacrylated gelatin. Scanning electron microscopy on whole cryogels and confocal microscopy on sections revealed the successful incorporation of capsules within the cryogel. In a second step it was evaluated whether polyelectrolyte capsules could be loaded with basic fibroblast growth factor (bFGF), a growth factor stimulating proliferation of human dermal fibroblasts. Hollow microcapsules were obtained by the addition of an aqueous disodium ethylenediaminetetraacetate (Na2EDTA) solution to the capsules. Hollow capsules, coated with heparin and poly-L-arginine were loaded with bFGF through electrostatic interaction at slightly acidic pH and low ionic strength, yielding a loading efficiency of 50 %. Upon incubation at physiological pH and ionic strength the growth factor was released in a sustained way over a 7 day period and the amount of released growth factor in the surrounding medium could be controlled by varying the amount of polyelectrolyte capsules. The biological activity of the released bFGF was assessed by adding the bFGF loaded capsules to in vitro cultured human dermal fibroblasts, followed by the evaluation of the cell proliferation at different time points. Compared to fibroblasts incubated with cell medium without growth factor, the cell proliferation was significantly enhanced when bFGF was continuously released from polyelectrolyte capsules. In conclusions, we have demonstrated that polyelectrolyte microcapsules can be efficiently incorporated within a cryogel scaffold. Further we showed that bFGF can be encapsulated and released

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from the microcapsules, resulting in an increased cell proliferation of human dermal fibroblasts. Poster Session 1 – Contributed Paper

22 UPTAKE OF COLLOIDAL POLYELECTROLYTE MULTILAYER CAPSULES BY LIVING CELLS Loretta L. del Mercato1, Pilar Rivera Gil1 , Almudena Muñoz-Javier1,2, Pablo del Pino1,2, Oliver Kreft3, Maximilian Semmling1,4, Susanne Kempter2, Andre G. Skirtach3, Oliver T. Bruns5, Matthieu F. Bédard3, Joahim Rädler2, J. Käs4, Christian Plank2, Gleb Sukhorukov3, Wolfgang J. Parak1,2 1 Fachbereich Physik, Philipps Universität Marburg, Marburg, Germany; [email protected] 2 Universität München, Germany 3 Max-Plank-Institut für Kolloid- und Grenzflächenforschung, Golm, Germany 4 Universität Leipzig, Leipzig, Germany 5 Eppendorf Klinikum, Hamburg, Germany

Uptake and processing of capsules or particles by cells are important issues with regard to the transport of active agents into the cytoplasm. A recently introduced delivery concept of layer-by-layer assembly of thin planar films or spherical geometries of polyelectrolyte multilayer capsules has emerged as a universal carrier system in which cargo and additional functionalities can be introduced as well in the cavities and in the walls of the capsules. Polyelectrolyte multilayer microcapsules functionalized with nanoparticles are ingested spontaneously by cells. Several studies concerning the cellular internalization mechanism of capsules suggest phagosomal/endosomal/lysosomal perinuclear compartments as final locations of the capsules. Although strictly speaking the detailed uptake process of polyelectrolyte capsules by cells remains to be clarified in future studies, some important parameters that regulate this process were elucidated in this work. Polyelectrolyte microcapsules are deformed upon the incorporation process due to the mechanical stress caused in the intracellular space. Deformation was dependent on the structure of the capsule walls. Despite deformation, capsules do not lose their cargo even upon compression inside cells. Regarding the intracellular fate of the capsules, any colocalization with intracellular structures like endosomes or lysosomes was observed. Thus, the results suggest that internalized capsules are trapped in acidic vesicles rather than free in the cytosol. Poster Session 1 – Contributed Paper

23 USE OF DROP-ON-DEMAND NOZZLE FOR MICROPARTICLE PRODUCTION Jiri Dohnal and Frantisek Stepanek, Chemical robotics laboratory, ITC-Prague, Technicka 5 Prague 16628, Czech Republic; [email protected]

One of the key issues of microparticle preparation is the control of particle size distribution. Microparticle preparation by the “wet” technique normally involves mechanical dispersion of two liquid phases and consequently the creation of an emulsion

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by fast stirring. Microparticles prepared using stirring usually have a relatively wide size distribution and the process is difficult to scale up. Our objective is to synthesise microparticles that can be used in controlled release applications for which well defined properties are a key issue. In this work we will present a microparticle fabrication technique based on the use of a Drop-On-Deman print head. This technology can generate small drops with uniform diameter and substitute imperfect mechanical dispersion by stirring. The use of this technology will allow us to produce microparticles with well defined size, morphology and porosity. We have demonstrated that the DOD device can produce uniform droplets in the range of 20 to 60 micrometers (depending on the parameter setting). The resulting microparticle size is then directly proportional to the droplet size and concentration of encapsulating agent. We willl demonstrate the microcapsule preparation on the system Gelatine – Arabic gum since it is widely used by both pharmaceutical and food industry for coacervation of active substances. Poster Session 1 – Contributed Paper

24 FLUORESCENT RATIOMETRIC pH-NANOSENSORS FOR BIODIAGNOSIS APPLICATIONS Tristan Doussineau, Sabine Trupp, Gerhard J. Mohr, Institute of Physical Chemistry, Friedrich Schiller University of Jena, Lessingstrasse 10 D-07743 Jena, Germany; [email protected]

Fluorescent sensors designed in the shape of nanoscaled objects appear as a very promising alternative to the conventional fluorescent probes, i.e. molecular fluorophores, in order to investigate in a non-invasive manner living cells, tissues and microorganisms. Indeed, enhanced brightness and photostability are usually obtained and undesirable cross-reactivity or interferences of the transduction signal prevented. Furthermore, the possibility to tailor the composition and the architecture of these nanosensors enables the concomitant addition of supplementary functions to the nanosensors that foster targeting or drug delivery. A way to design efficient nanosensors is first to embed the indicator dye in polymer nanoparticles. As a consequence, the indicator dye does not interact directly with the biosample reducing the toxicity and preventing cross-reactivity with proteins. Additionally, it is possible to embed together with the indicator dye a reference dye thus giving reliable ratiometric measurements for continuous analyte monitoring in biosamples. In this communication, results on the design of pH-nanosensors with core-shell architecture will be presented. The first system consists of zeolite beta cores embedding a flavone dye as a reference and a silica shell containing the pH-sensitive fluorescein. A second system will be described consisting of amorphous silica cores containing a rhodamine dye and immobilized pH-sensitive naphthalimide derivatives in the shell. Morphological and optical properties will be shown. Both types of nanosensors exhibit a pKa suitable for bioanalytical investigations.

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Poster Session 1 – Contributed Paper

25 INTERFACIAL RHEOLOGY OF SURFACE-ACTIVE BIOPOLYMERS: GUM ARABIC VS. HYDROPHOBICALLY MODIFIED STARCH Philipp Erni1, Alan Parker1 and Peter Fischer 2 1Firmenich SA, Corporate Research Division, CH-1217 Meyrin 2, Geneva, Switzerland; 2Institute of Food Science & Nutrition, ETH Zurich, 8092 Zurich, Switzerland; email: [email protected]

Gum Arabic is a dried plant exudation obtained from the stems and branches of Acacia senegal or Acacia seyal. We study the interfacial rheology of gum Arabic at air/water and oil/water interfaces both in shear and dilatational deformations. For shear flow experiments, we use a biconical disk interfacial rheometer. In compression/dilatational mode, relaxation and oscillation tests are performed in a Langmuir film balance and with a pendant drop device. The results are compared with identical experiments performed with adsorbed layers of hydrophobically modified starch, a common substitute for Acacia gum. In dilatational deformations, the viscoelastic response of modified starch is similar, but slightly weaker as compared to Gum Arabic. In contrast, we found a very different behavior in shear flow: for gum Arabic a gel or glass-like network with dominant interfacial storage moduli and a linear viscoelastic regime limited to small shear deformations is observed. On the other hand, the films formed by modified starch are predominantly viscous and the shear moduli less dependent on the deformation. The dynamic interfacial responses also imply different stabilizing mechanisms for acacia gum and modified starch: gum arabic produces strong, viscoelastic interfacial films, whereas modified starch acts as a more ‘traditional’ polymeric surfactant. Poster Session 1 – Contributed Paper

26 NOVEL PARAMAGNETIC MIXED MICELLES AS POTENTIAL MRI CONTRAST AGENTS Chiara Giannachi*, Simonetta Geninatti Crich†, Claudia Cabella*, Chiara Francisco, Roberta Cavalli‡, Alessandro Maiocchi*; *Bracco Imaging S.p.A., Centro Ricerche Bracco, Bioindustry Park del Canavese, Via Ribes 5, I-10010 Colleretto Giacosa (TO); † Center for Molecular Imaging, University of Torino, via Nizza 52, Torino 10126; ‡ Department of Drug Science and Technology, University of Turin, Torino 10125, Italy; [email protected]

Magnetic Resonance Imaging (MRI) is one of the most important non-invasive imaging modalities in clinical diagnostics and preclinical research. The success of MRI is due to the ability to image tissues with high resolutions in three dimensions, routinely down to 1 mm at clinical field strengths. However, MRI suffers from an intrinsic insensitivity with respect to the competing imaging modalities such as Nuclear Medicine and Optical Imaging. This limit can be overcome by using nanosized carriers that can deliver huge payloads of imaging reporters at the targeting site. Paramagnetic micelles have often been considered as nanosized contrast agents for MRI applications. To this end, several Gd(III) complexes bearing lipophilic substituents have been reported. These molecules form

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aggregates in which the hydrophobic portions are oriented within the cluster and the hydrophilic moieties (containing the Gd-probe) are exposed to the solvent. These systems mainly act as T1-relaxation agents, whose efficiency is eventually enhanced by the long reorientational time of the supramolecular aggregate. The objective of this work is the design and preparation of paramagnetic micelles based on B22286, a highly stable lipophilic Gd(III) complex synthesized in our laboratories. We evaluated three different techniques for the preparation of the mixed micelles as follows: thin layer-evaporation method, solvent-emulsification and diffusion method and solvent injection technique. For each method, different surfactants/co-surfactants combinations were explored obtaining the best formulations with the solvent injection technique. With this method, we produced stable monodispersed mixed micelles with an average size lower than 100 nm. Interestingly the formulation of B22286 as micellar system requires the presence of a short and symmetric alcohol acting as co-surfactant in combination with a non ionic surfactant. All the produced micelles were characterized measuring their size, polydispersion index and the zeta potential. For the most promising formulations the physico-chemical characterization was also extended to their relaxometric properties. In particular the best mixed micelles formulation shows high relaxivity values (r1 and r2) at any magnetic field in the range of those applied in the clinical practice. Furthermore using some relaxivity measurements we were able to demonstrate the stability of these mixed micelles in several media. For the above reasons we believe that the new mixed micelles formulation of B22286 has the potential to become a suitable nanoprobe for MRI applications. Poster Session 1 – Contributed Paper

27 MICROENCAPSULATION OF BIOLOGICAL OBJECTS WITH CELLULOSE SULFATE Kay Hettrich1, Wolfgang Wagenknecht1, Bert Volkert1, Brian Salmons2, Walter Günzburg2,3 1Fraunhofer Institute for Applied Polymer Research (IAP), Geiselbergstr. 69, D-14476 Potsdam-Golm, Germany, [email protected]; 2SG Austria Pte Ltd, 20 Biopolis Way 05-518 Centros, Singapore 138668; 3 Institut of Virology University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210 Vienna, Austria

Cellulose sulfate have so far received rather small attention within cellulose derivatization reactions, as compared, for example to acetylation or nitration. Although sulfated polysaccharides like heparin or agar[-agar] with certain properties are encountered in nature. The synthesis of cellulose sulfate can be occurred by heterogeneous, homogeneous or quasi-homogeneous process. The transition from a two-phase to a one-phase system during the reaction is understood as quasi-homogenous process. Cellulose sulfates with defined properties can be formed applying the discussed three different routes for synthesis. Important characteristics of cellulose sulfates regarding their applications are solubility (e.g. in water), rheological behavior, different interaction with low or high molecular cations, thermo reversible gel formation, enzymatic degradability, anticoagulant and antiviral activity. Regioselectivity of substitution within the AGU is relevant with regard to application of cellulose sulfate in the biomedical field. A simultaneous acetylation and sulfation of cellulose with acetic

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anhydride and chlorosulfuric acid lead to a substitution of cellulose in C-6-position after saponification of the acetyl groups. For the micro-encapsulation of biological objects e.g. living cells for clinical applications suitable sodium cellulose sulfate should be substituted regioselectively in C6 position with a DS between 0.3 and 0.7. The use of cell encapsulation is a concept with an enormous clinical potential for the treatment of a wide range of diseases. The principle is to develop an artificial, semi-permeable capsule with sufficient permeability that nutrients and oxygen can reach the cells, and appropriate cellular products can be released into the blood stream or to adjacent tissues. At the same time, the capsular material must be restrictive enough to exclude immune cells and antibodies that would cause rejection and destroy the implant. The encapsulated product can thus be viewed as a device that allows transplantation without the need for immunosuppression. A wide range of cells and cell lines (allogeneic or xenogeneic, primary established or genetically modified) may be enclosed within semi-permeable and biocompatible immobilization polymer materials. Poster Session 1 – Contributed Paper

28 MOLECULARLY IMPRINTED NANOPARTICLE-ON-MICROSPHERE CHIRAL CINCHONA-POLYMERS FOR THE ENANTIOSELECTIVE-CONTROLLED DELIVERY OF RACEMIC OMPRAZOLE Chutima Jantarat1, Sarunyoo Songkro1, Helmut Viernstein2, Wolfgang Lindner3 and Roongnapa Srichana1, 1The NANOTEC Center of Excellence and Drug Delivery System Research Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai, Songkla Thailand 90110, 2Institute of Pharmaceutical Technology and Biopharmacy, 3Institute of Analytical Chemistry and Food Chemistry University of Vienna, Vienna, Austria 1090; [email protected]

Molecularly imprinted polymers (MIPs) have been investigated as a convenient means of creating three-dimensional networks with a cavity capable of memorizing the shape and functional group position complementary to the template molecule. The ability of imprinted polymers to bind a template molecule with high affinity lends to their application as excipients for sustained drug delivery. The potential use of MIPs in enantioselective-controlled delivery has been demonstrated for chiral drugs. In the current study, the S-omeprazole molecularly imprinted polymer (MIP) nanoparticle-on-microsphere (NOM) with chiral cinchona functional monomer anchors have been successfully prepared, using suspension polymerization involving agitation of the reaction mixture at high speed. The integration of the MIP-NOM into a self-assembled porous cellulose membrane allowed a controlled distribution and availability of the molecular recognition sites within a porous structure. The nature of the membrane-included microparticles determined the degree of porosity whilst the adherent nanoparticles provided an increased surface area enabling the composite membrane to be employed efficiently for the transmembrane transport of the S-omeprazole imprinted molecule. In this study, These newly developed MIPs have been used to design delivery systems for the partial selectively release of omeprazole enantiomers from racemic omeprazole, in which NOM-MIP was encapsulated within a pH-responsive polymer of the matrix. The prepared delivery systems have been characterized in vitro release studies. The results demonstrate that the drug delivery system containing S-omeprazole

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imprinted cinchona-polymer may have the potential for maximizing efficacy while minimizing dose frequency and toxicity. Poster Session 1 – Contributed Paper

29 PRODUCTION OF HOLLOW CARBON MICROPARTICLES FROM BIOMASS RESOURCES Katsumi Kamegawa, Masaya Kodama, Tsuyoshi Sakaki, Kinya Sakanishi, Keiko Nishikubo, and Yoshio Adachi, National Institute of Advanced Industrial Science and Technology, 870-1, Shuku-machi Tosu, Saga 841-0052 Japan; [email protected]

Carbon black, a typical carbon nanoparticle, is manufactured by pyrolyzing heavy oil (fossil resources) at about 1500oC. It is used mostly as a raw material for tires. Conversion of heavy oil consumption to the use of biomass (renewable biological resources) is demanded to retard global warming and to preserve limited fossil resources. Lignin is an abundant biomass resources and are produced as a by-product of paper manufacturing. For the present study, we have examined production of carbon microparticles from lignin. The preparation procedure of carbon microparticles consists of rapid drying of a mixed solution of lignin and inorganic salts using a spray dryer, pyrolysis of the composite particles at 700oC in nitrogen, washing of the pyrolyzed product with water, and drying at 120oC. Four representative forms of carbon microparticles are presented in the figure: (a) high-strength and lightweight carbon microshell with a thick shell (size, 0.3–5 µm; bulk density, 0.3 kg/L), (b) extraordinarily lightweight carbon microballoon with a very thin shell (0.3–5 µm, 0.01 kg/L), (c) carbon nanobead (10–200 nm) resembling carbon black particles, and (d) hollow carbon nanoshell (3–30 nm) incorporated mutually in a spongy carbon shell. The inorganic salts dissolving in water were reused after selective removal of contaminants from lignins by addition of appropriate agents and separation of resulting precipitate. Because the carbon microparticles from biomass are lightweight materials and show high surface areas, it is expected that they will be most useful in such applications as a reinforcing agent for rubber, a lightweight filler, activated carbon, toner, an anti-electrostatic agent, and a battery electrode material.

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Poster Session 1 – Contributed Paper

30 POLYELECTROLYTE NANO-ASSEMBLED MICROCAPSULES FOR BIOSENSING OF GLUCOSE IN HUMAN SWEAT David Haložan 1,2,3, Georg M. Guebitz 4, Gleb B. Sukhorukov 5, Helmuth Möhwald 3, Vanja Kokol 2 1* Institute for Physical Biology, Toplarniška 19, SI-1000 Ljubljana, Slovenia; [email protected] 2 Institute of Engineering Materials and Design, University of Maribor, Smetanova ul. 17, SI-2000 Maribor, Slovenia; [email protected] 3 Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, D-14476 Potsdam/Golm, Germany 4 Department of Environmental Biotechnology, Graz University of Technology, Petersgasse 12, A-8010 Graz, Austria 5 Department of Materials, Queen Mary University of London Mile End Road, London, E1 4NS, United Kingdom

The new biocompatible and antiallergic approach to detect selected human sweat ingredients as glucose, important for evaluation of human physiological and metabolic conditions, was implemented by using suitable enzymes, which are able to transfer selected sweat substrates to optically detectable submicron products. Today the glucose determination apparatus are widely used in common life, medicine and pharmacology. Commercially available sensors are frequently used for detection and determination of glucose concentration in macroscopic range. Our aim was to develop and assemble a submicrometer polyelectrolyte microcapsule sensor that would increase the lower sensitivity for glucose and would be capable of measuring glucose concentration above 200 mM with linear response. The enzyme’s optimal substrate activity was studied in the polyelectrolyte LbL (Layer-by-layer) assembled microcapsules for being able to exchange analyte with outer measuring environment, i.e. human sweat. For that purpose GOX and HRP were encapsulated and immobilised in microcapsules with suitable enzyme substrate, o-dianisidine or guaiacol. The efficacy of encapsulated enzymes was determined by fluorescence spectra measurements using partially labelled enzymes with fluorescence dyes, while the glucose detection was evaluated by UV/Vis photospectroscopy for various reaction times (0 to 11 minutes) at 35 oC and depending on the concentration of glucose and volume of administrated sample. Diffusion of glucose from the bulk sweat solution through semipermeable polyelectrolyte microcapsule wall into inner microcapsule enzyme solution was taken into account. Small ions are distributed between inner and outer solution according to well known Donnan distribution due to their concentration and presence of big nonpermeable macroions. The variation in pH and salt concentrations in human sweat, depending on different skin glands secretion in specific parts of the body, was also considered. This research has been supported by a Marie Curie Transfer of Knowledge Fellowship of the EC FP6 (contract No. MTKD-CT-2005-029540-POLYSURF) and the Slovenian Research Agency (Grant No. Z2-9623).

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Poster Session 1 – Contributed Paper

31 SYNTHESIS AND CONTROLLED RELEASE CHARACTERISTICS OF HOLLOW SiO2 MICROPARTICLES Pavel Kovačík, Aleš Zadražil and František Štěpánek, Department of Chemical Engineering, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague, Czech Republic; [email protected]

The aim of this work is to fabricate hard porous micro-particles based on silica (SiO2) to create bodies of so-called chemical robots. Porous SiO2 shells or micro-skeletons are ubiquitous in nature – in particular in mari1303853ne microorganisms (diatoms). It is envisaged that a chemical robot will be a simple fully synthetic “unicellular organism”, with main attributes similar to those of living organisms, such as the ability to move in its environment, exchange matter with its surroundings or accumulate or excrete reaction products, except reproduction and evolution. The size range of the micro-particle entities will be in order of 10-100 µm. There are several methods how these particles can be prepared such as self-assembly of colloidal particles to form the so-called colloidosomes or precipitation of silica around a template. The latter method was used for creating porous micro-particles in this work. The procedure based on the Störber method was used for preparing hollow silica micro-particles. The hollow core was obtained by a sol – gel process of tetraethyl orthosilicate (TEOS) in non-ionic W/O emulsion containing kerosene, sorbitan monooleate (Span80) and water. The second way is to use micro-particles as a template (sodium hydrogen carbonate, calcium carbonate, polystyrene beads) which is subsequently removed to create hollow core. The experimental conditions affecting the micro-particles properties (size, thickness, permeability) were investigated in order to precisely control characteristics of the chemical robot body. We will show that particle size can be systematically varied in the range of 10 – 100 µm and that the shell thickness can be changed independently of the core diameter. The particle size distribution was measured by the laser scattering method and the microstructure of the porous particles was visualized by SEM and x-ray microtomography. The permeability of the silica shell was characterized indirectly by measuring the uptake/release kinetics of a model substance (vitamin B12, methylene blue) using UV/VIS spectrophotometry. Strategies for further modification of the properties of the porous shell (control of porosity, pore size distribution, surface properties) will be discussed. Poster Session 1 – Contributed Paper

32 NANOBIOTECHNOLOGICAL POTENTIAL OF S-LAYER COATED LIPOSOMES 1Seta Küpcü, 2Monika Vetterlein, 1Andrea Scheberl, 1Bernhart Schuster, 2Margit Pavelka and 1Uwe B. Sleytr 1Department for Nanobiotechnologie, University of Natural Resources and Applied Life Sciences, Gregor-Mendel Strasse 33, 1180 Vienna, Austria 2Department of Cell Biology and Ultrastructure Research, Center for Anatomy and Cell Biology, Medical University of Vienna, Schwarzspanierstr. 17, 1090 Vienna, Austria

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Crystalline S-layer proteins occur as outermost cell envelope component in many bacteria and archaea. Isolated S-layer subunits are composed of a single protein or glycoprotein species with the ability to self-assemble into well defined nanolattices on planar and spherical surfaces (e.g. glass, silica, gold, lipid layers). These properties make S-layer protein to ideal building blocks for nanomaterials which can be used for nanopatterning of lipid vesicles including liposomes, emulsomes and lipid-plasmid complexes which resemble an artificial virus envelope. Beside the thermal and mechanical stabilizing effects of the S-layer lattice on liposomes the S-layer lattice represents a surface with a broad functionalization potential. Chemical and genetical methods are applied for functionalization of S-layer proteins which opens new ways for creating side specific and biocompatible surfaces for targeting and delivery systems. Methods for recrystallizing isolated S-layer subunits from different bacteria strains on liposomes have been established. Recrystallization conditions have been optimized for each distinct S-layer protein in terms of ion content of the recrystallization solution and lipid composition of the liposomes. Liposomes coated with S-layer subunits of Lysinibacillus sphearicus CCM2177 exhibit p4 lattice symmetry with a zeta-potential value of -26 mV whereas with S-layer subunits of Geobacillus stearothermophilus PV72/p2 coated liposomes are exhibiting p1 lattice symmetry and a zeta-potential of 23 mV. These data demonstrate that a basic surface manipulation of liposomes can be induced by the different physicochemical properties of various S-layer proteins. It is a challenge to investigate the behaviour of S-layer coated liposomes with and within eukaryotic cells. Uptake of S-layer coated liposomes is investigated by fluorescence- and electron microscopy. For these studies the liposomes were loaded prior S-layer protein recrystallization either with hydrophilic or lipophilic fluorescent dyes or electron dense macromolecules were entrapped for visualizing the liposomes by electron microscopy. Internalization of such liposomes is investigated in various human cell lines in cell culture. The endocytic pathway of S-layer coated liposomes could be demonstrated by fluorescent labelling of cell compartments such as early endosomes and lysosom. Furthermore, the application of liposomes coated with fluorescent S-layer-fusion proteins is another promising approach to study their location in cell compartments. Thus, S-layer coated liposomes constitute very usefull tools not only for elucidating the uptake by eukaryotic cells but also for the production of new targeting and delivery and systems. Poster Session 1 – Contributed Paper

33 ELECTROHYDRODYNAMIC JETTING OF POLYMERS USING CO-AXIAL NOZZLES Min Young Kim, Hwanki Ho, Chul Ho Park, SaeHyun Park, and Jonghwi Lee; Chung-Ang University; 221, Heukseok-dong, Dongjak-gu; Seoul, 156-756, Korea (South); [email protected]

Electrohydrodynamic jetting has been used to prepare fibers (electrospinning) and particles (electrospraying). This process uses electrostatic force applied on the surface of jetting solution to drive hydrodynamic driving force for jetting. Chitosan is difficult to electrospin due to their lack of chain entanglement. The concentration of chitosan solution for spinning cannot easily be increased due to its high viscosity. A concentration above 3% became gelled, and below 2% only particles were prepared. Thus, it was

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reported that fibers could not be prepared from electrospinning of chitosan in aqueous acetic acid. Instead of pure chitosan, a mixture of chitosan and another polymer was tried to prepare fibers for drug delivery and tissue engineering applications. In this study, without using an extra polymer, pure chitosan fibers were prepared from electrospraying. Electrospraying produced well dispersed chitosan nanoparticles and encapsulation particles, and subsequent processes assembled them into fiber structures. The fiber formation sensitively relies on various processing parameters such as type of dispersing medium for nanoparticles, concentration of chitosan, etc. The fibers did not show any significant stretching of chain molecules in the examination of SEM and XRD. This processing technique can be used for the fiber formation of polymers difficult for electrospinning. Poster Session 1 – Contributed Paper

34 POLYMER-DIRECTED CRYSTALLIZATION OF ATORVASTATIN Hyemin Choi, SaeHyun Park, Min Kyung Lee, and Jonghwi Lee; Chung-Ang University; 221, Heukseok-dong, Dongjak-gu; Seoul, 156-756, Korea (South); [email protected]

Polymer directed crystallization has been investigated to understand biomineralization process in nature and produce organic/inorganic hybrid materials with complex morphologies. The existence of polymer induces crystal face-selective polymer adsorption and mesocrystal formation, resulting in unique hierarchical materials with structural specialty and complexity, and a size range spanning from nanometers to micrometers. Crystallization of drug compounds has been an important issue, because it determines drug bioavailability, stability, processability, etc. However, the polymer-directed crystallization technique has seldom been applied to the crystallization of drug compounds. Herein, the crystallization conditions for maximizing the interactions between polymers and drugs were examined, and the effect of various polymers on the crystallization of atorvastatin was studied. Atorvastatin/polymer mesocrystals and their composite encapsulation particles were successfully obtained using the polymer-directed crystallization technique. The adsorption layer of polymer and stabilized mesocrystals of atorvastatin produced interesting properties. The results proved that the polymer-directed crystallization technique could be useful in the pharmaceutical research and development. Poster Session 1 – Contributed Paper

35 MULTI-FUNCTIONAL POLY UREA FORMALDEHYDE CAPSULES Dennis Lensen1,2, Joost Opsteen1, Margot Segers2, Dennis Vriezema1 and Jan van Hest2; 1Encapson B.V., Toernooiveld 1, Nijmegen, 2Organic Chemistry, Institute for Molecules and Materials, Radboud University Nijmegen, Heyendaalseweg 135, Nijmegen; [email protected]

In the last decades, several methods have been utilized to form microcapsules, which are used as e.g. biosensors, drug delivery vehicles, nanoreactors or self healing materials. Here we describe the formation of poly urea formaldehyde capsules via precipitation polymerization and two applications in the field of biomedical devices: first capsules for self healing bone cement and second, magnetic capsules for guided imaging.

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Poster Session 1 – Contributed Paper

36 DOUBLE CONTROLLED RELEASE FROM HYBRID MATERIALS CONTAINING MICROSPHERES AND HYDROGELS Madarieta I. Pardo, Sáez V. Martinez, Olalde B. Graells and *Garagorri N. Gantxegi; Health Unit of INASMET-TECNALLIA. Mikeletegui Pasealekua, 2. Technological Park. 20009 San Sebastian. Spain; [email protected].

The development of release systems capable of delivering drugs over extended period of time is deemed desirable for a variety of biomedical applications. The goal of this work was to create hybrid materials with different release profiles. For such purpose, materials were obtained by dexamethasone loaded PLGA-Microspheres photoencapsulation in the polymer meshwork of a poly (ethylene glycol) hydrogel. Microspheres of 30-40µm and 2-3µm in diameter were assayed alone and in combination with the hydrogel. The microspheres showed an optimal morphology visualized by SEM and the loading amount of dexamethasone ranged from 65-118µg/mg and 40-50µg/mg respectively. Dexamethasone release was studied from the microspheres, hydrogels and from the hybrid materials. The non degradable hydrogel drug release showed an initial burst followed by a release at a significantly low amount with the 98% of the drug released in the first three days. PLGA microspheres controlled the release at least for two months with a final cumulative release of 85% in 57 days for the 30-40 µm particles and 90% in 15 days for the 2-3 µm particles. The embedding of the microspheres in the hydrogel network controlled again the release which was attenuated in a 15-25% and 50% for each type of microsphere respectively. Since their localized and more sustained release of the drug, these hybrid materials present promising opportunities for the design of anti-inflammatory drug delivering biomaterials.

Poster Session 1 – Contributed Paper

37 MICROENCAPSULATION BY COACERVATION OF BIODEGRADABLE POLYMER WITH THYME OIL Isabel M. Martins, Sofia N. Rodrigues, Filomena Barreiro and Alírio E. Rodrigues; LSRE – Laboratory of Separation and Reaction Engineering, Department of Chemical Engineering, Faculty of Engineering of University of Porto, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal; [email protected]

Microcapsules of polylactide (PLA) were produced by coacervation to encapsulate the antioxidant and antimicrobian agent - essential oil of Thymus Vulgaris L. (thyme oil). Biodegradable microcapsules of polylactide have received extensive attention as delivery systems for drug encapsulation. This type of biodegradable polymeric carriers can be hydrolyzed in the body to form products that are easily resorbed or eliminated. The core material, thyme oil, is an aromatic and medicinal plant of increasing economic importance for North America, Europe and North Africa. This essential oil is used in the flavour and food industries. As pharmaceutical, the oils thymol and carvacrol are used in mouthwashes, soaps and creams. The thyme oil is also used in manufacture of perfumes and cosmetics.

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The objective of this work is to develop a novel coacervation process to produce microcapsules of PLA to encapsulate thyme oil that will be used in cosmetics. PLA is soluble in organic solvents but insoluble in water. Generally, PLA is used to encapsulate water soluble active principles such as drugs, pesticides and dye-stuffs by coacervation, mainly by means of microspheres production or by using double emulsion techniques (o/w/o). However, the objective of this work is to encapsulate thyme oil, a water insoluble active principle that needs, in a first step, the preparation of an oil-in-water emulsion. The novelty of our process consists on dissolving PLA in dimethylformamide (DMF) which is a good solvent for PLA but in addition has high solubility in water. Upon contact with water, the homogeneous solution of PLA in DMF, promotes the precipitation of PLA around the thyme oil core. With this work we demonstrate a new, easy and executable method of coacervation by introducing modifications on microencapsulation process that allow the encapsulation of an oily active principle by simply preparing an o/w emulsion. Control of size and wall thickness of microcapsules, encapsulation efficiency, the influence of surfactants and release of thyme oil were studied. The produced microcapsules have bimodal particle size distributions in volume with a mean particle size of 40 µm. Microcapsules analysis by microscopy have confirmed the spherical shape, the rough surface, and allowed the estimation of the wall thickness around 5 µm. Quantification of the encapsulated thyme oil was performed by gas chromatography and allowed to evaluate the quality of the encapsulated oil and pointed out for a preferential encapsulation of thyme oil apolar compounds.

Poster Session 1 – Contributed Paper #

38 MAGNETIC NANOPARTICLES FOR GENE DELIVERY: SOME DETERMINANTS OF EFFICIENT DELIVERY VECTORS Olga Mykhaylyk, Yolanda Sanchez-Antequera, Nittaya Tresilwised, Elena Oranskaya, Anna Slawska-Waniewska, Stefan Thalhammer, Denis Adigüzel, Markus Döblinger, Thomas Bein, Per Sonne Holm, Zygmunt Pojda, Christian Plank. Klinikum rechts der Isar, Institute of Experimental Oncology and Therapy Research, Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany, [email protected]

About thirty magnetic nanoparticles of the core-shell type comprising magnetite cores of about 10 nm stabilized and decorated by self-assembly of surfactant and polymers to be suitable as components of magnetic nucleic acids delivery vectors by magnetofection and their formulations with nucleic acids and adeno- as well as lentiviral particles were screened for their gene delivery efficiency in vitro. The group of the most efficient particles was defined and characterized with respect to their core composition, crystallite size, magnetization, coating composition using TEM, XRD, magnetization and XPS methods. Magnetic gene delivery formulations were optimized with account for the association of DNAs, siRNAs and adeno- and lentiviral particles with magnetic nanoparticles. A simple method for evaluation of the magnetophoretic mobility and, hence, of the magnetic moment was used to characterize the complexes and evaluate the number of magnetic nanoparticles associated with complexe(s). Together with TEM and AFM data, these approaches

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deliver information on the morphology, composition and magnetic properties of the complexes which are important for identifying the most efficient magnetic vectors. The developed transfection protocols can be used for cells that are difficult to transfect, such as primary cells, and can also be applied to improve significantly viral nucleic acid delivery. With minor alterations, these protocols can also be useful for magnetic cell labelling for cell tracking studies. Specifically, we were interested in how physico-chemical and surface characteristics of iron oxide magnetic nanoparticles and their complexes with adeno- and lentiviruses correlate with the infectious potential in target cells. We have shown that magnetofection of oncolytic adenovirus does not alter the inherent oncolytic potential of the virus but that it rather enchances virus uptake into cells. Optimized assembling with selected magnetic nanoparticles lowers the IC50 of the adenovirus in 181RDB cells and lentivirus in umbical cord mesenchymal stem cells one order of magnitude. We suggest a “rule” to formulate virus magnetic complexes based on our fine-tuning of the nanoparticles-to-virus particles ratio in the range of 2.5-20 fg iron per physical virus particle depending on the nanomaterial used. We show also that an excess of magnetic nanoparticles can inhibit infection efficiency. The figure shows an atomic force microscopy 3D image and a contour plot of adenovirus associated with magnetic nanoparticles. The average size of the complexes is 171±17 nm. Taking into account that rather poor information is usually available on the structure and composition of the commercial magnetic nanomaterials, we hope that our published protocols on synthesis of magnetic nanoparticles, their thorough characterization, formulation of the plasmid, siRNA magnetic delivery vectors could enable further progress in the field. General Session 3 – Keynote Paper

39 INDUSTRIAL ENCAPSULATION PROCESSING Ronald J. Veršič, Ronald T. Dodge Company, 55 Westpark Road, Dayton, Ohio 45459-4812 USA; [email protected]; [email protected]

Many microencapsulation processes have been describe in the literature for over 50 years now. But very few are in actual, large-volume, industrial practice. Examples are spray drying, urea-formaldehyde and its many variations, and coacervation. The presenter describes those few, chosen processes and then illustrates the reasons why they have been selected from the innumerable candidate processes. Actual industrial products (non-pharma) are used to illustrate each process. Finally, a methodology is suggested on how to discover and invent new processes. General Session 3 – Invited Paper

40 LIQUID-CORE MICRO AND NANO-CAPSULES FOR THE EXTRACTION OF DRUGS AND PESTICIDES/HERBICIDES Ian Marison and Michael Whelehan, School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland; [email protected]

The presence in drinking water of commonly used medication for humans and animals (drugs) and pesticides/herbicides used in agriculture, represents a major health hazard. This is partly due to the techniques currently used in the water industry being unable to efficiently remove or breakdown the compounds. Many of these compounds are relatively poorly soluble in water and/ or have a high partition coefficient when placed in

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an octanol water mixture (logP) and are therefore termed hydrophobic organic pollutants (HOPs). As a result liquid-liquid extraction may be used to remove such compounds, however the large quantities of the solvents required, combined with need for high power requirements for mixing, their toxicity and difficulties in phase separation mean that this is not a viable method. In order to address this issue, and overcome the problems with liquid-liquid extraction, we have developed liquid-core microcapsules in which the organic solvent is surrounded by a hydrogel membrane The vibrating nozzle technique, using a concentric nozzle system combined with electrostatic jet break-up, was used to produce monodisperse microcapsules with diameters below 800µm. Such microcapsules were shown to efficiently remove a range of drugs, including carbamazepine, clofibric acid, warfarin, diclofenac as well as a range of commonly found pesticides/herbicides, including atrazine and 2,4-D. Interestingly, the rates and levels of removal of the compounds was not a simple function of their logP. Consequently microcapsules were prepared with different solvents within the cores and combined to enable complete removal of mixtures of the compounds. The resulting microcapsules containing the HOPs were shown to be re-usable by either back-extracting the compounds from the cores and/or by biological breakdown using Pseudomonas sp. Preliminary experiments have been carried out with self-assembling liquid-core nanocapsules and shown to be even more efficient at removal of the HOPs, with extraction times of seconds compared with minutes for the microcapsules. In a further development of this extraction technology (capsular perstraction), the liquid-core microcapsules have been developed for use in the pharmaceutical industry. An example is the microbial production of the antibiotic and anti-cancer compound geldanamycin (GM). This fermentation is currently un-economic due to product inhibition as well as the instability of GM under the production conditions. By addition of sterile liquid-core microcapsules to the fermentation medium, the GM could be removed at a rate faster than that of the production rate resulting in higher production yields and long term stability. General Session 3 – Invited Paper

41 DEGRADABLE POLYELECTROLYTE MICROCAPSULES FOR BIOMEDICAL APPLICATIONS Bruno G. De Geest, Stefaan De Koker, Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium; [email protected]

Polyelectrolyte capsules have emerged as novel drug delivery systems which hold potential for the delivery of macromolecular drugs to phagocyting cells. These capsules are fabricated by layer-by-layer coating of a sacrificial template followed by the dissolution of the template resulting in a hollow capsule. Macromolecules can be encapsulated within the capsules’ hollow void using a template pre-loaded template or by post-loading by reversible switching the permeability capsules’ membrane . The main advantages of these capsules are (1) their multifunctionality which allows to incorporate a wide variety of species (such as e.g. synthetic polymers, proteins, nucleic acids, lipids, nanoparticles, etc…) both in their hollow void as well as their membrane which allows one to equip the capsules with different bio-active properties, (2) the ability to tailor their physicochemical properties to the nanoscale by varying the capsules size, shell thickness and shell constituents and (3) their easy of preparation under mild

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all-aqueous conditions without the sue of organic solvents, reactive chemistry or high shear forces which are often employed in traditional micro-encapsulation protocols. Here we present degradable polyelectrolyte capsules and show their potential as antigen delivery vehicle for antigen delivery. We assed the cellular uptake and antigen processing and presentation by dendritic cells in vitro and went further in vivo to elucidate the induced immune response after both subcutaneous and pulmonary delivery. We show that by varying the capsules’ surface chemistry the type of immune response can be tailored and finally we demonstrate protective immunity in a melanoma tumour model. General Session 3 – Invited Paper

42 FRAGRANCE ENCAPSULATION IN MICRO AND NANOPARTICLES Christian Quellet, Givaudan Schweiz AG, Ueberlandstrasse 138, CH-8600 Dubendorf, Switzerland; [email protected]

Microencapsulation has become a mature technology within the fragrance industry and several microencapsulated products are now found in the market place, such as spray dried powders and core-shell “scratch and sniff” aminoplast microcapsules. Alternatively, plain (or matrix) particles offer interesting diffusion-driven release patterns, which can be controlled by controlling the structure of the particle, the nature of the matrix materials and the selection of the fragrance molecules to be encapsulated. In this presentation, the major scientific and technical challenges underlying the encapsulation of fragrances in diffusive particles are reviewed, emphasizing both thermodynamic and kinetic aspects. The advantages and disadvantages of nano-encapsulation compared to micro-encapsulation are also reviewed in the specific context of matrix particles. General Session 4 – Invited Paper

43 MANUFACTURING MICROCAPSULES FOR ADVANCED MATERIALS Thorsten; Brandau, Egbert, Strohm, Holger; BRACE GmbH, Taunusring 50, D-63755 Alzenau, Germany; [email protected]

Applying vibrating nozzle processes for the production of microspheres and microcapsules has a lot of advantages when compared to other methods: Vibrating nozzle processes render it possible to produce particles with a monomodal grain size distribution and a single sharp maximum. dmax/dmin-values lower than 1.10, 1.05, or even 1.01 are customary for spherical granules produced with a vibrating nozzle microsphere unit designed by BRACE (see Figure 1). BRACE microspheres are solid spheres with a matrix-encapsulated active agent whereas BRACE microcapsules consist of a solid shell and a liquid or solidified core. These two types of microgranules differ mainly in their release profiles: Microspheres usually show diffusion controlled release profiles with a permanent release rate that is controlled kinetically by means of the particle size, whereas microcapsules expel their content with a single burst as the shell breaks. On the other hand, microcapsules may exhibit extremely slow release rates when appropriate materials are used. Various applications have shown that microspheres produced with laminar flow breakup

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processes have many advantages compared to classical preparation methods as spray-drying or spray-cooling. Due to the laminar nature of the flow, no sudden demixing processes occur when the flow is exiting the nozzle. Since the processes lead to monomodal size distributions, no polymorphisms occur. A truly controllable controlled release profile can therefore be designed by manipulating only one process parameter (particle size) instead of various ones such as load, size, drying rates etc. By applying the double nozzle process for the production of core-shell microspheres, new materials with exiting properties can be obtained. These "real" capsules can be designed to release their contents with a burst as soon as the capsule becomes subject to low pressure, or to release their contents extremely slowly over a long time. Therefore, it becomes possible to provide solutions for both flavour chemistry and textile applications. Since the processes are easily up-scalable, the retesting and scale-up time from laboratory-size to production-size throughputs is short. Usually, a production unit runs with the same feed compositions and the same parameters as the desktop unit, making it possible to test all parameters and recipes in small scale before putting the production unit.

Figure 1

General Session 4 – Keynote Paper

44 MICROCAPSULES WITH CONTROLLED AND REMOTE RELEASE H. Möhwald, A.G. Skirtach, D. Volodkin, D.G. Shchukin; Max-Planck-Institute for Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam-Golm, Germany; [email protected]

Electrostatic, hydrogen bonding and hydrophobic forces have been used to form polyelectrolyte multilayers and capsules with well-defined wall, diameter, and composition of polymeric, biological, and inorganic molecules or particles. These weak interactions can be manipulated to control properties, in special permeability and adhesion. They exhibit glass transitions between room temperature and 90 C, depending on composition, pH, and salt. At high temperature, the permeability is drastically increased which may be used for environmentally dependent release. Inserting metallic nanoparticles as strong IR absorbers also remote and local release control is achieved via IR irradiation. This may be used for intracellular drug administration as well as for self-repairing coatings. These capsules as well as liposomes can be incorporated into surface coatings to obtain functional films. Two of their application perspectives will be described: (1) Encapsulating anticorrosion agents these will be released upon local

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potential changes accompanying a defect. The latter will thus be annealed and we have thus constructed a self-repairing coating; (2) Encapsulating a drug and releasing it triggered by light may influence cells attached to the surface. General Session 4 – Invited Paper

45 LIPID NANOPARTICLES FOR THE DELIVERY OF ACTIVES IN PHARMA, COSMETICS & CONSUMER CARE Cornelia M. Keck, Department of Pharmaceutics, Biopharmaceutics & NutriCosmetics, Free University Berlin, Kelchstr. 31, 12169 Berlin, Germany, [email protected]

Despite that solid nanoparticles can improve the delivery of actives, there are no therapeutic pharma products on the market (e.g. polymeric nanoparticles), the use in cosmetics is limited. Reasons are e.g. lack of accepted status of excipients and of large scale production methods. In contrast, lipid nanoparticles are made from toxicologically accepted surfactants and lipids, large scale production is possible by high pressure homogenization. The lipid nanoparticles followed the way of the success of the liposomes, which were first introduced to the cosmetic market (Dior, 1986) and later to pharma (first products around 1990). The first cosmetic products with lipid nanoparticles appeared on the market in 2005 (Dr. Rimpler), and now almost 40 products exist worldwide (e.g. La Prairie). Due to the solid character of the particle matrix, the lipid nanoparticles are more stable than liposomes, protect incorporated actives against degradation and can modulate their release. Oral bioavailability enhancement was shown for e.g. cyclosporine, fenofibrate and testosterone undecanoate. Lipids are known to promote the absorption of many drugs which is exploited in the lipid nanoparticles. The first pharma development will go into clinical phase I in 2010. General Session 4 – Invited Paper

46 ONE PROCESSING TECHNOLOGY – VARIABLE APPLICATIONS Gülden Yılmaz, Biobased products Bussiness Unit, Agrotechnology and Food Innovations B.V., Wageningen UR, Bornsesteeg 59 6708PD Wageningen, The Netherlands. [email protected]

Especially during the past decades controlled release technology has received a considerable attention for high volume applications. As a result, for these types of applications, most efforts are presently focused on continuous processing technologies and abundant matrix materials such as extrusion technology. By applying extrusion technology, encapsulation can be (cost) effectively and efficiently accomplished, with tailored release properties, such as extrusion technology. Furthermore this technology also provides the possibility to modify the formulation while performing encapsulation via enzymatic or chemical routes. A wide range of products are made available in the form of gels, coatable liquids, large range of particle sizes and forms as well as different release profiles and patterns are produced utilizing extrusion. The flexibility in utilizing extrusion technology has not only made the high volume applications available in an economically feasible manner but also opened new application fields for a wide range of encapsulants in the areas of cosmetics, personal

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care, household products, laundry applications, food, agriculture, pharmacy, biomaterials, textile, packaging, specialty papers and polymer processing. To conclude, encapsulation and controlled release of a wide range of compounds (solid, liquid, volatile, heat and/or oxidation sensitive) can be achieved in an efficient and cost- effective manner utilizing the extrusion technology. This is probably one of the main reasons for the emerging acceptance of this technology in numerous application areas of controlled release. Furthermore, the modification of the formulation characteristics can easily be done by means of small modifications to the processing technology and the components in the formulation. General Session 4 – Invited Paper

47 PARTICLE ENGINEERING TO DESIGN PROTECTION AND RELEASE OF MICROENCAPSULATED BIO-ACTIVES Jean Antoine Meiners; MCC Micro Capsule Concepts sa, Avenue de la Gare 6a, 2013 Colombier, Switzerland; [email protected]

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The purposes to perform micro encapsulation of bio-actives may be of different natures, but they have a common denomination i.e. delivery and release at the targeted place. A vast majority of these micro encapsulates require protection against moisture: moisture in the processing phase, moisture during shelf life or protection against body fluids. The protection may be for a short or prolonged period and moisture may be accompanied by heat treatment. Drying methods will have great importance for the particle shape and size. Spray drying will generate fine particles; freeze drying will result in flake shape with a large particle size distribution. Fluid bed drying and Zeolite drying may give particles a more spherical shape, which allows for increased micro encapsulation efficiency. Particle characterisation can be described by particle size, shape, internal structure and surface properties. All these elements play an important role for the quality of the micro encapsulation. Wall thickness may play a decisive role in efficient protection. Wall thickness should be equal at all places surrounding the core substance. Insufficient thickness could lead to premature leakage; too much coating may affect the release properties in situ. Total surface area to cover equally the core particle will be the primary characteristic to observe. Health and regulatory limitations for the use of certain polymers will cause restrictions in the choice of technology used for the micro encapsulation process. This document covers a composite particles approach, geared to the engineering of a particle with optimal physical properties for micro encapsulation purposes. Resulting capsules will be in the micro size range. Example particle structures:

Coating thickness as a function of particle surface area: 40 % coating

General Session 4 – Invited Paper

48 ENCAPSULATION WITH ALGINATES Berit L. Strand, Gudmund Skjåk-Bræk. Department of Biotechnology, Norwegian University of Science and Technology, Trondheim, Norway. [email protected]

Alginates are polysaccharides found in nature as structural component in marine brown

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algae and as capsular polysaccharide in some soil bacteria. Alginates are used as immobilization material for cells providing a mild encapsulation protocol by ionic cross linking at physiological conditions. The alginate gel capsule can serve as protection against the host immune system upon transplantation of therapeutic cells. This may allow treatment of different diseases, like diabetes mellitus, Parkinsons and brain tumors by cell transplantation without the use of immune suppressive drugs. Alginates are liner copolymers of 1-4 linked β-D-mannuronic acid (M) and α-L-guluronic acid (G). The physical properties of alginate gels correlate with alginate composition. Blocks of G strongly contribute to gel formation. However, recently, the role of alternating sequences in Ca-alginate gels has been elucidated. Enzymatic modification of alginates allows tailoring of composition and capsule properties. The lecture will focus on the use of alginate as encapsulation material for cells, in particular pancreatic islets for the treatment of diabetes. Important capsule properties such as stability, permeability and biocompatibility and the dependence on alginate and capsule composition will be covered. Poster Session 2- Contributed Paper

49 PEPTIDE-MEDIATED DELIVERY OF OPTICAL NANOSENSORS INTO S. CEREVISIAE Lise Junker Nielsen, Veli Cengiz Ozalp and Lars Folke Olsen, Department of Biochemisty and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark; [email protected]

In the study of the cell metabolism, knowledge of the concentration profiles of metabolites in time and space is key to understanding the dynamics of metabolic activities in the cell. Optical nanosenors present an interesting tool in this regard, as optical nanosensors allow real-time monitoring of small metabolites in living cells. In order for the optical nanosensor to be truly effective, a mode of intracellular delivery is needed, which ensures maximum loading of the nanosensors with minimum cell pertubation. Several techniques have been employed for nanosensor delivery, including gene gun delivery, electroporation, liposomal transfection and recently peptide-mediated delivery. Here we present a novel mode of delivery of a pH nanosensor into S. Cerevisiae utilizing the cell penetrating nature of cell-penetrating peptides (CPP's). The pH nanosensor is based on a pH sensitive fluorescent dye incorporated into a polyacrylamide nanoparticle, which was functionalized with two different CPP's known to mediate intracellular delivery of GFP or fluorophores into S. Cerevisiae. Of these two CPP's the artificial MAP peptide showed the best results in mediating intracellular delivery of the nanosensor, as determined by fluorescence spectroscopy. The localization of the nanosensors within the yeast cells was determined by confocal microscopy, and the intracellular pH of the yeast was measured and compared to results using other intracellular pH probes. The use of the MAP-peptide to mediate intracellular delivery can be readily extended to other polyacrylamide-based nanosensors, and possibly also nanosensors based on other nanoparticle formulations.

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Poster Session 2- Contributed Paper

50 DEVELOPMENT OF NANOPARTICLES CONTAINING PHOTOSENSITIZER WITH DIBLOCK COPOLYMER FOR PHOTODYNAMIC THERAPY Tsutomu Ono*, Ken Hirota*, Taro Shiraishi**, Ken-ichi Ogawara**, Kazutaka Higaki**, and Isao Sakata†, *Division of Sustainability of Resources, Graduate School of Environmental Science, Okayama University; **Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University; †Green Gold BioSystem Inc., 3-1-1 Tsushima-naka, Okayama 700-8350, Japan; [email protected]

Photodynamic therapy (PDT) requires the efficient delivery of photosensitizers to the tumor neighbourhood. General features of tumors include leaky blood vessels and ineffective lymphatic drainage. Therefore, nanocarriers containing hydrophobic photosensitizers access and accumulate in the tumors though the enhanced permeability and retention (EPR) effect. In this article, we developed biocompartible nanoparticles containing water-insoluble porphyrin derivatives by a solvent diffusion method using diblock copolymer. It is known that the nanoparticles with diameters <150 nm are more useful for EPR effect. By the combination of water- and oil-soluble poly(ethyleneglycol)- poly(lactic acid) (PEG-PLA) copolymers, PEG-coated PLA nanospheres with less than 100 nm in diameter were obtained. Furthermore, hydrophobic porphyrin was completely encapsulated in the particles. Singlet oxygen was released from the porphyrin-encapsulating nanoparticles by light irradiation, whereas porphyrin embedded in PEG-PLA nanoparticles did not diffuse in water. In addition, we found that colon-26 tumor cells were killed by visible light irradiation in vitro in the presence of 50 nM porphyrin embedded in PEG-PLA nanoparticles. Since this nanoparticle was easily prepared with only nontoxic copolymer and drug, it would be a promising nanocarrier for PDT. Poster Session 2 – Contributed Paper

51 APTAMER EMBEDDED POLYACRYLAMIDE NANOPARTICLES USED AS NANOSENSORS FOR METABOLITE DETECTION IN VIVO Veli Cengiz Ozalp, Lise Junker Nielsen and Lars Folke Olsen, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, Odense 5230, Denmark; [email protected];

Metabolite sensing is an important tool in understanding cell metabolism. Optical nanosensors are especially interesting since they allow real-time monitoring of metabolite concentrations to facilitate our understanding of the dynamics of cell metabolic activities. We developed an optical sensor based on aptamer recognition confined in polyacrylamide nanoparticles to measure adenosine nucleotide content inside cells. Aptamers are biorecognition elements selected through an evolutionary procedure from a combinatorial nucleic acid library. There has been numereous applications in sensor field based on aptamers since the invention of the selection method. The main attraction of aptamers as biorecognition units comes from artificial selection procedure allowing to obtain an aptamer for any desired target. In vivo applications of aptamers reported in the literature include targeting specific proteins in subcellular compartments for therapeutic

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and research purposes and controling specific gene transcriptions. The susceptibility of nucleic acids to nucleases and structural instability in cell environments are two major problems encountered in such studies. Modification of nucleic acids to make them nuclease resistant (2’-protected nucleotides like 2′-fluoro,2′-O-methyl, locked nucleic acids; phosphothiate linkages) is the major approach to overcome limitations imposed by enzymatic susceptibility, but also complicates the selection procedure. Nanoparticles confinement of aptamers can be an excellent alternative to prevent enzymatic degedation of aptamers inside cells during metabolite measurements. A pH nanosensor based on fluorescent dyes and a phosphate nanosensor based on fluorescent protein sensor have already been sucessfuly used for in vivo measurements showing that acrylmide particles at nanometer scales allow rapid diffusion of small molecules into nanoparticles indicating applicability of such designs. A fluorescent ATP switch probe based on an earlier selected DNA aptamer was embedded in polyacrylamide nanoparticles with diameter of 28 to 35 nm. The aptamer nanoparticle sensor was characterized for specific detection of adenosine nucleotides in buffer solutions. The reponse of the aptamer switch probe embedded in acrylamide nanoparticles was similar to the response of the free aptamer in solution. The enzymatic stability of nanoparticle-confined aptamers were tested by activity experiments in the presence of DNase. Finally, synthesized aptamer nanosensors were electroporated into yeast cells and the total concentration of adenosine nucleotide was determined in live cells. Aptamer-based polyacrylamide nanosensors as shown here can be readily extended to monitor any low molecular weight compound inside live cells by selecting new aptamers, converting them into fluorescent switch probes and embedding them in polyacrylamide nanoparticles. Poster Session 2 – Contributed Paper

52 ENCAPSULATION OF GOLD NANOPARTICLES IN A PNIPAM MICROGEL: NANOREACTORS AND MOLECULAR TRAPS FOR SERS R. Contreras-Cáceres1, S. Carregal-Romero, R. Álvarez-Puebla2, I. Pastoriza-Santos2, J. Pérez-Juste2, J. Pacifico2, L. M. Liz-Marzán;2(1)Depto. de Física Aplicada, Univer. de Almería, Ctra. Sacramento, 04120, Almería, Spain, (2) Dpto. de Química Física- Unidad Asociada CSIC-U. Vigo, 36310, Vigo, Spain; [email protected]

Nanocomposite materials consisting of a colloidal metal nanoparticle within a synthetic polymer hydrogel shell have attracted great attention due to potential applications in several fields such as catalysis, photonics, electronics, optics and biomedicine. Within the polymeric nanoparticles the field concerning stimuli-responsive nanomaterials has been investigated intensively in the past years. Among then one of the most commonly studied is the poly(N-isopropylacrylamide) (pNIPAM), that is, a thermoresponsive polymer that undergoes a phase transition from a hydrophilic, water-swollen state to hydrophobic, globular state when heated above its lower critical solution temperature (LCST) which is about 31-32ºC in water. In this work we are proposing an easy two-step procedure to pNIPAM encapsulate cetyltrimethyl ammonium bromide (CTAB) stabilized metal nanoparticlesn; the first step consisting of a CTAB promoted polystyrene coating of the metal nanoparticles in order to avoid aggregation and make them fully compatible with the precipitation

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polymerization of NIPAM in the second step. Figure 1 shows a representative TEM image of the Au-pNIPAM core-shell system. The study by UV-vis spectroscopy of the nanocomposites reveals that they present thermoresponsive optical (see Figure 1). A closer look at the position of the surface plasmon band of the gold nanoparticles shows that as the microgel collapses the band red-shifts ca. 10nm. This effect should be interpreted as a consequence of a core-shell structure since an increase in the local refractive index of the gold nanoparticles. The thermoresponsive properties of the systems is expected to allow us to control the catalytic properties of metal nanoparticles, as well as to control the interparticle distance in order to obtained two dimensional arrays. Recently, we have shown its applicability as molecular traps for surface-enhanced, spectroscopic, ultra-sensitive analysis. Poster Session 2 – Contributed Paper

53 BIOFERROFLUIDS FROM MAGNETIC POLYMER NANOCOMPOSITES

A. Millán1, R. Piñol1, N.J.O. Silva1, L. Gabilondo1, G. Ibarz1, L. Mohamed1, V. Sorribas2, R. Villa-Bellosta2, M. Gutiérrez3, M.S. Romero3, J.A. Moreno3, F. Palacio1; 1Instituto de Ciencia de Materiales de Aragón, CSIC – University of Zaragoza, 50009 Zaragoza, Spain; [email protected]; 2Department of Toxicology, University of Zaragoza, 50009 Zaragoza, Spain; 3Department of Hematology, University of Zaragoza, 50009 Zaragoza, Spain.

In this contribution the preparation of highly stable and persistent dispersions of superparamagnetic maghemite nanoparticles in a biocompatible fluid is described. The interest of maghemite nanoparticles extends into many areas of science and technology. They are particularly attractive for biomedicine where they are used as contrast agent in magnetic resonance imaging, drug targeting, immunoassays, molecular biology, DNA purification, cell separation and purification and hyperthermia therapy. The magnetic properties of maghemite nanoparticles change with size, internal structural disorder, aggregation, and interparticle separation. Therefore, to establish structure/properties relations and then suitable applications, a preparation methodology where these factors can be varied independently while keeping a narrow size distribution is very necessary. A nanocomposite made of maghemite nanoparticles uniformly distributed in a polymeric matrix can be prepared as a previous step to the particles dispersion in a fluid. Although nanocomposites have been produced from a large variety of polymers they often show a wide nanoparticles size distribution and they do not permit the variation of particle size in a large range. Here, we describe a method for the preparation of maghemite polymer nanocomposites with an average particle size varying regularly from 1.5 to 16 nm. The method is based on the use of N-base polymers that can form coordination bonds with transition metal ions. Maghemite is produced by in situ hydrolysis of iron halogen salts within a poly(4-vinylpyridine) (P4VP) polymer. The iron oxide nanoparticles are isolated and uniformly distributed within the matrix. Size distribution was determined by XRD, TEM and SAXS. Particle sizes are well controlled with 15% of size dispersion, not far from that obtained in organic solvent methods. Maghemite crystalline phase purity has been established by X-ray diffraction, TEM and Fe Mössbauer spectroscopy. The

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nanocomposite is dissolved and the resulting nanoparticles are further coated with hydrophilic and biocompatible polyethilenglycol (PEG) to make them persistent in the blood stream. The encapsulated maghemite nanoparticles formed a colloidal suspension in phosphate buffer saline solution (PBS) at physiological pH=7.4 obtaining a biologically compatible ferrofluid. Size distribution of nanoparticles in the ferrofluid is determined by Dinamic Light Scattering (DLS). In vitro and in vivo toxicology results and in vitro hematology tests for the behaviour of the ferrofluid in blood are also presented. Poster Session 2 – Contributed Paper

54 SMECTIC POLYMER VESICLES Lin Jia1, Rafael Piñol1, Amin Cao2, Patrick Keller1, Xiangjun Xing3, Mark Bowick3,Daniel Lévy1, Min-Hui Li1. 1 Institut Curie, CNRS, Université Pierre et Marie Curie, Laboratoire Physico-Chimie Curie, UMR168, 26 rue d’Ulm, 75248 Paris CEDEX 05, France, [email protected]; 2 Laboratory for Polymer Materials, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China; 3 Physics Department, Syracuse University, Syracuse NY 13244-1130, USA

Polymer vesicles are stable and robust vesicles made of block copolymer amphiphiles. Recent progress in the chemical design of block copolymers opens up the exciting possibility of creating a wide variety of polymer vesicles with different fine structures, functionalities and geometries. Polymer vesicles not only constitute useful systems for drug delivery or micro/nano-reactors but also provide valuable models for exploring the physics of two-dimensional order in curved spaces. By choosing suitable liquid-crystalline polymers for one of the copolymer components one can create vesicles with additional order in the two-dimensional membrane itself. Here we report ellipsoidal smectic polymer vesicles and faceted smectic polymer vesicles, formed from amphiphilic block copolymers in which the hydrophobic block is a smectic liquid crystal polymer. Smectic order on shapes of spherical topology inevitably possesses topological defects (disclinations). The competition between liquid crystal frank energy and membrane bending energy associated with the topological defects are responsible for the ellipsoidal shape and faceted shape observed in two kinds of polymer vesicles with smectic order in the membrane. These smectic polymer vesicles offer novel examples of the interplay between orientational/positional order and the curved geometry of a two-dimensional membrane. Poster Session 2 – Contributed Paper

55 HYBRID NANOSTRUCTURED MICROCAPSULES COMPOSED OF SILICA NANOPARTICLES AND LIPID EMULSIONS: ENCAPSULATION AND DELIVERY OF POORLY SOLUBLE DRUGS Angel Tan1,2, Spomenka Simovic1, Andrew Davey2, Thomas Rades3 and Clive A. Prestidge1; 1Ian Wark Research Institute, University of South Australia, 2Sansom Institute, University of South Australia, 3University of Otago, New Zealand; [email protected]

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We report on a new encapsulation and delivery vehicle for lipophilic molecules based on controlled assembly of sub-micron lipid emulsions and silica nanoparticles into dry microcapsules with an internal nano-porous structure (see Fig. 1). The specific internal matrix structure of the capsules (i.e. oil, emulsifier and drug embedded in a nanostructured silica matrix) facilitates increased drug loading compared with conventional lipid carriers, enhanced solid state stability, redisperability from the dry state, enhanced in vitro drug dissolution kinetics and improved orally dosed pharmacokinetics (in vivo studies in rat model) in comparison with positive control formulations and commercial products. Case studies are presented for poorly-water soluble, non-steroidal anti-inflammatory drugs (NSAIDs). The mechanisms of action for this nanostructured hybrid delivery system have been explored and are discussed. These hybrid lipid-silica (LipoceramicTM) microcapsules have wide ranging applications, e.g. as pharmaceutical, cosmetic and food products.

Figure 1. SEM images of hybrid lipid-silica (LipoceramicTM) microcapsules.

Poster Session 2 – Contributed Paper

56 DELIVERY OF MICROCONTAINERS WITH ACTIVE COMPONENTS TO CELLS Pilar Rivera Gil1, Bruno G. De Geest2 and Wolfgang J. Parak1 1 Biophotonic, Department of Physics, Philipps Universität Marburg, Germany; [email protected]; 2 Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Belgium

Polyelectrolyte capsules are made by layer-by-layer assembly of oppositely charged polyelectrolytes onto a template, which is at the end of the synthesis dissolved to obtain hollow capsules. These capsules can be filled with different bioactive molecules like drugs, antigens or genetic material for different purposes such as disease treatment, vaccination or gene delivery. For example, capsules filled with a pH-sensitive dye are taken up by cells and are able to deliver information about the local concentration of protons inside the cells. Using biological charged materials such as dextran and L-arginine, biocompatible and biodegradable hollow capsules are synthesized. By encapsulation of DQTM-Ovalbumine, a fluorogenic substrate for proteases the degradation of the capsules can be spectroscopically controlled. Furthermore, upon capsule

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biodegradation the encapsulated protein is available for enzymatic digestion. In this work, the intracellular processing of proteins mediated by biodegradable capsules is achieved.

Poster Session 2 – Contributed Paper

57 SYNTHESIS OF POLYURETHANE-UREA MICROCPASULES WITH PERFUME FOR TEXTILE APPLICATION Sofia N. Rodrigues, Isabel M. Martins, Filomena Barreiro, Vera Mata and Alírio E. Rodrigues, LSRE – Laboratory of Separation and Reaction Engineering, Department of Chemical Engineering, Faculty of Engineering of University of Porto, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal; [email protected]

This work is a contribution to the introduction of emergent technologies in the textile sector, namely the microencapsulation of fragrances and its application to obtain added-value products. Polyurethane/urea (PUU) microcapsules with a perfume have been produced using the interfacial polymerization technology for industrial application on textile substrate having in view man suits production. The majority of the available commercial microencapsulated fragrance systems for textile applications are based on formaldehyde systems (phenol-formaldehyde or melamine-formaldehyde resins), which are facing under the present environmental policies, several restrictions. In such context, the production of PUU microcapsules using the interfacial polymerization technology was performed as these systems appear as more attractive environmental friendly solution. Moreover, they are known as versatile polymer systems which can be tailor-made from a wide range of raw materials in order achieve the desired physical chemical and mechanical properties. The only drawback is that PUU systems must be designed and optimized taking into consideration the particularities of the active principle to be encapsulated. The extent of reaction of PUU microcapsules formation was followed by Fourier Transform Infrared Spectroscopy. Size distribution and morphology of the produced microcapsules were studied using particle size analysis, optical microscopy and scanning electron microscopy. The microcapsules mean size (based on volume distribution) of produced microcapsules is 10 µm and thickness around 1µm. Impregnation on textile substrates was tested both at laboratory level and at industrial scale. The fragrance release from textile substrates was measured with headspace chromatography. The content of microcapsules was released with light abrasion to simulate day-to-day wear, and fabrics impregnated at laboratory scale have survived to 9000 abrasion cycles. Microcapsules have continued to release aroma up to 5 dry cleaning washing cycles. The encapsulation efficiency and the presence of perfume on textile substrate were quantified through GC-FID-Headspace analysis. The encapsulation efficiency accounts for 55% of the loaded perfume used in the encapsulation process. Comparing each component of the perfume with their odor threshold the results showed that musk and limonene scent odor values are the highest so these are the components that we smell more. The amount of limonene component in the fabric was compared with its threshold and the odor value was calculated confirming that there is a decrease on odor value with 5 dry cleaning cycles.

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Poster Session 2 – Contributed Paper

58 CONTROLLED RELEASE STUDIES OF DEXAMETHASONE FROM NANOMETRIC HYDROGELS FOR OPHTHALMIC APPLICATIONS Virginia Sáez-Martínez, Nerea Argarate, Nerea Garagorri; Inasmet-Tecnalia, CIBER of Bioengineering, Biomaterials and Nanomedicine, Paseo Mikeletegui 2, 20011, Donostia-San Sebastian, Spain; [email protected]

Surgery and material implantation involve inflammation processes. For this reason it is important to deliver an antiinflammatory drug locally and over an extended period of time. On the other side, most antiinflamatory drugs have limitations in clinical administration due to their poor solubility and other unfavourable properties. The goal of this work is to develop an easy technique to manufacture nanometric polymeric hydrogels for clinical administration of antiinflamatory drugs with best efficacy and least side effects. These nanogels can show a very fast swelling-deswelling properties and can respond to changes in the surrounding conditions. Dexamethasone was chosen as a prototypical antiinflamatory drug. Nanogels of N-Isopropopylacrylamide-co-acrylic acid were prepared by precipitation polymerization in water. Several parameters were studied to improve the encapsulation efficiency of the nanogels and the quality of the in vitro drug release. Poster Session 2 – Contributed Paper

59 PHOTOPOLYMERIZATION OF FULLERENES ENCLOSED IN SWNT Yuika Saito, Mitsuhiro Honda, Prabhat Verma and Satoshi Kawata, Department of Applied Physics, Osaka University, 2-1 Yamadaoka, Suita, Osaka, Japan 565-0871; [email protected]

The photopolymerization of fullerene C60s encapsulated inside single-walled carbon nanotube (SWNT) is investigated in comparison with the non-encapsulated bulk C60. Through the observation of photopolymerization, we speculate the movement of C60s inside the SWNT, which is unique to the peapod structure. The polymerization conditions are monitored by the intensity of Ag(2) vibrational mode by Raman spectroscopy. The photopolymerization processes is accelerated under higher laser intensity in the case of bulk C60. On the other hand, encapsulated C60 have never been completely polymerized even under the threshold power that causes an ablation. However the spectral shape is broadened as the higher incident laser intensity is applied. By tracking the time dependence intensity ratio of monomer and polymer Raman peaks, C60 molecules and its origomers have a freedom to attach and detach with their neighbors assisted by the interaction with the SWNT walls. Because of this freedom of C60, the fabrication of a complete polymer chain inside SWNT is a vicious circle. Poster Session 2 – Contributed Paper

60 MELAMINE-FORMALDEHYDE MICROCAPSULES CONTAINING EUCALIPTUS ESSENTIAL OIL FOR FOOTWEAR APPLICATIONS

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M. M. Sánchez Navarro, F. Arán Aís, C. Orgilés Barceló, Footwear Research Institute INESCOP, Pol. Ind. Campo Alto 03600 Elda Alicante Spain, [email protected]

The situation of the industry today makes it necessary for new materials and concepts to be found, to be used as differentiating elements against competitors and to make products stronger in terms of quality, personal health and safety, or respect for the environment. In this sense, microencapsulation presents a new option for the shoe industry as its application can transform traditionally used materials or products into smart materials or products capable of interacting with feet. They can improve quality of life by incorporating therapeutic products for foot care such as properly dosed essential oils. The microencapsulation of active substances to be incorporated in different footwear components in order to obtain an "active shoe" presents an opening up of a new way of innovation. The eucalyptus essential oil is obtained from the leaves and the branches of the eucalyptus tree, 'Eucalyptus globulus'. The main active ingredient in eucalyptus oil is "eucalyptol" which has strong germicidal and disinfectant properties. Eucalyptus oil has an analgesic effect and is often used in preparations designed to relieve muscle, nerve and joint pains. Commonly, a mixture of the eucalyptus oil with almond oil is used in order to reduce the chance of irritation that the use of eucalytus oil alone could cause. Almond oil is a natural moisturizing agent very often used in the cosmetic industry due to its high essential oil content such as oleic and linoleic oils. Because it is not greasy, it is absorbed quickly. The polymerization in situ allows the formation of microcapsules containing water-immiscible dispersed phase, with improved mechanical properties and thermal stability. The properties of the membrane depend not only on its chemical structure but also on all the synthesis conditions. The polycondensation of the amino resin occurs in the continuous phase, and the phase separation is linked to the pH and the formaldehyde/melamine molar ratio. In this study a series of melamine-formaldehyde (MF) microcapsules containing a mixture of eucalyptus essential oil and almond oil was prepared by an in-situ polymerization (O/W) method to be applied to footwear materials (lining, insoles, etc…). The O/W emulsions were prepared by means of a Branson sonifier in order to obtain smaller sized droplets and therefore smaller MF microcapsules, near 1µm. In this study, the effect of the MF resin/ oil ratio and the influence on its structural and thermal properties of the resultant microcapsules were studied. The surface morphology and chemical structure of the microcapsules were investigated using an optical and scanning electron microscope (SEM), and Fourier-transform infrared analysis (FT-IR), respectively. The thermal properties of the samples were investigated by differential scanning calorimetry (DSC). The microcapsules size was measured using a Coulter size analyser. Poster Session 2 – Contributed Paper

61 SLOW RELEASE OF BIOCIDE FROM SILICA MICROPARTICLES IN WOOD PAINT Gitte Sørensen1, Søren Poulsen2, Holger Nissen3, Anne Louise Nielsen1 and Sune D. Nygaard1; 1Danish Technological Institute, Aarhus, 8000, Denmark; 2Dyrup A/S – R&D Wood Care, Søborg, 2860, Denmark; 3Velux A/S W-Research & Development – Materials, Østbirk, 8752, Denmark. [email protected]

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During the last decades more and more attention has been paid to the environmental effects of biocides which has resulted in more and stricter legislation on the use of biocides. To follow this movement the industry has to develop new and environmentally friendly ways to protect their products against microbial spoilage and the coatings industry is a part of this movement along with other industries. An important aspect of using biocides in coatings is the undesired high release of biocide to the environment. By changing the traditional way of adding biocide to wood paint this high biocide release can be minimized. Nowadays, biocide is dissolved in a small amount of organic solvent which is mixed into the wood paint. After application to wood this often leads to a burst release of biocide from the paint resulting in i) environmental contamination, and ii) disappearance of the biocidal effect sooner than desired. Furthermore, more biocide than needed is added to the wood paint. In order to avoid these problems microparticles of silica containing the biocide 3-iodoprop-2-ynyl N-butylcarbamate (IPBC) have been synthesized. By encapsulating IPBC the initial release of IPBC is slowed down, thereby minimizing release of biocide to the environment. Intelligent synthesis of the microparticles containing IPBC enables a controlled release profile for the biocide. The microparticles consist of a porous silica shell having a hydrophilic exterior which makes the particles readily dispersible in waterborne wood paints using no organic solvents. The hydrophobic core makes the particles able to encapsulate hydrophobic biocides such as IPBC. Microparticles containing IPBC are synthesized using sol-gel technology and are characterized using Focused-Ion-Beam Scanning Electron Microscopy (FIB-SEM) and other techniques. These investigations reveal that the particles are mainly found as spheres with diameters of 1-2 µm. Rudimentary release profile measurements of the particles were performed in test setups by suspending the particles in water and measuring the release of IPBC as a function of time using liquid chromatography-mass spectrometry (LC-MS). The results show how a proportion of 50 % of the IPBC is released to the water-phase within 24 hours whereas the rest remains encapsulated in the particles. To evaluate the effect of the microparticles in wood paints, several evaluation accelerated techniques are more appropriate to use, including QUV and inhibition zone assays. For this reason accelerated weathering tests have been performed in collaboration with the project partners, Velux A/S and Dyrup A/S. The effect of the biocide is evaluated by inhibition zone assays and the results are compared to those obtained using traditional wood paints containing non-encapsulated IPBC. These tests have shown positive effect of encapsulated IPBC after UV exposure. All in all it has been demonstrated that it is possible to encapsulate the important biocide IPBC in silica microparticles of roughly 1-2 µm in diameter. The microparticles containing IPBC have been shown to demonstrate controlled release of IPBC in model systems and a prolonged UV resistance of the biocide in subsequent accelerated weathering tests. Poster Session 2 – Contributed Paper

62 SILICA NANOPARTICLE AT AIR-WATER INTERFACES Stocco Antonio, Zang DY, Binks BP* and Langevin D, LPS, University Paris-Sud, 91405 Orsay, France; *Department of Chemistry, University of Hull, UK; [email protected]

Fumed Silica nanoparticles (Wacker Chemie, Germany) are extensively used in many industrial applications such as food and cosmetics. By changing the SiOH content, it is

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possible to tailor the surface activity of these particles. Emulsions and foams stabilized by these particles show extraordinary properties when compared to those stabilised by standard surfactants. Here, we present some results regarding the air-water interfacial properties and stabilization mechanisms in aqueous foams. At the water surface, we propose an ellipsometric model to evaluate the contact angle and the surface coverage of nanoparticles with different hydrophobic character. Moreover, surface tension measurements and Brewster angle microscopy were carried out in order to elucidate the absorption kinetics and the interfacial structure respectively. Foam dynamics was followed by a multiple light scattering technique. Detailed information on the bubble and particle arrengements were obtained by x-ray tomography. We can correlate the interfacial properties with foam aging showing that the underlying principle for foam stability depends on the surface tension γ and surface elasticity E through the Gibbs stability criterion E > γ/2 (for stable foam). Poster Session 2 – Contributed Paper

63 IN VITRO CELLULAR PHOTOTOXICITY OF NANOCAPSULES CONTAINING A METALLOPHTHALOCYANINE ON B16-F10 MELANOMA CELLS

Marigilson P. Siqueira-Moura1, Ana Paula F. Peti2, and Antonio C. Tedesco2*. 1Prog. P.G. em Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas-RP, Universidade de São Paulo, Ribeirão Preto-SP, Brasil; 2Depto. Química, Faculdade de Filosofia, Ciências e Letras-RP, Laboratório de Fotobiologia e Fotomedicina, Universidade de São Paulo, Ribeirão Preto-SP, Brasil*; [email protected]

The purpose of this work was to assess the photocytotoxic effect of Chloroaluminum Phthalocyanine (ClAlPc) encapsulated into nanocapsules (NC), and in its free form on mouse melanoma cells (B16-F10). NC were prepared according to interfacial polymer deposition after solvent displacement method. The phototoxicity assay was carried following 3 h cell incubation with free, and ClAlPc-NC at 0.50 µmol.l-1. In the phototoxicity studies cells were irradiated by a laser (wavelength 675 nm, output power 100 mW, fluence rate 14 mW.cm-2) at light doses of 20,100, and 500 mJ.cm-2. After 24 h, the cell viability was verified by standard MTT assay. For the evaluation of the chemical toxicity on B16-F10 cells in darkness conditions, were treated with ClAlPc (free and NC) at a concentrations of 0.50, 1.00, and 5.00 µmol.l-1. The concentrations of 0.50 and 1.00 µmol.l-1 did not show dark toxicity for both free ClAlPc and NC while at the highest concentration used it was observed a significant toxicity (p < 0.001). The lower concentration was chosen to be used throughout light toxicity assay. The phototoxic effect of free and encapsulated ClAlPc showed to be light dose dependent. The photodynamic damage was higher for irradiated cells with ClAlPc-NC than free drug (p < 0.05). Cellular viability decreases with the increase of light dose ranging from 84.3% (±8.64) to 21.6% (±1.30) for free ClAlPc, and from 62.0% (±5.69) to 8.4% (±0.82) for NC both at 20 and 500 mJ.cm-2, respectively. The treated cells with ClAlPc-NC at the highest light dose presented a cell survival fraction about 3-fold lower than that observed for free ClAlPc. This result could be explained by the better interaction between cells and nanocarrier leading to a higher accumulation of NC into target cells, as well as greater

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photocytotoxic effect due to reactive oxygen species generated. In summary, these findings indicate that ClAlPc-NC present an excellent phototoxicity on B16-F10 melanoma cells confirming potential of NC as drug delivery system applied to therapy against this kind of skin cancer, until now not treated by Photodynamic Therapy. Financial support: Grants from FAPESP 07/55319-0, 08/53719-4, 07/58809-9 (M.P.S.M.), and CNPq 101703/2008-2 (A.P.F.P.). Poster Session 2 – Contributed Paper

64 LAYERED DOUBLE HYDROXIDE NANOCRYSTALS LOADED WITH EXCHANGEABLE ANIONS FOR CONTROLLED CORROSION PROTECTION João Tedim1, Mikhail Zheludkevich1, Alena Kusnetzova1, Andrei Salak1 and Mário Ferreira1,2; 1University of Aveiro, CICECO, Dep. Ceramics and Glass Eng., 3810-193, Aveiro, Portugal; 2Technical University of Lisbon, IST, ICEMS, Av. Rovisco Pais 1049-001 Lisbon, Portugal; [email protected]

The quest for inert nanomaterials (nanoparticles, nanowires, nanosheets) able to provide controlled release of species is nowadays a hot-topic in pharmaceutical areas, with the so-called drug-delivery systems. Nevertheless, this concept is transversal to a large number of fields, including corrosion science. Following the banishment of carcinogenic chromium (VI) species, demands for “greener” technological solutions with the same (or superior) level of metal protection soon appeared. Different scientific and industrial groups are currently focused on the development of nanostructured systems capable to efficiently protect metals against corrosion by controlling the local release of inhibiting species where corrosion has started or is about to start. Here we report the synthesis and characterization of Layered Double Hydroxides (LDHs) with general formula [M2+

1-

xM3+x(OH)2]An-

x/n.mH2O. These systems are also called anionic clays and consist of stacks of positively charged, mixed metal hydroxides separated by galleries where anionic species and solvent molecules can be intercalated. The goal is to load these inorganic host structures with inorganic and/or organic corrosion inhibitors, so the LDHs will act as nanocontainers with two main roles: (i) release of corrosion inhibitor upon triggering conditions in the surroundings (e.g. pH changes, presence of aggressive species) and (ii) entrapment of detrimental anions to the metal substrates such as Cl- and SO4

2-. LDHs are prepared by anion-exchange and the resulting particles are analysed by X-ray diffraction and electron microscopies. Different parameters are investigated, including the effect of temperature and time of hydrothermal treatment on particle size and stability of aqueous suspensions. Subsequently, electrochemical techniques are used to assess the anticorrosion capabilities of these systems with respect to different metal alloys, namely hot dipped galvanised steel and aluminium 2024. As a result, LDHs loaded with corrosion inhibitors were found to impart corrosion protection upon metallic substrates in contact with NaCl aqueous solutions.

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Poster Session 2 – Contributed Paper

65 SELF-ASSEMBLY OF MULTI-STIMULI RESPONSIVE COPOLYMERS Klaus Tauer,1 Nancy Weber,1 and John Texter, 1,2, 1Max lanck Institute for Colloids and Interfaces, 14624 Golm (Potsdam), Germany; 2Schol f Engineering Technology, Eastern Michigan University, Ypsilanti, MI 48197 USA; [email protected] 

Ionic liquids (ILs; organic salts with melting points less than 100°C) and polymers of ionic liquid monomers (PIL) are exhibiting diverse uses in various types of chemical synthesis, electrochemical applications requiring high polarization, and alternative solvation while exhibiting high chemical and thermal stability and virtually no vapor pressure. The combination of such polymerized ILs with other monomers and materials

are providing diverse porous materials including polyelectrolyte membranes suitable for fuel cells and fast ion batteries, superstable latexes for new classes of organic coatings and composite films of nanocarbon, and diverse nanoparticle suspensions. The anion and solvent stimuli responsiveness of such IL-based materials provide chemical and physical switches around which new materials and processes may be designed. Core-shell reversible particle precipitation from aqueous di-stimuli-responsive diblocks composed of an ionic liquid (ILBr) block and an N-isopropyl acrylamide (NIPAM) block is demonstrated, whereby heat produces ultrastable particles with a polyNIPAM core and excess bromide produces stable particles with a polyILBr core, as is the sequential interconversion from the first cited core-shell combination to the other.

Poster Session 2 – Contributed Paper

66 HYBRID PLASMONIC COLLOIDAL NANOSTRUCTURES Benjamin Thierry, Ian Wark Research Institute, University of South Australia, Mawson Lakes, Australia, SA 5095; [email protected]

Plasmonic nanoparticles and nanorods, made of noble metals such as gold and silver, are arguably among the most promising nanomaterials due to their surface plasmon resonance (SPR) enhanced light scattering and adsorption. Gold nanorods are of particular interest as their plasmonic resonance can be easily tuned from the visible to the near-infrared (NIR) by changing their aspect ratio. The intrinsic optical properties of gold nanorods have been exploited to design various novel in vitro and in vivo diagnostic and therapeutic strategies based on light scattering, two-photon fluorescence, photoaccoustic

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effect, optical coherence tomography, and photothermal effect. A critical requirement towards their successful integration into functional nanodevices is the need for optimal surface functionalization procedures. Towards the design of a robust and universal gold nanorods functionalization procedure, we report here the use of an intermediate polymeric layer that acts as a steric stabilization agent during ligand exchange procedures. To demonstrate the versatility of this novel approach, gold nanorods have been functionalized with various ω-substituted alkanethiols such as 11-mercaptoundecaonic acid (MUA), 3-amino-5-mercapto-1,2,4-triazole, dodecanethiol and 3-mercaptopropyl-trimethoxysilane (MPTS). Partial functionalization at the gold nanorods ends with alkanethiol molecules such as MUA is usually observed due to preferential binding of thiols to the Au{111} surface due to the lower coverage of hexadecyltrimethylammonium bromide (CTAB). Taking advantage of the steric protection provided by a polyethyleneglycol layer, complete removal of the CTAB bilayer could be obtained in this work without impacting on the colloidal stability of the gold nanorods as shown by X-ray photoelectron spectroscopy, transmission electron microscopy and UV-vis measurements. The creation of well-defined functionalized interfaces enabled the manipulation, self-assembly and integration of the gold nanorods into complex multifunctional nanostructures. MPTS functionalization afforded vitreophilic nanorods that could be easily encapsulated within a silica shell and further loaded with fluorescent and Raman dyes. Hydrophobized nanorods displayed typical self-assembly features and have been integrated into hybrid plasmonic-micellar nanostructures that could be further loaded with chemotherapeutics such as paclitaxel and diagnostic agents such as indocyanine. In summary, the integration of gold nanorods into hybrid colloidal nanostructures is described towards the design of novel plasmonic diagnostic and therapeutic strategies. Poster Session 2 – Contributed Paper

67 MECHANICAL PROPERTIES OF SINGLE HOLLOW SILICA PARTICLES Doris Vollmer1, Lijuan Zhang1, Maria D’Acunzi1, Michael Kappl1, Günter K. Auernhammer1, Carlos van Kats2, Alfons van Blaaderen2; 1 Max Planck Institute for Polymer Research, Mainz, Germany; 2 Soft Condensed Matter, Debye Institute for Nanomaterials Science, Utrecht University, Utrecht, The Netherlands; [email protected]

Hollow particles of micron and sub-micron dimensions are abundant in nature in the form of bacterial or viral capsids. The shells’ mechanical properties determine their stability and flow behavior. We investigated the mechanical properties of single silica shells by force-distance spectroscopy. The spherical capsules of different diameters (800 nm and 1.9 µm) and shell thickness (15 nm thickness 70nm) were immobilized on a silicon substrate. Shells thinner than 15 nm could not be analyzed because they can be irreversibly deformed by capillary forces during drying. We probed the elastic response of the hollow particles by applying a point load, successively increasing the load until the shell broke. In agreement with the predictions of shell theory the deformation increases linearly with applied force for small deformations. For thicknesses larger than 20 nm the

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Young modulus is independent of shell thickness. However, it depends on the thermal history of the sample. It increases from 10 GPa for unheated shells to close to that of fused silica (80 GPa) after heating the hollow particles to 1100 °C. Heating transforms the large number of silanol groups into Si-Si bonds. This transformation leads to a compaction of the shells, which is reflected in a reduction of the diameter of the hollow particle as well as its shell thickness. Amazingly, tempering at 1100 °C induces smoothing of shells although the particles still remain spherical as shown by atomic-force-microscopy and scanning-electron-microscopy. Poster Session 2 – Contributed Paper

68 ENCAPSULATION AS A BUSINESS Dennis M. Vriezema, Lee Ayres, Dennis Lensen, Joost A. Opsteen, Tian Pu; Encapson BV, Toernooiveld 1, 6525 ED Nijmegen, the Netherland; [email protected]

The range of applications for the use of encapsulation is numerous. Much like the function of the cell membrane one can use encapsulation for protection, delivery, controlled release, compartmentalization, etc. At Encapson we focus on research and development of capsules for encapsulation in a broad range of applications. Besides encapsulation and capsule formation we also prepare the polymers that are used for encapsulation in-house. In this way we are able to tailor the properties of the resulting capsules exactly to the needs of the customer and application. We can tune for instance the (bio)degradation, release time, compatibility and permeability by varying the polymer type, molecular weight, ratio between blocks, building in of functional groups, etc. We are not limited to the use of only one method of encapsulation. We make use of internal phase separation, in-situ polymerization, layer-by-layer deposition and self assembly for e.g. the encapsulation of biomaterials, gases, catalysts and drugs, either hydrophobic or hydrophilic. When a client is thinking of applying encapsulation in their process or when they are interested in the benefits of encapsulation for new applications we can design and prepare capsules filled with the desired compound for testing.

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Poster Session 2 – Contributed Paper

69 DEVELOPMENT OF ACTIVATED SPHERICAL PARTICLES AS A SCAFFOLD FOR TISSUE REGENERATION Yanhong Wen, Lene Jørgensen, Eva Horn Møller and Hanne Mørck Nielsen, Dept. of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Science, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; [email protected]

Scaffolds are used in tissue engineering as a structural cell support and for the delivery of active substances for stimulation of cell growth. Natural as well as synthesized materials have been utilized to fabricate different types of scaffolds for these purposes. The aim of the present project is to develop optimized microspherical particles containing therapeutically active substances for combination with autologous stem cells intended for tissue regeneration. Variants of the polymer methoxy poly(ethylene glycol)-poly(lactide) copolymer) (MPEG-PLGA) has been chosen as the scaffold material for the preparation of microspheres. PLGA, which is approved by FDA as scaffold material due to its biocompatibility and biodegradability, is modified by MPEG to obtain a more hydrophilic and flexible surface. MPEG-PLGA microspheres were fabricated by the emulsion-solvent evaporation method using polyvinyl alcohol (PVA) as the surfactant. The microspheres were characterized with respect to external and internal morphology, porosity, particle size, degradation etc. The microspheres were prepared in varying sizes and porosities in order to optimize cell adhesion and loading/release properties. The residual water and surfactant polyvinyl alcohol (PVA) content were controllable by using freeze-drying. The active microspheres will be studies with cell systems of interest, in order to optimise the microparticle characteristics to achieve the desired cellular behaviour. Poster Session 2 – Contributed Paper

70 DEVELOPMENT OF AMORPHOUS DRUG NANOPARTICLES BY NovaSperse℠ TECHNOLOGY Deepak Thassu, PharmaNova Inc, Victor, NY, USA; Ren Xu, Beckman Coulter Inc., Miami, FL, USA; [email protected]

NovaSperse℠ is a proprietary platform technology developed by PharmaNova, Inc., to create amorphous nanoparticles of pharmaceuticals that are typically poorly water-soluble. NovaSperse℠ creates spherical nanoparticles of pure drug substances offering enhanced solubility and numerous advantages over nano-crystals and other type of nanoparticles. NovaSperse℠ technology is based on solvent displacement principles with precise control on formation of nuclei and molecular aggregates leading to desired particle sizes with a narrow particle size distribution that is characterized by photon correlation spectroscopy. The technology allows us to modify the nanoparticles surface properties which facilitates stabilization of nanoparticles and helps in developing smart nanoparticles for targeting purposes.

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The combined features of the NovaSperse℠ process and choices of stabilizers characterized by the surface zeta potential of nanoparticles result in stable suspensions of amorphous nanoparticles with good stability with small change in particle size during storage in various conditions. Poster Session 2 – Contributed Paper

71 SYNHTESIS AND CONTROLLED RELEASE FROM POLYMER MICROSPONGES, Aleš Zadražil and František Štěpánek, Department of Chemical Engineering, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague, Czech Republic; [email protected]

The aim of this work is to fabricate miniature sponge-like porous structures, which will be able to change their local properties (porosity, pore diameter) as a result of an external stimulus (pH, temperature, chemical composition of a solution). Thermo-responsive hydrogels based on a poly(N-isopropylacrylamide) are used for fabrication of micro-size spheres (in the size range of 10-100 µm). We use both liquid (acetone, ethanol) and solid (calcium carbonate) porogens for increasing, at various length-scales, the internal porosity of hydrogels during polymerization. The usage of porogens will lead to the creation of conducting channels and dead-end reservoirs, which may contain bulk liquid other than that contained in the expanded gel network. The expansion/contraction of the porous network will, consequently, cause reversible ejection/suction of the liquid from/to the reservoirs. In order to effectuate “remote control” of the polymer volume change, composite structures containing Fe2O3 nanoparticles are used. Upon the application of an external electromagnetic field, the particles can locally increase temperature and induce a transition from the expanded to the collapsed state of the polymer. The dynamics and extent of the polymer volume change as function of temperature was investigated by means of digital image analysis, and the microstructure of the porous network was visualized by SEM and x-ray microtomography. The kinetics of controlled release of model active substances from the micro-sponges has been investigated by time-dependent UV/VIS spectrophotometry. Applications of these active micro-sponges include targeted delivery or absorption of active ingredient in various complex environments of both biological and inorganic origin. General Session 5 – Invited Paper

72 FACILE AND CONVERGENT SYNTHESIS OF POLYMER-COATED GOLD NANOPARTICLE LIBRARIES

Matthew I. Gibson and Harm-Anton Klok*, Laboratoire des Polymères, Institut des Matériaux, Ecole Polytechnique Federale de Lausanne (EPFL), Station 12, Lausanne, CH-1015, Switzerland. [email protected]

In recent times the application of nanomaterials in biology and medicine has increased greatly. However, there is still a need for methods to synthesise well-defined nanoparticles of predictable size and surface functionality, in a readily accesible manner.

Chart I: Nanosuspension with narrow PSD N1Nanosuspension

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In this presentation, we present a new, two step strategy for the convergent synthesis of polymer-coated nanoparticle libraries, with precise control over the size and surface functionality of the particles. The first step involves the post-polymerization modification of a reactive polymer precursor to give a diverse polymer library from a small number of “master” templates. The polymers are synthesized in such a manner as to incorporate an orthogonal handle at one chain end, which can be used to, in a second step, tether the polymers onto preformed inorganic cores to give a brush-like surface coating. Starting from just 3 precursor polymers and 3 different sized particle cores, we synthesized a large, 75 member nanoparticle library, where the particle size is controlled by the inorganic core and the molecular weight of the polymer precursor and the functionality by the polymer coating. The library has also been used to evaluate the influence of particle structure on aggregation in various biologically relevant media. This facile method for nanoparticle synthesis will be useful to rapidly access model nanoparticles for structure-property relationships.

Scheme 1. Covergent synthesis of nanoparticle libraries via post-modification reactions. General Session 5 – Invited Paper

73 ASSEMBLY OF BIOINSPIRED, NANOENGINEERED MATERIALS FOR TARGETED DRUG DELIVERY

Angus P. R. Johnston, Lillian Lee, Christina Cortez and Frank Caruso, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Melbourne, Australia 3010; [email protected]

Targeted delivery of drugs to specific cells in the body has the potential to improve the treatment of many illnesses, including cancer and HIV. An emerging technique to deliver drugs is by immobilising the drug inside a nanocapsule, whereby the body is protected from potentially harmful side effects of the drug, while also preventing the drug from being degraded by the body. One way to prepare these capsules is by the layer-by-layer deposition of interacting polymers onto a sacrificial template particle. This technique allows for fine control over the properties of the capsule by altering the number of layers deposited, the material deposited at each layer, and also by controlling the assembly conditions. However, assembly of structures on the nanoscale requires fine control of the

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assembly process. DNA provides an ideal building block for such films, as it is biocompatible and the complementary base paring can be used to facilitate assembly of the film as well as induce structures into the film on a nanoscale. We show that stable, responsive DNA capsules can be synthesised and the properties of the film can be controlled using different DNA sequences. We also show that nanocapsules can be targeted specifically to colorectal cancer cells by modifying the surface of the capsule with an antibody. General Session 5 – Invited Paper

74 FORMATION OF SMART NANOCAPSULES FOR DEFINED SLOW OR SUDDEN RELEASE

Anna Musyanovych and Katharina Landfester; Max Planck Institute for Polymer Research, 55128 Mainz, Germany;

[email protected] A growing interest in the engineering of polymeric nanoparticles as specific carriers for drugs and imaging agents is generally focused on their tissue permeability. Especially an increased attention has gained to core-shell particles consisting of a liquid core owing to their utilization as sub-micrometer containers for the encapsulation of biologically active substances. The ideal nanocarrier will be one that is size and morphology specific, has the ability to encapsulate variety of compounds, could be functionalized with certain surface targeting ligands, and has the possibility to be delivered and to release the encapsulated material in a controlled way. Significant benefits of the miniemulsion technique offer formation of polymeric biocompatible/biodegradable capsules in the sub-micron size range with oil or aqueous core and different wall thickness. The main principle based on the formation of stable liquid-in-liquid immiscible miniemulsion droplets. The high stability of the droplets gives an opportunity to perform the reactions within the droplets or at their interface. Due to the lack of monomer diffusion processes throughout the polymerization, an efficient encapsulation can be obtained by phase separation inside the nanodroplets throughout the polymerization process, by nanoprecipitation of the polymer onto nanodroplets, or by an interfacial reaction at the nanodroplet’s interphase. As an example, biodegradable nanocapsules (size range 250 – 600 nm) with encapsulated dsDNA (790 base pairs) were produced via anionic polymerization of n-butylcyanoacrylate (BCA) carried out at the interface of homogeneously distributed aqueous droplets in the inverse miniemulsion. Fluorescent polyurea and crosslinked starch nanocapsules were synthesized by polyaddition reaction between the water-soluble diamine (or starch) and oil-soluble diisocyanate at the water-oil interface. Biodegradable poly(L-lactide), poly(ε-caprolactone), and poly(lactide-co-glycolide) particles have been obtained from the preformed polymer by combination of miniemulsion and solvent evaporation techniques, based on the precipitation of the polymer within the miniemulsion droplets and subsequent encapsulation of the hydrophobic material. Different triggers can be used for a slow or fast release of materials out of the nanocapsules.

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General Session 5 – Invited Paper

74 FORMATION OF SMART NANOCAPSULES FOR DEFINED SLOW OR SUDDEN RELEASE Anna Musyanovych and Katharina Landfester; Max Planck Institute for Polymer Research, 55128 Mainz, Germany; [email protected]

A growing interest in the engineering of polymeric nanoparticles as specific carriers for drugs and imaging agents is generally focused on their tissue permeability. Especially an increased attention has gained to core-shell particles consisting of a liquid core owing to their utilization as sub-micrometer containers for the encapsulation of biologically active substances. The ideal nanocarrier will be one that is size and morphology specific, has the ability to encapsulate variety of compounds, could be functionalized with certain surface targeting ligands, and has the possibility to be delivered and to release the encapsulated material in a controlled way. Significant benefits of the miniemulsion technique offer formation of polymeric biocompatible/biodegradable capsules in the sub-micron size range with oil or aqueous core and different wall thickness. The main principle based on the formation of stable liquid-in-liquid immiscible miniemulsion droplets. The high stability of the droplets gives an opportunity to perform the reactions within the droplets or at their interface. Due to the lack of monomer diffusion processes throughout the polymerization, an efficient encapsulation can be obtained by phase separation inside the nanodroplets throughout the polymerization process, by nanoprecipitation of the polymer onto nanodroplets, or by an interfacial reaction at the nanodroplet’s interphase. As an example, biodegradable nanocapsules (size range 250 – 600 nm) with encapsulated dsDNA (790 base pairs) were produced via anionic polymerization of n-butylcyanoacrylate (BCA) carried out at the interface of homogeneously distributed aqueous droplets in the inverse miniemulsion. Fluorescent polyurea and crosslinked starch nanocapsules were synthesized by polyaddition reaction between the water-soluble diamine (or starch) and oil-soluble diisocyanate at the water-oil interface. Biodegradable poly(L-lactide), poly(ε-caprolactone), and poly(lactide-co-glycolide) particles have been obtained from the preformed polymer by combination of miniemulsion and solvent evaporation techniques, based on the precipitation of the polymer within the miniemulsion droplets and subsequent encapsulation of the hydrophobic material. Different triggers can be used for a slow or fast release of materials out of the nanocapsules. General Session 5 – Invited Paper

75 ENGINEERING PARTICLES WITH BIOINTERFACES EMPLOYING VIRAL ARCHITECTURES Edwin Donath, Institute of Medical Physics & Biophysics, Leipzig University, Härtelstrasse 16/18, D-04107 Leipzig, Germany; [email protected]

Bringing together viruses and particles, is this just a curious idea, or is there more behind combining the properties of viral architectures with the benefits of artificial particles?

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The lecture will try to give an answer to this question, discusses the ways of how to couple viruses with particles, and outline the perspectives and areas of application. For many, viruses have a reputation of carrying and spreading infectious and dangerous agents. They consist of a protein coat that houses the genetic instructions for infecting and replicating itself in living cells. For the chemist or physicist however, viruses represent organic nanoparticles with interesting properties and functions. Viruses, which are assembled from proteins and nucleic acids into precise structures and topologies, can be engineered into attractive building blocks for various applications in novel nanocomposite materials. Their area of application ranges from technical devices to particle-based diagnostic assays and drug delivery. The co-localization of the viral genome representing the construction plan within the self-assembled viral particle offers enormous possibilities for molecular-biology-based engineering. If the genetic sequences encoding for the structural components of viruses are inserted into plasmids and expressed in cells it is possible to obtain virus-like particles that do not carry genetic material, and, thus, can be safely applied in materials and particle technologies. They can be produced employing culture cells as factories for mass-production. Attaching viruses onto particle surfaces requires proper techniques. Many viruses additionally carry a lipid envelope with proteins responsible for the entry of viruses into cells employing membrane fusion triggered by pH changes. Mimicking this natural infection pathway is one way of integrating viruses into the surface of lipid coated particles. The lipid layer has a dual function i) serving as the support for the viral elements, and ii) providing the particle surface with biocompatible properties. Engineering the capsid proteins of viruses with tags with a specific affinity for selected materials is another way of fabricating hybrid structures. In the lecture both ways will be illustrated with recent results from the work of author`s and from other groups. The outstanding performance of these structures will be demonstrated with recent examples, where virus-engineered particles and surfaces have been used in diagnostic assays. General Session 5 – Invited Paper

76 NANOCONTAINERS WITH CONTROLLED PERMEABILITY FOR FEEDBACK ACTIVE COATINGS Dmitry G. Shchukin, Department of Interfaces, Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, D14476 Golm, Germany; [email protected]

The new multifunctional coatings should combine passive components inherited from "classical" coatings and active components, which provide fast response of the coating properties to changes occurring either in the matrix of multifunctional coatings (e.g., cracks, local pH change) or in the local environment (temperature, humidity). Recent level of the surface science shows new opportunities for fabrication of active feedback coatings through the integration of nanoscale containers or continuous networks loaded with the inhibitor into coating matrix thus designing completely new coating of the "passive" host - "active" guest structure. The main idea here is to use nanocontainers with a shell possessing controlled permeability properties. As a result, nanocontainers are uniformly distributed in the passive matrix keeping active material in "trapped" state thus avoiding the undesirable interaction between active component and passive matrix and spontaneous leakage. When the local environment undergoes changes or if the active

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surface is affected by the outer impact, the nanocontainers respond to this signal and release encapsulated active material.The most important task is to develop nanocontainers with good compatibility with the matrix components, the possibility to encapsulate and upkeep active material and permeability properties of the shell controlled by external stimuli. The nanocontainers should also be of a size less than 300-400 nm; the nanocontainers of larger size can damage the integrity of the coating matrix forming large hollow cavities, which reduce the passive protective properties of the coating. Depending on the nature of the sensitive components (e.g., weak polyelectrolytes, metal nanoparticles) introduced into the container shell, reversible and irreversible changes of the shell permeability can be induced by various stimuli: changes of pH, ionic strength, temperature, ultrasonic treatment, alternating magnetic field, electromagnetic irradiation. Different responses can be then observed varying from fine effects like tunable permeability to more drastic ones like total rupture of the container shell. There are two mostly versatile approaches for preparation of the “intelligent” nanocontainers for feedback active coatings. A first one comprises layer-by-layer assembly of oppositely charged species on the outermost surface of the porous particles and nanotubes using polyelectrolytes, conductive polymers, biopolymers, and nanoparticles as constituents of the nanocontainer shell. Second approach involves the use of ultrasonic waves to fabricate inorganic and composite hollow nanospheres. In this case, a cavitation interface is employed as a reaction zone where a sensitive shell is formed from organic precursors or pre-formed nanoparticles adsorbed at the gas/liquid interface via polycondensation, polymerization, and particle melting (or sonoinduced welding). Ultrasonic synthesis can result in hollow spheres containing either water-immiscible or water-miscible liquid in their inner cavity. General Session 5 – Invited Paper

77 EMULSION BASED ENCAPSULATION Heidi Johnsen, Stephan Kubowicz, Per Stenstad, Lars Kilaas and Ruth Schmid. SINTEF Materials and Chemistry, NO-7465 Trondheim, Norway; [email protected]

Encapsulation in micro- and nanoparticles is an effective method for protection and controlled release of liquid and solid substances. There are numerous preparation methods available for producing particles and capsules. An important issue is the reliable and reproducible preparation by industrially scalable methods. The products and the processes must be technically feasible and affordable. The emulsion based method called “miniemulsion polymerisation” is an inexpensive process which is suitable for up-scaling to industrial production. Both liquids and solids can be encapsulated by miniemulsion polymerisation, provided that they do not interfere with the polymerisation process. The key feature of the miniemulsion process is the co-stabilizer added to the droplet phase before emulsification, as it stabilizes the system against Ostwald ripening. Miniemulsion polymerisation has been applied successfully for encapsulation of active compounds for agricultural products, cosmetics, personal care and household products, as well as in biomedical applications. Examples of encapsulated substances are liquid crystals, magnetic iron oxides, insect repellents and fragrances. Our current aim is to adapt the method for encapsulation of drugs and diagnostic markers in biocompatible and biodegradable polymers. The miniemulsion polymerisation technique has been applied to

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prepare nanoparticles of the biodegradable polymer poly(butyl-2-cyanoacrylate) (PBCA). For medical application as drug delivery system, characteristics of the nanoparticles surface are crucial to avoid clearance by the reticuloendothelial system. Therefore, to inhibit unspecific binding to cells in general, and to prevent an uptake by monocytes, nanoparticles having poly(ethylene glycol) chains at the surface have been synthesized. General Session 6

78 AMPHIPHILIC CORE-SHELL PARTICLES IN ADVANCED WASTEWATER TREATMENT TECHNOLOGY Pei Li,1 Chi Ho Fan,1,2 Jasper Choy,2 Ir Daniel M. Cheng2; 1 Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong; 2 Dunwell Enviro-Tech (Holdings) Ltd., 8 Wang Lee street Yuen Long Industrial Estate, Yuen Long, New territories. Hong Kong, P. R. China; [email protected]

Numerous scientific forecasters have predicted that shortage of clean water is going to be one of the biggest issues that humanity will have to face in the near- and medium-term future. China is in danger of being one of places hardest hit by problems that will inevitably come. Thus novel processes that can clean wastewater effectively are going to be in great demand. Through collaboration between the University and local industrial company, we have developed a new nanotechnology-based wastewater treatment system through combining novel amphiphilic core-shell particles and vibratory shear enhanced process (VSEP). The new polymer particles have functional hydrophilic shells and well-defined hydrophobic cores with particle sizes in nano- to submicro-scales. The unique core-shell design of the particles enables the shell to adsorb most of the organic and inorganic contaminants found in industrial wastewater and materials leached from landfills, while the core acts as a solid support for subsequent separation from the water. The nanoparticles, once saturated by contaminants, can be separated from the liquid by vibrating ultra-filtration systems. The recovered particles can be easily regenerated through simply changing the solution pH. Thus the re-activated particles can be used repeatedly without affecting their capacity to remove the targeted compounds. The regenerability of the core-shell nanoparticles is a new breakthrough which leads to a cost-effective zero discharge water treatment process. In addition, this novel wastewater treatment technology may replace the reverse osmosis (RO) technique because it is much simpler, more environmentally friendly process at a significantly lower operating cost. General Session 6

79 ENCAPSULATION APPROACHES IN ADVANCED DISPLAY TECHNOLOGY Simona Margutti, Fraunhofer IAO, Nobelstr. 12, 70569 Stuttgart, Germany, [email protected]

Electronic paper, also called e-paper, is a display technology designed to mimic the appearance of ordinary ink on paper. Unlike a conventional flat panel display, which uses a backlight to illuminate its pixels, electronic paper reflects light like ordinary paper and

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is capable of holding text and images, allowing the image to be changed later. The most representative examples of electronic paper are the technologies, introduced in the beginning of 2000, by the corporations E-INK and Gyricon. A common point of the developed technologies is the use of microencapsulated, electrically polarized particles. Examples of commercial electrophoretic displays include the high-resolution active matrix displays used in the Amazon Kindle, Sony Librie, Sony Reader, and iRex iLiad e-readers. These displays are constructed from an electrophoretic imaging film manufactured by E Ink Corporation. The main limitations of the E-INK and Gyricon approaches are the reduced application fields and the bichromality which could only overcome employing color filters. With the aim of getting over the intrinsic limitation of the today´s existing technologies, Fraunhofer Gesellschaft researchers in collaboration with the University of California Riverside (UCR) developed a technology based on microencapsulated colloidal photonic crystals. Characteristics of the encapsulated system are its memory effect and the not-required insertion in electronic circuit thus leading to broad applicability. The E-Ink and Gyricon systems will be described together with forthcoming technologies developed at Fraunhofer Gesellschaft and UCR. General Session 6

80 OPTICALLY ADDRESSABLE POLYMERIC MICROCAPSULES Matthieu F. Bédard§, Andre G. Skirtach# and Gleb Sukhorukov§; §SEMS University of London, Mile End, London, UK; Interfaces, 14424-Potsdam, Germany; [email protected]

The development of novel remotely addressable tools for encapsulation, storage and delivery of various materials at the micrometer scale is a particularly challenging topic of material science. Using microcapsules as a drug delivery agent for instance, not only requires the microcontainers to possess the sufficient mechanical stability or to be delivered at the correct target cells, but they should also possess an efficient remotely addressable release mechanism. Our aim is to develop polymeric microcontainers with highly efficient optically addressable release properties. Gold nanoparticles and photodynamic dyes were chosen to sensitize microcapsules for their spectral properties in the visible and near-IR as well as for their specific responses to laser irradiation. Microcapsules are constructed by the layer-by-layer procedure and light sensitive materials are incorporated in the capsules shell directly during the shell construction or as complexes with polyelectrolytes. The plasmonic band of gold nanoparticles is harvested to optically release encapsulated substances by inducing thermo-mechanical processes within the shell. Additionally, controlling the shape and distribution of gold nanoparticles can significantly increase the release performance of encapsulated materials by near-IR irradiation. Photodynamic dyes are catalysts with the ability to generate reactive oxygen species upon irradiation, offering an alternative to metal nanoparticles as an optical remote activation trigger. The question as to which enviromental parameters affect the ability of microcapsules to release encapsulated substances by optical means and the significance of these parameters in in vivo studies is also addressed.

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General Session 6 – Keynote Paper

81 INORGANIC ENCAPSULATION OF ORGANICS FOR IMAGING AND DELIVERY James H. Adair, Materials Research Institute, The Pennsylvania State University, University Park, PA 16802, USA, [email protected]

Calcium phosphate nanocomposite particles (CPNPs) are a broad-based nano-platform for both bioimaging and drug delivery. CPNPs are composed of fluorescence bioimaging molecules and/or drugs encapsulated within a calcium phosphate matrix. Typical mean diameter based on TEM particle counting is 20nm with a distribution range from 15 to 25nm. The CPNPs have been surface functionalized with a range of the agents including amine, citrate, polyethylene glycol (PEG), anti-CD71, holotransferrin, and penta- and deca-gastrin. The amine, citrate and PEG surface functionalized CPNPs have been used to deliver a variety of drugs to cancer cells in both in vitro and in vivo studies. The amine, citrate and PEG functionalized CPNPs are colloidally stable in a variety of physiological environments including phosphate saline buffer (PBS, 10mM phosphate buffered to pH 7.4 with 0.14M NaCl and 0.01m KCl) and a variety of cell culture media. We have demonstrated that the drug-laden CPNPs are capable of delivering anti-neoplastic drugs to various cells including human breast and melanoma cells of a highly hydrophobic experimental drug, ceramide. We have also shown that CPNPs undergo dissolution after endocytosis with subsequent release of the encapsulated contents into the cytosol (Muddana et.al, Nano Letters, 2008). Thus, the drug-laden CPNPs are an inherently stealthy strategy to deliver active agents to cells that are drug resistant as well as drug sensitive. Early detection is a crucial element for the timely diagnosis and successful treatment of all human cancers, but is limited by the sensitivity of current imaging methodologies. We have synthesized and studied bioresorbable calcium phosphate nanoparticles (CPNPs) in which molecules of the near-infrared (NIR) emitting fluorophore, indocyanine green (ICG), are embedded. The ICG-CPNPs demonstrate exceptional colloidal and optical characteristics. Suspensions consisting of 16 nm average diameter particles are colloidally stable in physiological solutions (phosphate buffered 0.15 M saline (PBS), pH 7.4) with carboxylate or polyethylene glycol (PEG) surface functionality. ICG doped CPNPs exhibit significantly greater intensity at the maximum emission wavelength relative to the free constituent fluorophore, consistent with the multiple molecules encapsulated per particle. The quantum efficiency per molecule of the ICG-CPNPs is 200 percent greater at 0.049 ± 0.003 over the free fluorophore in PBS. Photostability based on fluorescence half-life of encapsulated ICG in PBS is 500 percent longer under typical clinical imaging conditions relative to the free dye. PEGylated ICG-CPNPs accumulate in solid, 5 mm diameter xenograft breast adenocarcinoma tumors via enhanced retention and permeability (EPR) within 24 hours after systematic tail vein injection in a nude mouse model. See figure below. Ex situ tissue imaging further verifies the facility of the ICG-CPNPs for deep-tissue imaging with NIR signals detectable from depths up to 3 cm in porcine muscle tissue. Our ex vivo and in vivo experiments verify the promise of the NIR CPNPs for diagnostic imaging in the early detection of solid tumors. We have also shown that the PEG-ICG-CPNPs can be used to image pancreatic cancer with orthotopic tumors (i.e., surgically implanted in the mouse pancreas) in the nude mouse model.

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NIR images of fluorescence signals in ICG-CPNP mouse model (iii) and two controls. From Altinoglu et.al, ACS Nano, 2008. In addition to imaging, we have discovered that the PEG-ICG-CPNPs can be used for tumor growth arrest based on photodynamic therapy (PDT) using the ICG as the photosynthesizer. PDT is the treatment of diseased tissue with light in combination with an optically active compound known as a photosentisizer. Fickweiler et.al (J. Photochem. Photobiol. B-Biol., 1997) discovered that ICG was a photosentisizer for PDT in vitro for cancer cells However, conventional PDT with conventional photosentisizers suffers from undesirable side effects with systemic introduction into patients as well as lack of deep tissue penetration. Biological degradation of the free ICG in the bloodstream severely limits PDT to more topical, local treatment of cancer. However, Russin et.al (to be submitted) have recently shown that the PEG-ICG-CPNPs can be seen in the near infra-red to depths of at least 8cm. Furthermore encapsulation of the ICG in the CPNPs protects the ICG from biological degradation during in vivo transport to the cancer cells. The testing of the dye encapsulated nanoparticles on live mouse models was performed by a group led by pharmacologist Mark Kester at the Penn State Hershey College of Medicine. For xenografts of breast cancer in the nude mouse model, tumor growth is arrested by the PDT with 3 minutes of near infra-red radiation (l=785nm) at an intensity of 50J/cm2. In contrast, radiation treatment with 0.002J/cm2 only resulted in tumor growth arrest by 50 percent relative to controls. In preliminary data, we show similar effects with leukemia in the nude mouse model after PDT. Thus, photodynamic therapy combined with the nano-platform represented by the calcium phosphate nanocomposite particles has the potential to provide new and innovative opportunities in the identification and treatment of cancer.

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Speaker and Presenter Index (Alphabetically by Name with Abstract Number)

Adair, James; 81 Advincula, Rigoberto; 2 Akartuna, Ilke; 13 Altinoglu, Erhan; 14 Antequera-Garcia, Gema; 15 Arpagaus, Cordin; 16 Azevedo, Ricardo; 17 Bédard, Matthieu; 80 Brandau, Thorsten; 43 Burgess, Diane; 8 Choi, Won Sun; 18 Christensen, Andreas Lauge; 19 Christensen, Sune M.; 20 Dähne, Lars; 6 De Cock, Liesbeth; 21 De Geest, Bruno; 41 De Smedt, Stefaan; 5 Decher, Gero; 7 del Mercato, Loretta; 22 Dohnal, Jiri; 23 Donath, Edwin; 75 Doussineau, Tristan; 24 Erni, Philipp; 25 Fery, Andreas; 9 Giannachi, Chiara; 26 Hettrich, Kay; 27 Jantarat, Chutima; 28 Johnsen, Heidi; 77 Johnston, Angus; 73 Kamegawa, Katsumi; 29 Keck, Cornelia; 45 Klok, Harm-Anton; 72 Kokol, Vanja; 30 Kovacik, Pavel; 31 Küpcü, Seta; 32 Lee, Jonghwi; 33, 34 Lensen, Dennis; 35 Li, Pei; 78 Madarieta-Pardo, Iratxe; 36 Margutti, Simone; 79 Marison, Ian; 40 Martins, Isabel; 37 Meiners, Jean-Antoine; 47 Möhwald, Helmuth; 44

Musyanovych, Anna; 74 Mykhaylyk, Olga; 38 Nielsen, Lise Junker; 49 Ono, Tsutomu; 50 Ozalp, Veli Cengiz; 51 Poncelet, Denis; 1 Pastoriza-Santos, Isabel; 52 Piñot, Rafael Lacambra; 53, 54 Prestidge, Clive; 55 Quellet, Christian; 42 Rivera Gil, Pilar; 56 Rodrigues, Sofia; 57 Saez-Martinez, Virginia; 58 Saito, Yuika; 59 Sánchez Navarro, Magdalena; 60 Scheibel, Thomas; 10 Shchukin, Dmitry; 76 Sørensen, Gitte; 61 Stocco, Antonio; 62 Strand, Berit; 48 Sukhorukov, Gleb; 3 Tedesco, Antonio; 63 Tedim, João; 64 Texter, John; 65 Thierry, Benjamin; 66 van Herk, Alex; 11 Veršič, Ronald; 39 Vollmer, Doris; 67 Vriezema, Dennis; 68 Walther, Mathias; 4 Wen, Yanhong; 69 Xu, Ren; 12, 70 Yilmaz, Gulden; 46 Zadrazil, Ales; 71

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James Adair Penn State University 249A MRL Building University Park, PA 16803, USA [email protected] Rigoberto Advincula University of Houston Chemistry-136 Fleming Bldg 4800 Cullen Boulevard Houston, TX 77204, USA [email protected] Ilke Akartuna ETH Zurich Wolfgang-Pauli-Strasse 10, HCI G538 CH-8093 Zurich, Switzerland [email protected] Erhan Altinoglu Penn State University 221 Materials Research Lab University Park, PA 16802, USA [email protected] Gema Antequera-García Univerisdade de Vigo Grupo de Química Coliodal-Unidad Asociada CSIC 36310-Vigo, Spain [email protected] Francisca Arán Ais INESCOP, Spanish Footwear Research Institute Poligono Industrial Campo Alto Aptdo Correos 253 03600 Elda, Alicante, Spain [email protected] Cordin Arpagaus BÜCHI Labortechnik AG Meierseggstrasse 40 9230 Flawil, Switzerland [email protected]

Ricardo Bentes de Azevedo Universidade de Brasília Campus Darcy Ribeiro, Asa Norte Brasília, Distrito Federal, 70910-900, Brasil [email protected] Jennifa Baier Federal Institute for Materials Research and Testing(BAM) Unter den Eichen 44-46 12203, Berlin, Germany [email protected] Matthieu F. Bédard University of London Mile End Road London, E1 4SO, United Kingdom [email protected] Thorsten Brandau BRACE GmbH Taunusring 50 63755 Alzenau, Germany [email protected] Diane Burgess University of Connecticut 69 North Eagleville Storrs, CT 06269, USA [email protected] Bob Carr NanoSight Ltd Minton Park, London Road Amesbury, SP4 7RT, Wiltshire, United Kingdom [email protected] Lai Mei Chan PCTS Specialty Chemicals Pte Ltd 16 Joo Koon Crescent 629018 Singapore [email protected]

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Ping Kwong (Peter) Chan Nipsea Technologies Pte Ltd 16 Joo Koon Crescent 629018 Singapore [email protected] Michael Chavant Syngenta Breitenloh 5 4333 Münchwilen, Switzerland [email protected] Won San Choi Korea Basic Science Institute (KBSI) 664-14 Dukjin dong 1-ga Dukjin-gu, 561756, Jeonju, Republic of Korea [email protected] Tsu-Wei Chou University of Delaware 126 Spencer Lab Newark, DE 19716, USA [email protected] Andreas Lauge Christensen University of Copenhagen Nano-Science Center Universitetsparken 5 2100 Copenhagen East, Denmark [email protected] Sune M. Christensen University of Copenhagen Nano-Science Center Universitetsparken 5 2100 Copenhagen East, Denmark [email protected] Lars Dähne Surflay Nanotec GmbH Schwarzschildstrasse 8 12489 Berlin, Germany [email protected]

Liesbeth De Cock Ghent University Harelbekestraat 72 B-9000 Ghent, Belgium [email protected] Bruno De Geest Ghent University Harelbekestraat 72 B-9000 Ghent, Belgium [email protected] Stefaan De Smedt Ghent University Harelbekestraat 72 B-9000 Ghent, Belgium [email protected] Gero Decher University of Strasbourg CNRS Institut Charles Sadron CNRS Campus Cronenbourg 23, rue du Loess F-67034 Strasbourg, France [email protected] Loretta del Mercato University of Marburg Renthof 7 35037 Marburg, Germany [email protected] Chiara Dionigi CNR Bologna Institute for Nanostructured Materials Via P.Gobetti, 101 40133 Bologna, Italy [email protected] Jiri Dohnal Institute of Chemical Technology-Prague Technicka 5 16628 Prague, Czech Republic [email protected]

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Edwin Donath Institute of Medical Physics & Biophysics Leipzig University Härtelstrasse 16/18 D-04107 Leipzig, Germany [email protected] Louis Doorn Givaudan Huizerstraatweg 28 1411GP Naarden, The Netherlands [email protected] Tristan Doussineau Institute of Physical Chemistry Friedrich Schiller University of Jena Lessingstrasse 10 D-07743 Jena, Thuringia,, Germany [email protected] Ellie Dowell NanoSight Ltd Minton Park, London Road Amesbury, SP4 7RT, Wiltshire, United Kingdom [email protected] Adrian Downer International Paint Akzo Nobel Stoneygate Lane Felling Gateshead, NE10 0JY, Tyne and Wear, United Kingdom [email protected] Jing Dreher BASF SE GKP/D - J 550 67056 Ludwigshafen, Germany [email protected]

Philipp Erni Firmenich SA 7 Rue de la Bergère 1217 Meyrin 2, Geneva, Switzerland [email protected] Adolfo Fernandez-Valdes Centro de Investigación en Nanomateriales y Nanotecnología Parque Tecnológico de Asturias 33428 Llanera, Asturias, Spain [email protected] Andreas Fery Universität Bayreuth Universitätsstrasse 30 95444 Bayreuth, Germany [email protected] Blythe Fortier-McGill McGill University Otto Maass Bldg, Rm 447 801 Sherbrooke Ouest Montreal, H3A 2K6, Quebec, Canada [email protected] Nerea Garagorri-Gantxegi Health Unit, INASMET-Tecnalia Mikeletegi Paselaekua, 2 Tecnological Park 20009 San Sebastian (Guipuzcoa), Spain [email protected] Albert Geiger Roche Diagnostics GmbH Im Nonnenwald 2 / Bldg 242 82377 Penzberg, Germany [email protected] Chiara Giannachi Bracco Imaging SpA Via Egidio Folli 50 20134 Milano, Italy [email protected]

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Urs Gonzenbach ETH Zürich HCI G531 Wolfgang-Pauli-Strasse 10 8093 Zürich, Switzerland [email protected] Thomas Gottschalk BASF SE J550 – GKP/D Carl-Bosch-Strasse 38 67056 Ludwigshafen, Germany [email protected] Kay Hettrich Fraunhofer IAP Geiselbergstrasse 69 14476 Potsdam-Golm, Germany [email protected] Kiki Ikossi Defense Threat Reduction Agency 8725 John J. Kingman Road Fort Belvoir, VA 22060, USA [email protected] Chutima Jantarat Prince of Songkla University Pharmaceutical Chemistry Hatyai 90112, Songkla, Thailand [email protected] [email protected] Nuria Jimenez Alcon Cusi SA Camil Fabra, 58 08320 El Masnou, Barcelona, Spain [email protected] Heidi Johnsen SINTEF Materials & Chemistry Sem Saelands vei 2A 7465 Trondheim, Norway [email protected]

Angus Johnston The University of Melbourne Chemical and Biomolecular Engineering Parkville Melbourne, Victoria, 3010, Australia [email protected] Katsumi Kamegawa National Institute of Advanced Industrial Science & Technology 807-1 Shuku Tosu, Saga 841-0052, Japan [email protected] Cornelia Keck Free University Berlin Kelchstrasse 31 12169 Berlin, Germany [email protected] Harm-Anton Klok Ecole Polytechnique Fédérale de Lausanne STI-IMX-LP, MXD 112 1015 Lausanne, Switzerland [email protected] Dragutin Knezic Vertex Pharmaceuticals 130 Waverly Street Cambridge, MA 02139 ,USA [email protected] Tuomas Koiranen Fermion Oy Orion Group Ltd Koivu-Mankkaantle 6 A FI-02101 Espoo, Finland [email protected] Vanja Kokol University of Maribor Institute of Engineering Materials & Design Smetanova ul. 17 SI-2000 Maribor, Slovenia [email protected]

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Pavel Kovacik Institute of Chemical Technology-Prague Technicka 5 16628 Prague, Czech Republic [email protected] Seta Küpcü Universität für Bodenkultur Center for Nanobiotechnology Gregor Mendel Strasse 33 1180 Vienna, Austria [email protected] Klaus Last Follmann & Co Karlstrasse 59 32423 Minden, Germany [email protected] Jonghwi Lee Chung-Ang University 221 HeukSeok-Dong, DongJak-gu Seoul, 156-756, Korea [email protected] Dennis Lensen Radboud University Toernooiveld 1 6525 ED Nijmegen, The Netherlands [email protected] Pei Li (Pauline) Applied Biology & Chemical Technology Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong, P. R. China [email protected] Iratxe Madarieta-Pardo Health Unit, INASMET-Tecnalia Mikeletegi Paselaekua, 2 Tecnological Park 20009 San Sebastian (Guipuzcoa), Spain [email protected]

Nishil Malde Surface Measurement Systems 5 Wharfside, Rosemont Road London, HA0 4PE, United Kingdom [email protected] Andrew Malloy NanoSight Ltd Minton Park, London Road Amesbury, SP4 7RT, Wiltshire, United Kingdom [email protected] Simona Margutti Fraunhofer IAO Nobelstrasse 12 D-70569 Stuttgart, Germany [email protected] Ian Marison Dublin City University Glasnevin Dublin 9, Ireland [email protected] Melanie Martin Particles Conference 265 Clover Street Rochester, NY 14610, USA [email protected] Isabel Martins University of Porto Rua Dr. Roberto Frias s/n Edificio E, Piso 4, sala E413 4200-465 Porto, Portugal [email protected] Jean-Antoine Meiners Micro Capsule Concepts sa (MCC) Av de la Gare 6a 2013 Colombier, Switzerland [email protected]

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Helmuth Möhwald Max-Planck-Institute for Colloids & Interfaces Am Mühlenberg 1 14476 Potsdam-Golm, Germany [email protected] Rainer H. Müller Free University Berlin Department of Pharmacy Kelchstrasse 31 12169 Berlin, Germany [email protected] Anna Musyanovych Max Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz, Germany [email protected] Olga Myhaylyk Technische Universität München Klinikum rechts der Isar Institute of Experimental Oncology & Therapy Research Ismaninger Strasse 22 81675 Munich, Germany [email protected] Anne Louise Nielsen Danish Technological Institute Kongsvang Allé 29 8000 Aarhus, Denmark [email protected] Lise Junker Nielsen University of Southern Denmark Biochemistry and Molecular Biology Campusvej 55 5230 Odense, Denmark [email protected] Christine Oliver CSIRO-Food Science 671 Sneydes Road Melbourne, 3030, VIC, Australia [email protected]

Lars Folke Olsen University of Southern Denmark Biochemistry and Molecular Biology Campusvej 55 5230 Odense, Denmark [email protected] Tsutomu Ono Okayama University 3-1-1 Tsushima-naka Okayama 700-8530, Japan [email protected] Emilio Ortiz-Alba Centro de Investigación y Desarrollo Tecnológico Paseo de los tamarindos 400-B, Piso 3 Bosques de les Lomas Mexico, Distrito Federal 05120, Mexico [email protected] Veli Cengiz Ozalp University of Southern Denmark Biochemistry and Molecular Biology Campusvej 55 5230 Odense, Denmark [email protected] Isabel Pastoriza-Santos Departamento de Quimica Fisica, Unidad Asociada CSIC-Universidade de Vigo Lagoas-Marcosende Vigo, 36310, Spain [email protected] Rafael (Lacambra) Piñol Instituto de Ciencias de Materiales de Aragon Plaza de San Francisco s/n 50009 Zaragoza, Spain [email protected]

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Denis Poncelet ENITIAA Rue de la Géraudière, BP 82225 44322 Nantes, France [email protected] Clive Prestidge Ian Wark Research Institute University of South Australia Mawson Lakes Boulevard Adelaide, 5095, South Australia, Australia [email protected] Christian Quellet Givaudan Schweiz AG Ueberlandstrasse 138 CH-8600 Dubendorf, Switzerland [email protected] Pilar Rivera Gil University of Marburg Renthof 7 35037 Marburg, Germany [email protected] Sofia Rodrigues University of Porto Rua Dr. Roberto Frias s/n Edificio E, Piso 4, sala E413 4200-465 Porto, Portugal [email protected] Virginia Saez-Martinez Health Unit, INASMET-Tecnalia Mikeletegi Paselaekua, 2 Tecnological Park 20009 San Sebastian (Guipuzcoa), Spain [email protected] Yuika Saito Applied Physics Osaka University 2-1 Yamadaoka Suita, Osaka, 565-0871, Japan [email protected]

Magdalena Sánchez Navarro INESCOP, Spanish Footwear Research Institute Poligono Industrial Campo Alto Aptdo Correos 253 03600 Elda, Alicante, Spain [email protected] Thomas Scheibel Universität Bayreuth Universitätsstrasse 30 95440 Bayreuth, Germany [email protected] Dmitry Shchukin Max Planck Institute of Colloids & Interfaces Am Mühlenberg 1 14476 Golm, Germany [email protected] Gitte Sørensen Danish Technological Institute Kongsvang Allé 29 8000 Aarhus, Denmark [email protected] Roongnapa Srichana Prince of Songkla University Kanjanavanich Road Hatyai 90110, Songkla, Thailand [email protected] Antonio Stocco Universite Paris-Sud Laboratoire de Physique des Solides 91405 Orsay cedex, France [email protected] Berit Strand Norwegian University of Science & Technology Sem Saelandsvei 6/8 N-7491 Trondheim, Norway [email protected]

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Philip Sturzenegger ETH Zürich HCI G531 Wolfgang-Pauli-Strasse 10 8093 Zürich, Switzerland [email protected] Gleb Sukhorukov Queen Mary College University of London Mile End Road London, E1 4NS, United Kingdom [email protected] Honghao Sun Risø, Technical University of Denmark Micro & Nanotechnology 4000 Roskilde, Denmark [email protected] Antonio Tedesco Universidade de São Paulo Av. dos Bandeirantes, 3900, Vila Monte Alegre Campus USP-FFCLRP Ribeirão Preto, São Paulo, 14040-901, Brazil [email protected] João Tedim University of Aveiro CICECO, Ceramics and Glass Engineering Campus Universitário de Santiago 3810-193 Aveiro, Portugal [email protected] Elena Tervoort ETH Zurich Wolfgang-Pauli-Strasse 10, HCI G539 CH-8093 Zurich, Switzerland [email protected] John Texter Eastern Michigan University 430 W. Forest Avenue Ypsilanti, MI 48197, USA [email protected]

Benjamin Thierry Ian Wark Research Institute University of South Australia Mawson Lakes, SA, 5095, Australia [email protected] Judit Toth University of Pannonia Egyetem str 10 H8200 Veszprém, Hungary [email protected] Albert van Nierop Distrilab Particle Technology Olmenlaan 6C 3833 AV Leusden, The Netherlands [email protected] Alex M. van Herk Eindhoven University of Technology Polymer Chemistry Den Dolech 2 , PO Box 513 5600MB, Eindhoven, The Netherlands [email protected] Maria Eugenia Velazquez-Sanchez Parcar Desarrollos y Servicios SA de CV Centro de Investigación en Polímeros Blvd Manuel Avila Camacho No. 138 PH 1 y 2, Lomas de Chapultepec Deleg. Miguel Hidalgo, Distrito Federal 11710, Mexico [email protected] A.W.P. (Ronald) Vermeer Bayer Cropscience Alfred Nobelstrasse 50 40789 Monheim am Rhein,Germany [email protected] Ronald J. Veršič Ronald T. Dodge Co. 55 Westpark Road Dayton, Ohio 45459, USA [email protected]

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Doris Vollmer Max Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz, Germany [email protected] Dennis Vriezema Encapson BV Toernooiveld 1 6525 ED Nijmegen, The Netherlands [email protected] Mathias Walther Pfizer Group Ltd Ramsgate Road Sandwich, Kent, CT13 9NJ, United Kingdom [email protected] Weimin Wang Merck & Co, Inc 770 Sumneytown Pike, WP14-3 West Point, PA 19486, USA [email protected] Yanhong Wen Pharmaceutics and Analytical Chemistry Faculty of Pharmaceutical Science University of Copenhagen Universitetsparken 2 2100 Copenhagen, Denmark [email protected] Valérie Winckler-Desprez Roche Diagnostics GmbH Sandhofer Strasse 116 68305 Mannheim, Germany [email protected] Renliang Xu Beckman Coulter, Inc. 11800 SW 147 Avenue Miami, FL 33196, USA [email protected]

Gulden Yilmaz Wageningen UR Agrotechnology & Food Innovations BV Bornsesteeg 59 6708 PD Wageningen, The Netherlands [email protected] Ales Zadrazil Institute of Chemical Technology-Prague Technicka 5 16628 Prague, Czech Republic [email protected] Sulin Zhang Pennsylvania State University 212 EES Building University Park, PA 16802, USA [email protected] Vivian Mei-Sheng Lo Chou (Tsu-Wei Chou) Newark, Delaware, USA Zhanlan You (Honghao Sun) Roskilde, Denmark

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Receipt

This receipt acknowledges payment of _______________________ from __________________________________________________ by ____________________________________________________ for the conference registration fee for Particles 2009 held 11-14 July 2009 at the Holiday Inn Berlin – City West, Berlin, Germany. _______________________________________ On behalf of: Particles Conference 265 Clover Street Rochester, NY 14610-2246 USA EIN No. 16-1565388 Tel: 1-585-288-5913 Fax: 1-585-482-7795


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