Review Article Pharmaceutical Nanotechnology: Past, Present and Future M. Geetha 1 , K. N. Chidambara Murthy 2* , B.V. Basavaraj 3 and N. Ahalya 1 1 Department of Biotechnology, M. S. Ramaiah Institute of Technology, Bengaluru- 560 054, India, 2 Central Research Laboratory, M.S. Ramaiah Medical College and Hospital, Bengaluru- 560 054, India, and 3 Department of Pharmaceutics, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bengaluru-560 054, India. Received July 27, 2015; accepted September 21, 2015 ABSTRACT This article describes the historical perspective and emerging application of nanotechnology in pharmaceutical, agri-life and healthcare sectors. Nanotechnology is a multidisciplinary field that deals with fabrication and use of nanosized materials. Although nanotechnology is not a new concept, in the last few decades it has gained significant interest. There are several evidence to show that concept of nanotechnology was used since ancient times without regarding it as nano-materials, which included use of lead and lime based hair dye by ancient Egyptians, rampant use of ‘bhasma’ (Ashes of metals and natural drugs) in Ayurveda and so on. The nanomaterials possess unique physical and chemical characteristics, which are entirely different from their bulk materials and exhibits several biological benefits. These size-dependent properties of nanomaterials can be used to overcome some of the limitations encountered in medical arena. The application of nanotechnology is quite diverse and prominent streams like pharmaceuticals, healthcare, electronics, construction, environment, energy, information technology, biomimetics, agriculture, transport, and food processing and storage are tremendously benefiting from its advantages. This review provides a brief outlook on application of nanotechnology in the major thrust areas like, agriculture, environment and health. The compiled information will provide an insight on how the nanotechnology can be integrated between different areas of life sciences for better applications to human life. KEYWORDS: Nanotechnology; Nanomedicine; Agriculture; Environment; Health benefits. Introduction The term “nano” is derived from a Greek word meaning dwarf or extremely small. Nanotechnology is an interdisciplinary scientific approach that involves designing, development and application of materials & devices at molecular level in nanometer scale i.e., at least one dimension ranges in size from 1 to 100 nm, which is a one billionth of meter (Fakruddin et al., 2012). Although nanotechnology is considered as a modern science, the concept has history which dates back to 5 th century in Asia and 9 th century in Egypt. Gold and silver nanoparticles were employed by artisans of Mesopotamia to generate glittering effect to pots. With the development in science, nanotechnology has found to have wider range of applications in each and every aspects of life science (Fig. 1). This majorly includes pharmaceuticals, healthcare, electronics, construction, environment, energy, information technology, biomimetic, agriculture, transport, and food processing and storage etc. In India, nantotechnology was used in ancient system of medicine (Ayurveda) way back in 5000 BC, without the terminology “nano”. Some of the formulations and medicaments used in Ayurveda such as ‘bhasmas’ (it is ash of metal/herbs/natural materials rich in carbon, minerals and metal ions) (Pal et al., 2014) were made up of Nano sized materials. Similarly, Nano sized materials were also used in siddha, ancient system of medicine originated from south of India. Some of the well-known formulations used includes, Swarnabhasma, muktashukti-bhasma, tamra-bhasma, louhabhasma etc., used to treat muscular weakness, asthma, infertility etc., (Kulkarni, 2013). Fig. 1. Application of nanotechnology in different aspect of life science. International Journal of Pharmaceutical Sciences and Nanotechnology Volume 9 Issue 1January – February 2016 MS ID: IJPSN-7-27-15-CHIDAMBARA 3061
Transcript
Geetha et al: Pharmaceutical Nanotechnology: Past, Present and Future 3061
Review Article
Pharmaceutical Nanotechnology: Past, Present and Future M. Geetha1, K. N. Chidambara Murthy2*, B.V. Basavaraj3 and N. Ahalya1 1Department of Biotechnology, M. S. Ramaiah Institute of Technology, Bengaluru- 560 054, India, 2Central Research Laboratory, M.S. Ramaiah Medical College and Hospital, Bengaluru- 560 054, India, and 3Department of Pharmaceutics, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Bengaluru-560 054, India.
Received July 27, 2015; accepted September 21, 2015
ABSTRACT
This article describes the historical perspective and emerging application of nanotechnology in pharmaceutical, agri-life and healthcare sectors. Nanotechnology is a multidisciplinary field that deals with fabrication and use of nanosized materials. Although nanotechnology is not a new concept, in the last few decades it has gained significant interest. There are several evidence to show that concept of nanotechnology was used since ancient times without regarding it as nano-materials, which included use of lead and lime based hair dye by ancient Egyptians, rampant use of ‘bhasma’ (Ashes of metals and natural drugs) in Ayurveda and so on. The nanomaterials possess unique physical and chemical characteristics, which are entirely different from their bulk materials and exhibits several
biological benefits. These size-dependent properties of nanomaterials can be used to overcome some of the limitations encountered in medical arena. The application of nanotechnology is quite diverse and prominent streams like pharmaceuticals, healthcare, electronics, construction, environment, energy, information technology, biomimetics, agriculture, transport, and food processing and storage are tremendously benefiting from its advantages. This review provides a brief outlook on application of nanotechnology in the major thrust areas like, agriculture, environment and health. The compiled information will provide an insight on how the nanotechnology can be integrated between different areas of life sciences for better applications to human life.
KEYWORDS: Nanotechnology; Nanomedicine; Agriculture; Environment; Health benefits.
Introduction
The term “nano” is derived from a Greek word meaning dwarf or extremely small. Nanotechnology is an interdisciplinary scientific approach that involves designing, development and application of materials & devices at molecular level in nanometer scale i.e., at least one dimension ranges in size from 1 to 100 nm, which is a one billionth of meter (Fakruddin et al., 2012).
Although nanotechnology is considered as a modern science, the concept has history which dates back to 5th century in Asia and 9th century in Egypt. Gold and silver nanoparticles were employed by artisans of Mesopotamia to generate glittering effect to pots. With the development in science, nanotechnology has found to have wider range of applications in each and every aspects of life science (Fig. 1). This majorly includes pharmaceuticals, healthcare, electronics, construction, environment, energy, information technology, biomimetic, agriculture, transport, and food processing and storage etc.
In India, nantotechnology was used in ancient system of medicine (Ayurveda) way back in 5000 BC, without the terminology “nano”. Some of the formulations and medicaments used in Ayurveda such as ‘bhasmas’ (it is ash of metal/herbs/natural materials rich in carbon,
minerals and metal ions) (Pal et al., 2014) were made up of Nano sized materials. Similarly, Nano sized materials were also used in siddha, ancient system of medicine originated from south of India. Some of the well-known formulations used includes, Swarnabhasma, muktashukti-bhasma, tamra-bhasma, louhabhasma etc., used to treat muscular weakness, asthma, infertility etc., (Kulkarni, 2013).
Fig. 1. Application of nanotechnology in different aspect of life science.
International Journal of Pharmaceutical Sciences and Nanotechnology
Volume 9Issue 1January – February 2016
MS ID: IJPSN-7-27-15-CHIDAMBARA
3061
3062 Int J Pharm Sci Nanotech Vol 9; Issue 1 January February 2016
The central concept of nanotechnology was drafted over a longer period. It was introduced way back in 1959, by Richard Feynman, an American physicist who gave a talk on “There's Plenty of Room at the Bottom." He suggested the possibility to create nanosized products with the manipulation of atoms and molecules.
The term "nano-technology" was introduced into the scientific world by the Tokyo Science University Professor ‘Norio Taniguchi’ in 1974 to describe the precision manufacture of materials with nanometer tolerance.
Nanotechnology got revolutionized with the invention of Scanning Tunneling Microscope (STM) and Atomic Force Microscope (AFM), which enabled the imaging of individual atoms or molecules. In 1985, Harry Kroto, Richard Smalley, and Robert Curl team discovered fullerene C60, who won the Nobel Prize in chemistry. In 1986, Drexler published a book named “Engines of Creation: The Coming Era of Nanotechnology” to describe molecular nanotechnology.
In 1991, SaumioIijima discovered carbon nanotubes and by 2000, the United States government launched the National Nanotechnology Initiative (NNI – a Federal visionary research and development programme for nanotechnology-based investments through the coordination of 16 various US departments and independent agencies) and these paved way for the progress in research and development in the field of nanotechnology (Roco, 2004).
Synthesis of nanomaterials
Basically "Top down" and "Bottom up" are the two approaches employed for creating nano-materials.
In the top-down (physical) approach, the bulk materials are gradually broken down to nano-sized materials by machining and etching techniques. It deals with methods such as diffusion, thermal decomposition, arc discharge, irradiation, etc.
In contrast, the atoms or molecules are assembled into molecular structures in the nanometer range in the bottom-up approach, which is commonly applied for chemical and biological synthesis of nanoparticles (Lengke et al., 2011). The self-assembly lipid molecules into nano-structure such as liposomes can be considered as a classical example on the bottom-up approach for constructing nanomaterials (Abu-Salah, 1992). The advantage of bottom-up approach would be a nearly infinite flexibility to create any substance, object, device, machine or material through atom (or molecule) by atom (or molecule) construction (Abu-Salah et al., 2010) and is considered to be an ideal approach for nanotechnology (Mansoori, 2002).
Traditionally nanoparticles were produced only by physical and chemical methods. High-energy ball milling, melt mixing, physical vapor deposition, laser ablation, sputter deposition, colloidal route, sol-gel etc., are the major methods employed for nanomaterial synthesis.
Some of the methods include Sol-gel technique: It is a wet chemical technique,
where two types of materials or components,
namely sol and gel are used. This method is used for the fabrication of metal oxides from a chemical solution, which act as a precursor for integrated network (gel) of discrete particles or polymers. The precursor sol can either be deposited on the substrate to form a film, cast into a suitable container with desired shape or used to synthesize powders.
Solvothermal synthesis: It is a versatile low temperature route, in which polar solvents under pressure and at temperatures above their boiling points are used. Under solvothermal conditions, the solubility of reactants increases significantly, enabling reaction to take place at lower temperature.
Chemical reduction: It is the reduction of ionic salts in an appropriate medium in the presence of surfactant using reducing agents. Some of the commonly used reducing agents are sodium borohydride, hydrazine hydrate and sodium citrate.
Laser ablation: This is the process of removing material from a solid surface by irradiating with a laser beam. At low laser flux, the material is heated by absorbed laser energy and evaporates or sublimates. At higher flux, the material is converted to plasma. Depending upon materials optical properties and the laser wavelength the laser energy is absorbed and corresponding amount of material is removed. This method is employed in making carbon nanotubes.
Inert gas condensation: In this method, different metals are evaporated in separate crucibles inside an ultra-high vacuum chamber filled with helium or argon gas at typical pressure of few hundred Pascal. As a result of inter atomic collisions with gas atoms in chamber, the evaporated metal atoms lose their kinetic energy and condense in the form of small crystals which accumulate on liquid nitrogen filled cold, finger like gold nanoparticles are synthesized from gold wires (Rath et al., 2014).
Biosynthesis of nanoparticles
The synthesis of nanoparticles by physical and chemical processes is not economical due to high cost for processing and raw materials. Furthermore, chemicals reagents used normally for synthesis and stabilization, are toxic and some of them will produce toxic by/co-products. To overcome this limitation, researchers found the alternate route for nanoparticle synthesis using microorganisms and plant extracts. This will be a low cost and eco-friendly technique, which is also referred as green synthesis. Nature has devised various processes for the synthesis of nano and micro length scaled inorganic materials, which contributed to the development of relatively new and largely unexplored area of research based on the biosynthesis of nanomaterials (Mohanpuria et al., 2008).
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Reference
Renugadevi et a
Song et al., 2010Lu et al., 2012
Jain et al., 2009Bao et al., 2010
Ankamwar et alParida et al., 20Kuang et al., 201
Narayanan et al
). Hence, it of commodi
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3064 Int J Pharm Sci Nanotech Vol 9; Issue 1 January February 2016
toxic side effects. Christou et al., (1998) successfully generated transgenic plants with DNA-absorbed on gold particles. Even carbon nanotubes (CNTs) and metal oxides contribute in crop improvement. CNTs in tomato seeds increased germination efficiently due to enhanced water uptake ability (Khodakovskaya, 2009). As nano sensors are user friendly and facilitate proficient use of agricultural natural assets like water, nutrients and chemicals during farming. It makes use of nanomaterials and global positioning systems with satellite imaging of fields and might make farmers to detect crop pests or facts of stress such as drought. Nano-sensors disseminated in the field are able to sense the existence of plant viruses and the level of soil nutrients (Ingale et al., 2013). Integrated pest management demands quick on-site detection of pathogens. The portable diagnostic equipment, nanoparticle-based, bio-barcoded DNA sensor, and Quantum dots have potential applications in the detection of plant pathogens and toxigenic fungi. Nano based mobile diagnostic assays have been developed to rapidly detect plant disease and may be used to prevent epidemics. These diagnostic kits not only increase the speed of pathogen detection but also increase the precision of the diagnosis. Additionally, the combination of nanotechnology with microfluidic systems has been effectively applied in molecular plant pathology and can be adapted to detect specific pathogens and toxins (Khiyami, 2014).
It has also become necessary to reduce the accumulation of toxic pesticides, herbicides, and fertilizers in plants, which serve as food for both human and animals. Nano encapsulated fertilizers, pesticides, herbicides are eco-friendly with the minimal consumption and extended release time (DeRosa, 2010). Honeycomb-like layered crystal structure of Nano clays and zeolites filled with nitrogen, potassium, phosphorous, calcium and a complete set of minor and trace nutrients acts as a nutrients supply that are slowly released "on demand" (Chinnamuthu et al., 2009). The porous properties and capillary suction of zeolites also assist in water retention, thus increases crop production in areas prone to drought (Prasad et al., 2014). Nano-barcodes and nano-processing technique help to assure the quality of agriculture products. Li et al., (2005) used the idea of nano-barcodes that tag to multiple pathogens in the farm, which can be detected by simple fluorescent tools. In spite of using chemicals and radiations, carbon nanotubes and magnetic nanoparticles could be employed for efficient purification of irrigation water. Table 2 provides information on bioactive compounds that are utilized as fertilizers and nanocarrier systems.
Nanotechnology aids to recycle agricultural waste, which not only reduce the cost of agriculture, will also help to protect environment to the greater extent. Cellulose and fibers discarded as waste from cotton industry are developed as nanofibers, which are employed as fertilizers or pesticide absorbents. Rice husk can be used for the production of high quality nano-silica (Mishra et al., 2013). It has been reported that nano-silica triggers plant growth, promoting rhizobacteria and
increases its total soil population by maintaining the soil pH. Thus, nano-silica can be included in fertilizer formulations to enhance soil properties for better crop yield (Karunakaran et al., 2013).
TABLE 2
Bioactive compounds and nanocarrier systems.
Active compound Nanocarrier Encapsulation
efficiency Reference
Azadirachtin
Alginate coated with starch and PEG
80%
Jerobin et al., 2012
Azadirachtin
Poly (ε-caprolactone) (PCL)
98%
Forim et al., 2013
Carvacrol
Chitosan/Pentaso-diumtripoly-phosphate
14-31%
Keawchaoonet al., 2011
Curcumin Hydroxypropyl cellulose
67%
Bielska et al., 2013
Garlic essential oil
Polyethylene glycol (PEG)
80%
Yang et al., 2009
Rotenone Chitosan 70%
Lao et al., 2010
Protein beauvericin
Chitosan 85%
Bharani et al., 2014
Role of nanotechnology in protection of environment
In last two decades with increased urbanization and industrialization and our ignorance on environmental protection has made this planet less safe for human and other life. It has become necessary to save the environment to ensure present and future well-being, as it is the most important resource for life. Nanotechnology plays an important role in environment protection by contributing novel and cost effective means for monitoring and detection of pollution, along with remediation of pollutants (EPA, 2007) (Table 3). Nanotechnology enables to design cleaner industrial processes and eco-friendly products and plays a vital role in pollution control.
TABLE 3
Application of nanotechnology in environment protection.
Nanomaterials Applications References
Titanium dioxide based nanoparticles
Removal of different organic pollutants, nitrobenzene, phenol etc., can be used for the degradation of dyes.
Chen et al., 2003 Stathatos et al., 1999; Makarova et al., 2000
Iron based nanoparticles
ZVI can be used for the removal of arsenic, nitrate. Nanoscale metallic iron is very effective in destroying a wide variety of contaminants such as chlorinated methanes, ethenes, benzenes, brominated methanes, trihalomethanes, other polychlorinated hydrocarbons, pesticides and dyes.
Wang et al., 1997 Choe et al., 2000 Zhang, 2003
TABLE 3 Contd...
Geetha et al: Pharmaceutical Nanotechnology: Past, Present and Future 3065
Nanomaterials Applications References Gold nanoparticles Degradation of TCE and
halocarbon–based pesticides and oxidation of mercury, in detecting CO and NOx.
Norton, 2008 Thompson, 2007
Bimetallic nanoparticles
The main principle involved in case of bimetallic nanoparticles is reduction and adsorption. Pd/Fe and Cu/Fe are involved in dechlorination and denitrification respectively.
Liou et al., 2005 Wang et al., 2008
Nanoclays Fe-nanocomposite, ETAS (new class of nano-sized large porous titanium silicate), CTS/MMT (chitosan /Montmorillonite) nanocomposite can be used for the removal of heavy metals and organic pollutants.
Feng et al., 2003 Choi et al ., 2006 Wang et al., 2007
Carbon nanotubes Efficient sorbent for organic and inorganic contaminants, a disinfectant to control pathogens. CNT filters can be used to remove pathogenic microorganisms and particulates in waste water. Detect and monitor the concentration of toxic gases released such as NOx and SO2.
Tahaikt et al., 2007; Srivastava et al., 2004; Ueda et al., 2008; Suehiro et al., 2005
Magnetic nanoparticles
The potential magnetic nanoparticles for the removal of heavy metals and organic pollutants are magnetic alginate and chitosan nanoparticles, Polyacrylic acid-based iron oxide etc.
Chang et al., 2006 Chen et al., 2004
One of the major areas of application is concerned with air pollution. The technology offers nano-catalysts that work to speed up chemical reactions that transform harmful vapors from vehicles and industrial plants into harmless gases (Thakur et al., 2013). Nanofilteration membranes and nanosensors could be applied for trapping gas emissions. Gold nanoparticles (GNPs) and CNTs based nanosensors have the potential to detect toxic gases like, carbon monoxide (CO), nitrogen oxides (NOx) and sulfur dioxide (SO2) (Bhawana, 2011; Thompson, 2007; Ueda et al., 2008).
Nanotechnology eases the water cleaning process with hydrodehalogenation and reduction catalysts for the remediation of various organic and inorganic ground water contaminants (Nutt, 2005). The semiconducting property of Titanium dioxide (TiO2) plays an important role in the removal of different organic pollutants through excitation with light. These TiO2 based nanoparticles find its application in waste water
treatment as a photocatalyst and can be used for the degradation of dyes, removal of nitrobenzene, phenol etc. (Makarova et al., 2000). It has been investigated that gold in water purification device can degrade Trichloroethylene (TCE) and halocarbon–based pesticides and involve effective oxidation of mercury (Xiao et al., 2003; Norton, 2008).
Iron based nanoparticles can be injected to clean-up soil contaminated with heavy metals. Zero-valent iron (ZVI) can be used for the removal and sorption of arsenic, nitrate in contaminated soil (ZenuJha et al., 2011).
The technology also contributes to meet the energy demand. Single-walled nanotubes (SWNTs) and Multi-walled nanotubes (MWNTs) with their remarkable properties found application in photovoltaic devices, hydrogen fuel cells, biofuel cells. In capacitors utilization of CNTs as electrode material enhances its ability to store high energy (Ong et al., 2010). It has been reported that calcium and magnesium oxide nanoparticles have been used as catalysts in transesterification of oil to biodiesel (Bhupinder, 2014).
Application of Nanotechnology in Health
Nanotechnology finds major application in the field of medicine and health care, since nanomaterials possess novel properties such as large surface area, increased strength, specialized optical and electrical properties. Nanotechnology revolutionizes the conventional methods that are used extensively to detect and treat diseases. Advances in nanotechnology field proved to have potential benefits in all the area of health care such as prevention, diagnostics, treatment and prognosis. Fig. 3 shows the possible applications of nanotechnology in health care. The specific applications are in the area of drug development, targeted drug deliver, gene therapy, tissue regeneration etc. (Navalakhe et al., 2007). Health care applications may be broadly divided as diagnostics, treatment and others.
NANO
TECHNOLOGY
DRUG DISCOVERY
TISSUE REGENERATION
GENOMICS AND PROTEOMICS
DIAGNOSTICS
GENE THERAPY
DRUG DELIVERY
Fig. 3. Application of nanotechnology in medicine and broad areas of health care.
3066 Int J Pharm Sci Nanotech Vol 9; Issue 1 January February 2016
Diagnostics
The enormous increase in knowledge of the human genome (genomics) and of expression products, proteins (proteomics), makes it possible in an increasing number of cases to trace diseases to abnormalities at the molecular level (Lamerichs et al., 2003). Current methods for the diagnosis and treatment of various diseases are not sufficient because of their poor sensitivity and specificity (Surendiran et al., 2009). Nanotechnology has promising applications in clinical diagnosis due to some of its advantages viz., it is a quick and précised process, requires only small amount of biological samples and provides the possibility of earlier detection of diseases before manifestation of symptoms (Fakruddin et al., 2012).
Nanotechnology facilitates diagnosis at the cellular and molecular levels (both gene and protein). It has promising applications in the field of biomarker discovery, diagnosis of cancer and detection of pathogenic microorganisms (Kewal, 2007). The technology provides precise measure of biological structures such as DNA, RNA and proteins as the size of nanomaterials matches with these functional units (Jain, 2009) (Table 4).
Gold nanoparticles For labeling target ligands/macromolecules
Godfred et al., 2011
Single walled carbon nanotube with field effect transistor (NTFET)
Detection of asthma Agarwal et al., 2012
Superparamagnetic iron oxide particles
Magnetic separation of cancer cells for diagnosis
Monica et al., 2009
Biomarkers play a key role in diagnosis of any disease and pathological conditions. Nanomaterials are suitable for bio-labelling due to their ability to penetrate cell wall and interact with vital components inside and outside the cells. Some of them include quantum dots (QD), magnetic nanoparticles, silver/dendrimer nano-composites, gold nanoparticles etc. (Jain, 2009). This also enables an intracellular imaging of target molecules, which helps in better understanding of pathology. Super paramagnetic contrast agents are being studied intensively as tools for molecular imaging (Weissleder, 1990). Other magnetic resonance imaging (MRI) contrast agents used in diagnosis includes perfluorohydrocarbons (Dayton, 2002) and FePt nanoparticles (Maenosono et al., 2009).
In case of nano chips and microarrays, it is possible to increase the density of combinatorial libraries and they provide high resolution with smaller sample volume
(Hari, 2010). Biosensors constructed out of nanowires and nanocantilevers enables in vitro and in vivo diagnostics. They offer the potential to detect molecular signals that are associated with cancer (Banerjee et al., 2006). As mentioned previously, CNTs, quantum dots (QDs), magnetic and gold nanoparticles have been investigated for their application in biosensors (Suresh et al., 2014). These nano sensors are integrated with biochips for sample analysis. In case of in situ pathogen quantification, bioassay based on conjugated nanoparticle can detect single bacterium within 20 minutes (Zhao, 2004). Nanowires functionalized with antibodies can be used to detect viruses in the sample. Cantilever biosensors enable detection of viruses and bacteria. All these techniques offer label free and multiplex analysis (Chen et al., 2003).
Nanotechnology has greatly supported diagnosis, prevention and understanding of cancer diseases as a whole. A small amount of success in fighting cancer is due to nanotechnology. Nanotechnology transforms cancer diagnosis with its reliability and higher sensitivity. Application of Quantum Dots (QDs) in cancer investigations has significant advantage. The optical activities of these nanocrystals are size dependent and they do not react with cell components (Wu et al., 2003). Atomic force microscopy and QD fluorescent in situ hybridization is used to obtain information on chromosome structure and its abnormalities (Bentolila et al., 2006). The nanoparticles can be used for imaging tumors and the molecules associated with these tumors due to their physical properties (Choi et al., 2006). Rapid detection of genetic mutations (single-nucleotide polymer-phisms) that are associated with cancers can be performed more efficiently using DNA microarrays labeled with gold nanoparticles (Valesca et al., 2009).
Nanotechnology for treatment
Due to its size and targeted effects, today nanotechnology is gaining importance in treatment of various diseases. The nanocarriers can be employed as suitable means to deliver drugs, genes and biomolecules to the organ of interest. Table 5 compiles information on nanoparticle based therapeutics that are clinically approved and used.
Nanotechnology in drug delivery
Major factors that influence the treatment outcome are the efficacy and safety profile of a drug. Currently most of the substances used as medicines are associated with disadvantages such as poor solubility, stability, bioavailability, enzymatic degradation and undesired side effects due to nonspecific distribution (Ochekpe et al., 2009).
Nanotechnology has the potential to refine drug delivery systems that can address several unwanted reactions. They offer suitable means, which focus mainly on targeted delivery of therapeutic agents. Depending on the type of active substance, target organ and the route of administration various nanoparticles can be employed. The active substance can be encapsulated or attached
Geetha et al: Pharmaceutical Nanotechnology: Past, Present and Future 3067
onto the surface of the nanoparticle. Encapsulation of drug within the nanostructures enables protection from early denaturation or degradation and prolongs its
plasma half-life (Navalakhe et al., 2007). Information on different nanocarriers and their application in drug delivery is provided in Table 6.
TABLE 5
Nanoparticle based therapeutics that are clinically approved.
Product name Nanocarrier Applications Manufacturer
Abraxane
Albumin-bound
Various cancers such as breast cancer, non-small cell lung cancer
Celgene
Ambisome Liposomal amphotericin B Fungal infections Gilead sciences Bexxar /monoclonal ab linked with iodine I-131
Radioimmunoconjugate
Used to treat certain forms of non-Hodgkin's lymphoma
Glaxosmithkline
Copaxone
Polymeric nanoparticles (PLGA, PLA)
Multiple sclerosis
Teva Pharmaceutical Industries
Daunoxome Liposome HIV-related kaposi’s sarcoma Gilead sciences, Diatos Doxil PEGylated liposome Ovarian tumor Ortho Biotech Emend Nanocrystalline aprepitant To prevent nausea in cancer patients Merck, Elan Estrasorb
Micelles
To treat certain symptoms of menopause such as hot flashes
Novavax
Feridex Iron oxide nanoparticles In vivo imaging ( liver tumours) Berlex laboratories Myocet
Lipid nanopaticles Metastatic breast cancer Cephalon, Zeneus pharma
Neulasta/ Neulastim
PEG-Granulocyte colony stimulating factor
Neutropenia
Amgen, Roche
Pegasys Polymer protein conjugate Hepatitis Hoffmann-La Roche Oncasper
PEG-L-asparginase / polymer-protein conjugate
Acute lymphoblastic leukemia
Enzon
Rapamune
Nanosuspensions/ Nanocrystalline sirolimus
Immunosuppressant
Wyeth pharmaceuticals
Triglide Nanocrystallized Fenofibrate Treat Lipid disorders Skye pharma Tricor Nanocrystallized Fenofibrate Treat high cholestrol Abbott laboratories Zoladex Polymer rods Suppress sex hormones in the treatment
of prostate and breast cancer Astrazeneca
Lumirem Iron nanoparticles Imaging of abdominal structures Guerbet
TABLE 6
Application of nanotechnology in drug delivery.
Product name Nanocarrier Applications Manufacturer
Abraxane
Albumin-bound
Various cancers such as breast cancer, non-small cell lung cancer
Celgene
Ambisome Liposomal amphotericin B Fungal infections Gilead sciences Bexxar /monoclonal ab linked with iodine I-131
Radioimmunoconjugate
Used to treat certain forms of non-Hodgkin's lymphoma
Glaxosmithkline
Copaxone
Polymeric nanoparticles (PLGA, PLA)
Multiple sclerosis
Teva Pharmaceutical Industries
Daunoxome Liposome HIV-related kaposi’s sarcoma Gilead sciences, Diatos Doxil PEGylated liposome Ovarian tumor Ortho Biotech Emend Nanocrystalline aprepitant To prevent nausea in cancer patients Merck, Elan Estrasorb
Micelles
To treat certain symptoms of menopause such as hot flashes
Novavax
Feridex Iron oxide nanoparticles In vivo imaging ( liver tumours) Berlex laboratories Myocet Lipid nanopaticles Metastatic breast cancer Cephalon, Zeneus pharma Neulasta/ Neulastim
PEG-Granulocyte colony stimulating factor
Neutropenia
Amgen, Roche
Pegasys Polymer protein conjugate Hepatitis Hoffmann-La Roche Oncasper
PEG-L-asparginase / polymer-protein conjugate
Acute lymphoblastic leukemia
Enzon
Rapamune
Nanosuspensions/ Nanocrystallinesirolimus
Immunosuppressant
Wyeth pharmaceuticals
Triglide NanocrystallizedFenofibrate Treat Lipid disorders Skye pharma Tricor NanocrystallizedFenofibrate Treat high cholestrol Abbott laboratories Zoladex Polymer rods Suppress sex hormones in the treatment
of prostate and breast cancer Astrazeneca
Lumirem Iron nanoparticles Imaging of abdominal structures Guerbet
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TABLE 7
Recent developments in the area of nanotechnology application for human wellbeing.
Recent developments Author Inhibition of tumour growth and metastasis by unmodified gold nanoparticles (AuNP). Arvizo et al., 2013 Albumin-based polymeric iron oxide formulations for effective drug delivery system for chemotherapeutics. Enriquez et al., 2013 Design of star-shaped monomethoxy poly (ethylene glycol)-poly (a-caprolactone) (MPEG-PCL) diblock copolymer for the delivery of Doxorubicin to enhance its anticancer activity.
Gao et al., 2013
Superparamagnetic iron oxide nanoparticles coated with chitosan and loaded with ampicillin can act as potential antimicrobial agent.
Hussein et al., 2014
Bioelectrode modified with poly (4-aminophenpol)/AuNPs for the detection of hepatitis B virus. Caetano et al., 2013 Application of antibody conjugated AuNPs in biosensors for the detection of E.coli O157:H7 in feed samples. Ali et al., 2014 Formulation of terpene compounds, α-pinene and linalool with silica nanoparticles (SNPs) to enhance its antifeedant activity against SpodopteralituraF. and Achaea janataL.
Usha Rani et al., 2014
Development of a thermostable β-glucosidase through immobilization on a nanoscale carrier for potential application in biofuel production.
Verma et al., 2013
Construction of acetylcholinesterase (AChE) biosensor, based on tin dioxide nanoparticles (SnO2 NPs), carboxylic graphene and nafion modified glassy carbon electrode for the detection of methyl parathion and carbofuran
Zhou et al., 2013
Active molecules can be delivered to specific organ/tissue by conjugating nanoparticles with targeting molecules such as antibodies or by using magnetic signals. It is crucial in case of chemotherapy, where the drug can be targeted only to malignant tumors while protecting the healthy cells (Fakruddin et al., 2012). Combining MRI contrast agents or radioactive substances with delivery systems provides imaging techniques that enables to monitor the transport of active substance (Jain et al., 2008). After reaching the target site, an active compound has to be released in a controlled and précised manner. Nanodrugs can be designed in such a way that the release occurs only in the presence of special conditions such as temperature, pH or presence of certain enzymes. This is an important property required to achieve targeted drug delivery without causing adverse reactions and toxicity (Shrivastava et al., 2009).
Another advantage of nano-size is, facilitation of drug delivery across certain biological barrier particularly blood brain barrier (BBB). For this purpose, the nanoparticles are provided with target molecules that facilitate interaction with specific receptor-mediated transport systems. It has been reported that polymer based nanoparticles (coated with polysorbate 80) were able to deliver doxoyrubicin and other agents across the BBB for the treatment of brain tumors (Pardridge, 2002).
Gene therapy and nanotechnology
Gene therapy is the introduction of functioning genes into the patient’s cells to treat or prevent a disease. Current gene therapy systems face difficulties such as no effective pharmaceutical processing and development; use of viral vectors may result in unwanted immune response, the engineered mutant may recover their ability to cause disease. A number of strategies have been proposed to address these issues including the application of nanotechnology tools, which facilitates the use of nanoparticle-based non-viral vectors for site-specific gene delivery.
Nanoparticle based gene therapy found to be effective in systemic gene treatment for lung cancer with the use of novel tumor suppressor gene FUS1 (Gopalan et al., 2004).
In vitro studies on nanoparticle mediated gene therapy of p53 in breast cancer cells showed an increased and sustained anti-proliferative activity (Prabha et al., 2004).
Nanotechnology based approach for gene silencing mediated drug addiction therapy was introduced by Bonoiu et al., (2009). They demonstrated that gold nanorod-siRNAnanoplexes can be applied to modulate dopaminergic signalling pathway. Organically modified silica nanoparticles as a non-viral vector have the potential for in vivo gene delivery into the central nervous system (Bharali et al., 2005).
Nanotubes can also be employed in gene therapy because of their ability to transport DNA across biological barriers. Functionalized single-walled carbon nanotubes complexed with siRNA have promising success for silencing gene expression particularly in tumor cells (Zhang et al., 2006). It is also shown that beta-galactosidase marker gene expression was greater through nanotubes when compared to naked DNA (Prato et al., 2008). Therefore, less immunogenic nanosize gene vectors/carriers seem to provide alternate platform for gene therapy in humans.
Tissue regeneration
Tissue engineering could help to repair, create or replace cells, tissues and organs using biomaterials, cells and other factors either alone or in combination. In tissue engineering, for the cells to evolve extracellular matrix (ECM) is required. Cell growth, migration and behavior will be influenced by the interactions between cells and ECM. Nanotechnology provides an alternative platform to fabricate constructs that provides biological substitutes, thus enables to obtain best micro environment for the cells to grow. The fabrication of 3D scaffolds not only offer surface for cell adhesion and growth, but also provide excellent nutrient transmission with their porous network. The important property of nanomaterials is their ability to interact with proteins that control cell functions (Kingsley et al., 2013; Patel, 2011).
Electro spinning is the most widely used technique for the construction of nano-fibrous scaffolds with desired properties and functionality. Hydroxyapatite, collagen,
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chitosan, keratin, polylactic acid (PLA), polyglycolic acid (PGA) are some of the natural and synthetic scaffold materials. These nano-engineered scaffolds have the potential to replace or restore bone, skin, nervous, cardiac and other tissues.
Boland et al., 2004 showed electrospun collagen and elastin nanofibers as efficient scaffolds for the construction of artificial blood vessels. The introduction of nanoparticles of hydroxyapatite directly into damaged bones has found to accelerate the repair (Shrivastava et al., 2009). Scaffolds of carbon can also be employed for osteoblast proliferation (Sahithi et al., 2010). Studies have been reported that nanostructures possess significant properties that aid in neural tissue regeneration. For example, chitosan on polycaprolactone nanofibrous scaffolds provided an excellent mechanical properties that enhanced Schwann cell proliferation (Zhang et al., 2009). MRI contrast agents such as super paramagnetic iron oxide nanoparticles and quantum dots can be employed to track the information on transplanted cells in tissue engineering ( Au et al., 2009; Chen et al., 2007).
Future prospects
The area of nanotechnology is gaining mammoth attention in recent years due to its advantages and ease of applicability. Quite recently, vast amount of significant breakthroughs have been reported on diversified application of nanotechnology in the main areas of environment, agriculture and health. However, we are unable to witness nanomaterials based products or technologies in the area of health and medicine on a broad scale. Scientists involved in nanotechnology research are successful in identifying newer materials that can be used as effective nano tools for addressing unmet modern clinical needs. However, most of them are not commercially available in health care system. However, technology is widely used in the area of electronics and civil engineering section. Few of the pesticides used in agriculture and some therapeutic drugs used in treatment of cancer. The major limitations includes, cost involved in bulk production of the materials or cost of equipment required to use the technology (Nano robots and Nano devices) and ethical issues concerned with pre-clinical and clinical evaluation of new products. Hence, it is essential to focus research and innovation on making cost effective technology, equipment and user friendly aspects in order to make best use of the nanotechnology for the benefit of humanity.
Acknowledgements
Authors would like to acknowledge the support of Gokula Education Foundation (Medical), Bengaluru and Vision Group on Science and Technology, Government of Karnataka for financial assistance through infrastructure grant (KFIST-II) and support for research. Senior author Ms. Geetha M, would like to thank Prof. Channarayappa, Head of the Department, Biotechnology,
MS Ramaiah Institute of Technology, Bengaluru for his encouragement.
References Abu-Salah KM, Ansari AA, and Alrokayan SA (2010). DNA-Based
Applications in Nanobiotechnology. Journal of Biomedicine and Biotechnology 15: 1-15.
Abu-Salah KM(1992). Alteration of the permeability of the human erythrocyte membrane to cations by liposome incorporated amphotericin B. European Journal of ClinicalChemistry and Clinical Biochemistry 30: 737-744.
Agarwal S, and Prajapati R (2012). Nanosensors and their pharmaceutical applications. International journal of pharmaceutical sciences and nanotechnology 4: 1528-1535.
Ali MA, Rehman I, Iqbal A, Din S, Rao AQ, Latif A, Samiullah TR, Azam S, and Husnain T (2014). Nanotechnology, a new frontier in Agriculture. Adv life sci 1: 129-138.
Ali MA, Eldin TAS, Moghazy GME, Tork IM, and Omara II (2014). Detection of E.coli O157: H7 in feed samples using gold nanoparticles sensor. Int J Curr. Microbiol App Sci 3: 697-708.
Ankamwar B, Chaudhary M, and Sastry M (2005). Gold nanotriangles biologically synthesized using tamarind leaf extract and potential application in vapor sensing. Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry 35: 19-26.
Arora S, Sharma P, Kumar S, Nayan R, Khanna PK, and Zaidi MGH (2012). Gold-nanoparticle induced enhancement in growth and seed yield of Brassica juncea. J Plant growth regulation 66: 303-310.
Arvizo RR, Saha S, Wang E, Robertson JD, Bhattacharya R, and Mukherjee P (2013). Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle. Proceedings of the national academy of sciences of the USA 110: 6700-6705.
Au KW, Liao SY, Lee YK. and Lai YH (2009). Effects of Iron Oxide Nanoparticles on Cardiac Differentiation of Embryonic Stem Cells. BiochemBiophys Res Commun 379: 898-903.
Banerjee HN, and Verma M (2006). Use of nanotechnology for the development of novel cancer biomarkers. Expert Rev MolDiagn 6: 679-83.
Bao H, Lu Z, Cui X, Qiao Y, Guo J, Anderson JM, and Li CM (2010). Extracellular microbial synthesis of biocompatible CdTe quantum dots. Actabiomaterialia 6: 3534-3541.
BentolilaLA, and Weiss S (2006). Single-step multicolor fluorescence in situ hybridization using semiconductor quantum dot-DNA conjugates. J Cell BiochemBiophys 45: 59-70.
Bharali DJ, Klejbor I, Stachowiak EK, Dutta P, Roy I, Kaur N, Bergey EJ, Prasad PN, and Stachowiak MK (2005). Organically modified silica nanoparticles: A nonviral vector for in vivo gene delivery and expression in the brain. Proc Natl Acad Sci USA 102: 11539-11544.
Bharani RSA, Namasivayam SKR, and Shankar SS (2014). Biocompatible Chitosan Nanoparticles Incorporated Pesticidal Protein Beauvericin (Csnp-Bv) Preparation for the Improved Pesticidal Activity Against Major Groundnut Defoliator SpodopteraLitura (Fab.) (Lepidoptera; Noctuidae). International Journal of ChemTech Research 6: 5007-5012.
BhawanaP, and Fulekar MH (2012). Nanotechnology: Remediation Technologies to clean up the Environmental pollutants. Res J Chem Sci 2: 90-96.
Bhupinder SS (2014). Nanotechnology in agri-food production: an overview. Nanotechnology, Science and Applications 7: 31-53.
Bielska D, Karewicz A, Kamiński K, Kiełkowicz I, Lachowicz T, Szczubiałka K, and Nowakowska M (2013). Self-organized thermo-responsive hydroxypropyl cellulose nanoparticles for curcumin delivery. J Eur Polym 49: 2485-2494.
Boland ED, Matthews JA, Pawlowski KJ, Simpson DG, Wnek GE, and Bowlin GL (2004). Electrospinning Collagen and Elastin: Preliminary Vascular Tissue Engineering. Front Biosci 9: 1422-1432.
3070 Int J Pharm Sci Nanotech Vol 9; Issue 1 January February 2016
Bonoiua AC, Supriya DM, Dinga H, Roya I, Yonga, Kumara R, Hua R, Bergeya EJ, Schwartzb SA, and Prasada PN (2009). Nanotechnology approach for drug addiction therapy: Gene silencing using delivery of gold nanorod-siRNA nanoplex in dopaminergic neurons. Proc Natl Acad Sci USA 106: 5546-5550.
Brock DA, Douglas TE, Queller DC, and Strassmann JE (2011). Primitive agriculture in a social amoeba. J Nature 469: 393-396.
Caetano L, Costa K, Silva T, Dias L, Rodovalho V, Madurro JM, and Brito-Madurro AG (2014). Use of gold nanoparticles on graphite electrodes functionalized with poly (4-aminophenol) in the development of a bioelectrode for hepatitis B. BMC Proceedings 8: 57 (2014).
Calabretta MK, Kumar A, McDermott AM, and Cai C (2007). Antibacterial activities of poly (amidoamine) dendrimers terminated with amino and poly (ethylene glycol) groups. Biomacromolecules 8: 1807-1811.
Chang YC, Chang SW, and Chen DH (2006). Magnetic chitosan nanoparticles: Studies on chitosan binding and adsorption of Co (II) ions. Reactive & Func Poly 66: 335-341.
Chen DH, and Huang SH (2004). Fast separation of bromelain by polyacrylic acid bound-iron oxide magnetic nanoparticles. Process Biochemistry 39: 2207-2211.
Chen H, Titushkin I, Stroscio M, and Cho M (2007). Altered Membrane Dynamics of Quantum Dot-Conjugated Integrins During Osteogenic Differentiation of Human Bone Marrow Derived Progenitor Cells. Biophysical Journal 92: 1399-1408.
Chen J, Liu M, Zhang L, Zhang J, and Jin L (2003). Application of nanoTiO2 towards polluted water treatment combined with electro-photochemical method. Water Research 37: 3815-3820.
Chen RJ, Bangsaruntip S, Drouvalakis KA, Kam NW, Shim M, and Li Y (2003). Noncovalent functionalization of carbon nanotubes for highly specific electronic biosensors. Proc Natl AcadSci U S A 100: 4984-4989.
Chinnamuthu, CR and Boopathi PM (2009). Nanotechnology and Agroecosystem. Madras Agric J 96: 17-31.
Choe S, Chang YY, Hwang KY, and Khim J (2000). Kinetics of reductive denitrification by nanoscale zero-valent iron. Chemosphere 41: 1307-1311.
Choi J, Jun Y, Yeon S, Kim HC, Shin JS, and Cheon J (2006). Biocompatible heterostructured nanoparticles for multimodal biological detection. J Am ChemSoc 128: 15982-15993.
Choi JH, Kim SD, Noh SH, Oh SJ, and Kim WJ (2006). Adsorption behaviors of nano-sized ETS-10 and Al-substituted-ETAS-10 in removing heavy metal ions, Pb2+ and Cd2+. J Microporous and Mesoporous Materials 87: 163-169.
Christou P, McCabe DE, and Swain WF (1988). Stable Transformation of Soybean Callus by DNA-Coated Gold Particles. Plant Physiol 87: 671-674.
Damge C, Maincent P, and Ubrich N (2007). Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats. Journal of controlled release 117: 163-170.
Dayton PA, and Ferrara KW (2002). Targeted imaging using ultrasound. Journal of Magnetic Resonance Imaging 16: 362-377.
DeRosa MC, Monreal C, Schnitzer M, Walsh R, and Sultan Y (2010). Nanotechnology in Fertilizers. Nat Nanotechnol 5: 91-94.
Enriquez GG, Rizvi SAA, D’Souza MJ, and Do DP (2013). Formulation and evaluation of drug-loaded targeted magnetic microspheres for cancer therapy. Int J Nanomedicine 8: 1393-1402.
Environmental Protection Agency (2007). US Environmental Protection Agency Report EPA 100/B-07/001 EPA Washington DC.
Fakruddin M, Hossain Z, and Afroz H (2012). Prospects and applications of nanobiotechnology: a medical perspective. Journal of nanobiotechnology 10: 1-8.
Feng J, Hu X, Yue PL, Zhu HY, and Lu GQ (2003). Degradation of azo-dye orange II by a photoassisted fenton reaction using a novel composite of iron oxide and silicate nanoparticles. Ind Eng Chem Res 42: 2058-2066.
Floriano PN, Christodoulides N, Miller CS, Ebersole J, Spertus J, Rose BG, Kinane DF, Novak MJ, Steinhubl S, Acosta S, Mohanty S, Dharshan P, Yeh C, Redding S, Furmaga W, and McDevitt JT (2009). Use of Saliva-Based Nano-Biochip Tests for Acute Myocardial Infarction at the Point of Care: A Feasibility Study. Clinical Chemistry 55: 1530-1538.
Forim MR, Costa ES, Das GF, Fernandes JB, Mondego JM, and Junior ALB (2013). Development of a new method to prepare nano-/microparticles loaded with extracts of Azadirachtaindica, their characterization and use in controlling Plutellaxylostella. J Agric Food Chem 61: 9131-9139.
Forssen E, and Willis M (1998). Ligand-targeted liposomes. Adv drug delivery rev 29: 249-271.
Gao X, Wang B, Wei X, Wang Rao W, Ai F, Zhao F, Men K, Yang B, Liu X, Huang M, Gou M, Qian Z, Huang N, and Wei Y (2013). Preparation, characterization and application of star-shaped PCL/PEG micelles for the delivery of doxorubicin in the treatment of colon cancer. Int J Nanomedicine 8: 971-982.
Godfred A Menezes, Priyadharshini S Menezes, and Cylma Menezes (2011). Nanoscience in diagnostics. Internet Journal of Medical Update 6: 16-23.
Gopalan B, Ito I, Branch CD, Stephans C, Roth JA, and Ramesh R (2004). Nanoparticle Based Systemic Gene Therapy for Lung Cancer: Molecular Mechanisms and Strategies to Suppress Nanoparticle-Mediated Inflammatory Response. Technol Cancer Res Treat 3: 647-657.
Gradishar WJ, Tjulandin S, and Davidson N (2005). Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. Journal of clinical oncology 23: 7794-7803.
Hari M (2010). Nanobiotechnology: Bio Inspired Devices and Materials of the future. J Bio sci Res 1: 108-117.
Hussein MZ, Hussein-Al-Ali SH, Zowalaty MEE, B Geilich BM, and Webster TJ (2014). Synthesis, characterization, and antimicrobial activity of an ampicillin conjugated magnetic nanoantibiotic for medical applications. Int J Nanomedicine 9: 3801-3814.
Ingale AG, and Chaudhari AN (2013). Biogenic synthesis of nanoparticles and potential applications: An eco-friendly approach. J Nanomed Nanotechol 4: 165.
Jain KK (2009). Role of nanobiotechnology in the development of personalized medicine. Nanomedicine 4: 249-252.
Jain TK, Richey J, Strand M, Leslie-Pelecky DL, Flask CA, and Labhasetwar V (2008). Magnetic nanoparticles with dual functional properties: drug delivery and magnetic resonance imaging. Biomaterials 29: 4012-4021.
Jain and Devendra (2009). Synthesis of plant-mediated silver nanoparticles using papaya fruit extract and evaluation of their anti-microbial activities. Digest journal of nanomaterials and biostructures 4: 557-563.
Jerobin J, Sureshkumar RS, Anjali CH, Mukherjee A, and Chandrasekaran N (2012). Biodegradable polymer based encapsulation of neem oil nanoemulsion for controlled release of Aza-A. CarbohydrPolym 90: 1750-1756.
Karunakaran G, Suriyaprabha R, Manivasakan P, Yuvakkumar R, Rajendran V, Prabu P, and Kannan N (2013). Effect of nanosilica and silicon sources on plant growth promoting rhizobacteria, soil nutrients and maize seed germination. J IET Nanobiotechnol 7: 70-77.
KeawchaoonL, and Yoksan (2011). Preparation, characterization and in vitro release study of carvacrol loaded chitosan nanoparticles. Colloids Surf B Biointerfaces 84: 63-71.
Kewal KJ (2007). Applications of Nanobiotechnology in Clinical Diagnostics. Clinical Chemistry 53: 2002-2009.
Khodakovskaya M, Dervishi E, Mahmood M, Xu Y, Li Z, Watanabe F, and Biris AS (2009). Carbon nanotubes are able to penetrate
Geetha et al: Pharmaceutical Nanotechnology: Past, Present and Future 3071
plant seed coat and dramatically affect seed germination and plant growth. J Advancements in life sciences 3: 3221-3227.
Kingsley JD, Ranjan S, Dasgupta N, and Saha (2013). Nanotechnology for tissue engineering: Need, techniques and applications. Journal of pharmacy research 7: 200-204.
Kuang Y, Wang Q, Chen Z, Megharaj M, and Naidu R (2013). Heterogeneous Fenton-like oxidation of monochlorobenzene using green synthesis of iron nanoparticles. Journal of Colloid and Interface Science 410: 67-73.
Kulkarni S. S (2013). Bhasma and nanomedeicine. International research journal of pharmacy 4: 10-16.
Lamerichs R, Schaffter T, Hamisch Y, and Powers J (2003). Molecular imaging: the road to better healthcare. Medica-Mundi 47: 2-9.
Lao S. B, Zhang Z. X, Xu H. H and Jiang G. B. (2010). Novel amphiphilic chitosan derivatives: synthesis, characterization and micellar solubilization of rotenone. CarbohydrPolym 82: 1136-1142.
Lee Ventola C (2012). The Nanomedicine Revolution Part 2: Current and Future Clinical Applications. P & T 37(10): 582-591.
Lengke M. F, Sanpawanitchakit C and Southam G (2011). Biosynthesis of gold nanoparticles: a review, Metal Nanoparticles in Microbiology. 1st edn, Springer, New York 112: 37-74.
Li Y, Cu Y. T and Luo D (2005). Multiplexed detection of pathogen DNA with DNA based Fluorescence nanobarcodes. Nat Biotechnol 23: 885-889.
Liou Y. H, Lo S. L, Lin C. J, Hu C. Y, Kuan W. H, and Weng S. C. (2005). Methods for accelerating nitrate reduction using zero valent iron at near neutral pH: Effects of H2-reducing pretreatment and copper deposition. Environ. Sci. Technol 39: 9643-9648.
Lu W, Qin X, Liu S, Chang G, Zhang Y, Luo Y and Sun X (2012). Economical, green synthesis of fluorescent carbon nanoparticles and their use as probes for sensitive and selective detection of mercury (II) ions. Analytical chemistry 84(12): 5351-5357.
Maenosono S, Suzuk T. I, Saita S (2009). SuperparamaganeticFePt nanoparticles as excellent MRI contrast agents. Jounal of Magnetism and Magnetic materials 320: 79-83.
Makarova O. V, Rajh T, Thurnauer M. C, Martin A, Kemme P. A and Cropek D (2000). Surface modification of TiO2 nanoparticles for photochemical reduction of nitrobenzene.Environ. Sci. Technol 34: 4797-4803.
Mansoori G. A. (2002). Advances in atomic and molecular nanotechnology, United Nations Tech Monitor, UN-APCTT Tech Monitor, Issue: 53-59.
Mishra V. K, Dwivedi D. K and Mishra U. S (2013). Emerging Consequence of Nanotechnology in Agriculture: An Outline. Trends in Biosciences 6: 503-506.
Mohanpuria P, Rana K. N and Yadav S. K (2008). Biosynthesis of nanoparticles: technological concepts and future applications. Journal of Nanoparticle Res 10: 507-517.
Monalisha Rath, Swati S Panda and Nabin K Dhal (2014). Synthesis of silver nano particles from plant extract and its application in cancer treatment: a review. International journal of plant animal and environmental sciences 4: 137-145.
Monica T, Russell PJ, and Khatri A (2009). Magnetic nanoparticles: prospects in cancer imaging and therapy. Discovery medicine 38: 68-74.
Narayanan S, Sathy BN, Mony U, Koyakutty M, Nair SV, and Menon D (2011). Biocompatible magnetite/gold nanohybrid contrast agents via green chemistry for MRI and CT bioimaging. ACS applied materials & interfaces 4: 251-260.
Navalakhe RM, and Nandedkar TD (2007). Application of nanotechnology in biomedicine. Indian journal of experimental biology 45: 160-165.
Norton S (2008). A brief history of potable gold. MolInterv 8: 120-125.
Nutt MO, Hughes JB, and Wong M S (2005). Designing Pd-on-Au Bimetallic Nanoparticle Catalysts for Trichloroethene
Ochekpe NA, Olorunfemi PO, and Ngwuluka NC (2009). Nanotechnology and Drug delivery: Background and applications. Tropical journal of pharmaceutical research 8: 265-274.
Ong YT, Ahmad AL, Zein SHS, and Tan SH (2010). A review on carbon nanotubes in an environmental protection and green engineering perspective. Brazilian Journal of Chemical Engineering 27: 227-242.
Pal D, Sahu CK, and Haldar A (2014). Bhasma: the ancient Indian nanomedicine. Journal of advanced pharmaceutical technology & research 5: 4-12.
Pardridge W M (2002). Drug and gene targeting to the brain with molecular Trojan horses. Nat Rev Drug Discov 1: 131-139.
Parida UK, Bindhani BK, and Nayak P (2011). Green synthesis and characterization of gold nanoparticles using onion (Allium cepa) extract. World Journal of Nano Science and Engineering 1: 93-98.
Patel D (2011). Regenerative Medicine Using Nanotechnology: A Review. International Journal of Pharmaceutical & Biological Archives 2: 1033-1039.
Prabha S, and Labhasetwar V (2004). Nanoparticle-mediated wild-type p53 gene delivery results in sustained antiproliferative activity in breast cancer cells. J Mol Pharmacol 1: 211-219.
Prasad R, Kumar V, and Prasad KS (2014). Nanotechnology in sustainable agriculture: Present concerns and future aspects. African journal of biotechnology 13: 705-713.
Prato M, Kostarelos K, and Bianco A (2008). Functionalized carbon nanotubes in drug design and discovery. AccChem Res 41: 60-68.
Rath M, Swati SP, and Dhal NK (2014). Synthesis of silver nano particles from plant extract and its application in cancer treatment: a review. International journal of plant, animal and environmental sciences 4: 137-145.
Renugadevi K, Inbakandan D, Bavanilatha M, and Poornima V (2012). CissusQuadrangularis Assisted Biosynthesis of Silver Nanoparticles with Antimicrobial and Anticancer potentials. Int J Pharm Bio Sci 3: 437-445.
Roco MC (2004). The US national nanotechnology initiative after 3 years (2000-2003). J Nanoparticle Res 6: 1-10.
Sahithi K, Swetha M, Ramasamy K, Srinivasan N, and Selvamurugan N (2010). Polymeric composites containing carbon nanotubes for bone tissue engineering. Int J Biol Macromol 46: 281-283.
Sarojini S, Rajasekar S, and Koumaravelou K (2010). Carbon nanotubes: a new weapon in health care treatment. Int Journal of Pharma and Bio sciences 1: 644-649.
Shrivastava S, and Debabrata D (2009). Applying nanotechnology to human health: Revolution in biomedical science. J of nanotechnology 1-14.
Sindhura KS, Prasad TNVKV, Selvam PP, and Hussain OM (2014). Synthesis, characterization and evaluation of effect of phytogenic zinc nanoparticles on soil exo-enzymes. J Appl Nanosci 4: 819-827.
Song, Yong J, Kwon E, and Kim BS (2010). Biological synthesis of platinum nanoparticles using Diopyros kaki leaf extract. Bioprocess and biosystems engineering 33: 159-164.
Srivastava A, Srivastava ON, Talapatra S, Vajtai R, and Ajayan PM (2004). Carbon nanotubes filters. Nature Materials 3: 610-614.
Stathatos E, Tsiourvas D, and Lianos P (1999). Titanium dioxide films made from reverse micelles and their use for the photocatalytic degradation of adsorbed dyes. J Colloids and Surfaces A: Physicochemical and Engineering Aspects 149: 49-56.
Suehiro J, Zhou G, and Hara M (2005). Detection of partial discharge in SF6 gas using a carbon nanotube-based gas sensor. Sensors and Actuators, B: Chemical 105: 164-169.
Surendiran A, Sandhiya S, Pradhan SC, and Adithan C (2009). Novel applications of nanotechnology in medicine. Indian J Med Res 130: 689-701.
3072 Int J Pharm Sci Nanotech Vol 9; Issue 1 January February 2016
Suresh S, and Periasamy M (2014). Recent trends in nanobiosensors and their applications. RevAdvMater Sci 36: 62-69.
Tahaikt M, Habbani RE, AitHaddou A, Achary I, Amor Z, Taky M, Alami A, Boughriba A, Hafsi M, and Elmidaoui A (2007). Fluoride removal from groundwater by nanofiltration. Desalination 212: 46-53.
Thakur M and Saikhedkar NK (2013). BehavioralModeling and Simulation with Experimental Analysis of a Two Stroke Engine Using Nanosized Copper Coated Catalytic Converter. International Journal of Advanced Science and Technology 59: 97-112.
Thompson TD (2007). Using gold nanoparticles for catalysis. Nano Today 2: 40-43.
Torney F, Trewyn BG, Lin VS, and Wang K (2007). Mesoporous silica nanoparticles deliver DNA and chemicals into plants. Nat Nanotechnol 2: 295-300.
Ueda T, Bhuiyan MMH, Norimatsu H, Katsuki S, Ikegami T, and Mitsugi F (2008). Development of carbon nanotube-based gas sensors for NOx gas detection working at low temperature. Physica E: Low-dimensional Systems and Nanostructures 40: 2272-2277.
Usha RP, Madhusudhanamurthy J, and Sreedhar B (2014). Dynamic adsorption of a-pinene and linalool on silica nanoparticles for enhanced antifeedant activity against agricultural pests. J Pest Sci 87: 191-200.
Valesca PR, Hummel MJM, and Harten WHV (2009). Review on early technology assessments of nanotechnologies in oncology. J Molecular oncology 3: 394-401.
Verma ML, Chaudhary R, Tsuzuki T, Barrow CJ, and Puri M (2013). Immobilization of b-glucosidase on a magnetic nanoparticle improves thermostability: Application in cellobiose hydrolysis. J BioresourceTechnology 135: 2-6.
Wang CB, and Zhang WX (1997). Synthesizing Nanoscale Iron Particles for Rapid and Complete Dechlorination of TCE and PCBs. Environ SciTechnol 31: 2154-2156.
Wang L, and Wang A (2007). Adsorption characteristics of Congo red onto the chitosan/montmorillonite nanocomposite. J Hazard. Mater 147: 979-985.
Wang X, Chen C, Liu H, and Ma J (2008). Characterization and Evaluation of Catalytic Dechlorination Activity of Pd/Fe Bimetallic Nanoparticles. Ind. Eng. Chem. Res 47: 8645-8651.
Weissleder R, Elizondo G, Wittenberg J, Rabito CA, Bengele HH, and Josephson L (1990). Ultra small superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology 175: 489-493.
Wu X, Liu H, and Liu J (2003). Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. J Nature Biotechnology 21: 41-46.
Xiao Y, Patolsky F, Katz E, Hainfeld JF and Willner I (2003). Plugging into enzymes: nanowiring of redox enzymes by a gold nanoparticles. J Science 299: 1877-1881.
Yang F, Hong F, You W, Liu C, Gao F, Wu C, and Yang P (2006). Influence of nano-anatase TiO2 on the nitrogen metabolism of growing spinach. J Biological trace element research 110: 179-190.
Yang FL, Li X, Zhu F, and Lei C (2009). Structural Characterization of Nanoparticles Loaded with Garlic Essential Oil and Their Insecticidal Activity against Tribolium-castaneum (Herbst) (Coleoptera: Tenebrionidae). J Agric Food Chem 57: 10156-10162.
ZenuJha, Behar N, S Sharma SN, Chandel G, Sharma DK, and Pandey MP (2011). Nanotechnology: Prospects of Agricultural Advancement. Nano Vision 1: 88-100.
Zhang L, and Webster TJ (2009). Nanotechnology and Nanomaterials: Promises for Improved Tissue Regeneration. Nanotoday 4: 66-80.
Zhang WX (2003). Nanoscale iron particles for environmental remediation: An overview. Journal of Nanoparticle Research 5: 323-332.
Zhang Z, Yang X, Zhang Y, Zeng B, Wang S, Zhu T, Roden RBS, Chen Y, and Yang R (2006). Delivery of Telomerase Reverse Transcriptase Small Interfering RNA in Complex with Positively Charged Single-Walled Carbon Nanotubes Suppresses Tumor Growth. Clin Cancer Res 12: 4933-4939.
Zhao X, Hilliard LR, Mechery SJ, Wang Y, Bagwe RP, and Jin S (2004). A rapid bioassay for single bacterial cell quantification using bioconjugated nanoparticles. Proc Natl Acad Sci U S A 101: 15027-15032.
Zhou Q, Yang L, Wang G, and Yang Y (2013). Acetylcholinesterase biosensor based on SnO2 nanoparticles–carboxylicgraphene–nafion modified electrode for detection of pesticides. J Biosensors and Bioelectronics 49: 25-31.
Address correspondence to: Dr. K.N. Chidambara Murthy, Principal Scientist, Central Research Laboratory, MS Ramaiah Medical College and Hospitals MSRIT Post, Bengaluru- 560 054, India. Ph: +91-080-40502772; E-mail: [email protected]
