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Colloids and Surfaces A: Physicochemical andEngineering Aspects
journa l h omepa g e: www.elsev ier .com/ locate /co lsur fa
anoparticles as delivery vehicles for sunscreen agents
ei Shia,1, Jingning Shanb, Yiguang Jub, Patricia Aikensc, Robert K. Prud’hommea,∗
Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ 08544, USADepartment of Mechanical and Aerospace Engineering, Princeton University, Princeton, NJ 08544, USABASF Corporation, Tarrytown, NY 10591, USA
r t i c l e i n f o
rticle history:eceived 6 September 2011eceived in revised form2 December 2011ccepted 15 December 2011vailable online 24 December 2011
eywords:anoparticleunscreenV filterolymer
a b s t r a c t
Sunscreen filters, which block hazardous UV radiation, are commonly applied in cosmetic products toprotect the skin, the hair, or the product itself. Most sunscreen formulations are emulsions or creams.However, formulations based on nanoparticles as the delivery vehicle for the sunscreen compoundspotentially have advantages in terms of retention on the skin, lack of penetration across the epider-mal layer and UV attenuation by both absorption and scattering. In this study, sunscreen nanoparticlesuspensions are prepared via the novel Flash NanoPrecipitation process (FNP), which involves rapidmicromixing followed by block copolymer directed assembly of nanoparticles. The block copolymer sta-bilizer is polystyrene-block-polyethylene glycol (PS-b-PEG) with a homopolymer polystyrene (PS) as theco-solute in the nanoparticle core. By changing the filter and/or PS concentration, stable nanoparticleswith sizes from 80 to 200 nm are prepared. Most importantly, FNP enables incorporation of both organicand inorganic hydrophobic filters into nanoparticles, and thus offers broad-spectrum sun protection. Thenanocolloids offer enhanced UV protection because they attenuate light by both adsorption and scat-tering. Three organic filters, ethylhexyl triazone (Uvinul T 150), benzophenone-3 (Uvinul M 40), anddiethylamino hydroxybenzoyl hexyl benzoate (Uvinul A Plus) and two nano-sized inorganic filters, zinc
oxide and titanium dioxide are examined. In addition it is found the polystyrene core material offerssignificant UV blocking in the UVC range of 200–280 nm. Dynamic light scattering (DLS) reveals that thenanoparticles’ size distribution is narrow and remains stable (over 80 days). The combination of organicand inorganic filters enables tunable UV protection over the wavelength range 280–400 nm. In conclu-sion, flash nanoprecipitation provides a new formulation method of encapsulating hydrophobic organicand inorganic sunscreen filters.
. Introduction
Overexposure of human skin to ultraviolet radiation (UV) fromhe sun is a major risk factor for sunburn and the developmentf skin cancer. Hazardous UV light is generally divided into threeand regions: low-energy UVA (with wavelength of 320–400 nm),igh energy UVB (280–320 nm) and UVC (200–280 nm) [1]. UVC
egion is mostly absorbed by the atmospheric ozone layer andence is of less concern from a health perspective. To preventhoto damage by UV light, a wide variety of topical sunscreen prod-
Abbreviations: NP, nanoparticle; FNP, flash nanoprecipitation; MIVM, multi-ortex inlet mixer; PS, polystyrene; PS-b-PEG, polystyrene-block-polyethylenelycol.∗ Corresponding author at: Department of Chemical & Biological Engineering,301 EQUAD, Princeton University, Princeton, NJ 08544 USA. Tel.: +1 609 258 4577;
ucts have been developed. There are two basic types of UV filtersused as the active ingredient in sunscreen products. Organic filters,depending on their chemical structures, can absorb UV radiationof specific wavelengths. Inorganic filters such as titanium dioxideand zinc oxide can absorb and scatter UV radiation, and so havea broader UV blocking range than the organics. The performanceof a sunscreen formulation relies not only on the physicochemi-cal properties of the filters encapsulated, but also on the carrierused to deliver them. In recent years, nanoparticles, as a carrier sys-tem for delivering sunscreens, have attracted significant attention.For example, Muller and coworkers introduced solid lipid nanopar-ticles (SLNs) to encapsulate oxybenzone using cetyl palmitate orother crystalline lipids by high pressure homogenization [2–4].Similarly, carnauba wax-based SLNs were used to incorporate theinorganic filter, titanium dioxide, by Müller-Goymann et al. [5,6].Another emulsion approach, so called “salting out” technique was
adopted by Vettor et al. and Alvarez-Román et al. to produce octyl-methoxycinnamate loaded polymeric nanoparticles [7–9]. Morerecently, Loy et al. reported the synthesis of organosilica sunscreennanoparticles by emulsion polymerization [10]. Nanoparticles have
hown significant advantages over the conventional delivery sys-ems involving soluble forms of delivery such as creams, sprays, andels. Nanoparticles effectively protect labile organic filters againsthemical degradation by entrapping them inside the particle corenstead of molecularly dissolving them either in an oil or a waterhase [11]. Soluble formulations only take advantage of light atten-ation by adsorption. Nanoparticle carriers attenuate light by bothdsorption and scattering. However, since scattering increases ashe sixth power of particle size, microparticle homologues, can pro-uce undesirable “white” residue, as found in the older zinc oxideunscreen formulations. Therefore, close control of nanoparticleize distribution is required as well as optimization of size to enableome attenuation by scattering but to prevent opacity.
Current methods employed for the production of sunscreenanoparticles face the following limitations. High pressure homog-nization requires high energy inputs to melt lipids and to createolid/liquid interfaces. Multiple preparative steps are involved. Thesalting out’ technique is compromised by the usage of high con-entration of stabilizer and often suffers from a broad particle sizeistribution [12]. Finally, copolymerization of organic filters intoanoparticles requires covalent bond formation and therefore theesulting sunscreen is no longer among those approved by the USDA for topical use. The approval process of new molecular entitiesan be costly and uncertain. Therefore, there is an increasing needor a simple, robust and easily adaptable solution for fabricatingunscreen nanoparticles, and especially for a process that enableshe co-incorporation of organic and inorganic sunscreens.
Flash NanoPrecipitation (FNP) is a new technology for the prepa-ation of multifunctional nanoparticles (NPs) via rapid solventisplacement using amphiphilic diblock copolymers to direct pre-ipitation of hydrophobic species. The process is composed ofwo steps: (1) the hydrophobic actives along with amphiphiliciblock copolymers are dissolved in a water miscible organic sol-ent such as tetrahydrofuran or acetone; and (2) the organichase is rapidly mixed with an antisolvent (water) in a multi-
nlet vortex mixer (MIVM) to create homogeneous mixing on therder of milliseconds. Details of the design of the MIVM appara-us have been described elsewhere [13–15]. In the process, highupersaturation is induced by the rapid mixing which drives theydrophobic actives and the hydrophobic block of the copolymer torecipitate simultaneously. All hydrophobic components are kinet-
cally trapped in the core. The NPs are sterically stabilized by theydrophilic block of the copolymer as it precipitates onto the sur-
ace of the aggregating core components. The block copolymerdsorption arrests aggregation, affording nanoparticles with nar-ow size distributions. In contrast to slow equilibrium processes,NP offers high loading capacity, control over size and incorpora-ion of multiple actives in the same nanoparticle. A wide range ofuccessful applications of FNP have been demonstrated for encap-ulation of various hydrophobic drugs, peptides, imaging agents, or
combination of both therapeutics and inorganic colloids [16–20].The present work employs FNP for the preparation and opti-
ization of polymeric sunscreen NPs. Three widely used organiclters, Uvinul A Plus, T 150 and M 40, are selected to achieve desiredpectral absorbance (Fig. 1). Also, to realize broad band UV block-ng, surface-modified titanium dioxide and zinc oxide nanocrystalsre synthesized and encapsulated in polymeric NPs. The combina-ion of titanium dioxide with organic filters generates compositePs which show a synergistic sunscreen effect. The combinationnables tuning of UV absorption over the UVA and UVB range withhe advantage of blockage by scattering in addition to intrinsic UVbsorption. The size, size distribution and UV blocking of NPs are
tudied using dynamic light scattering and UV–vis spectroscopy.n addition, the styrenic block of the polystyrene-b-polyethylenelycol, which is used as the protecting copolymer is found to ben intrinsic UV blocker. The results presented are intended to
hem. Eng. Aspects 396 (2012) 122– 129 123
demonstrate the wide applicability of FNP and provide a new stableNP carrier system for sunscreen formulations.
2. Materials and methods
2.1. Materials
Diethylzinc (Zn(Et)2), titanium(IV) isopropoxide (TTIP),octadecene, oleic acid, hexadecyl amine, and ethanol werepurchased from Sigma–Aldrich (St. Louis, MO, USA). HPLC gradetetrahydrofuran (THF) containing no preservatives was purchasedfrom Fisher Scientific (Pittsburgh, PA, USA). All reagents andsolvents were used as received. Deionized water with a resistivityof 18 M� cm was obtained using Milli-Q Water System (Millipore,Billerica, MA, USA) and was used for NP preparation and dialysis.
Diblock copolymer, polystyrene-b-polyethylene glycol (PS-b-PEG, MW: 1.5k-b-5k), and homopolymer, polystyrene (PS, MW:1.5k), were synthesized by anionic polymerization as reported pre-viously [21].
Organic UV filters, Uvinul A Plus (diethylamino hydroxyben-zoyl hexyl benzoate), Uvinul T150 (ethylhexyl triazone) and UvinulM40 (oxybenzone) were provided by BASF (Tarrytown, NY, USA).Reported nonhydrolytic approaches were applied to the synthesisof inorganic UV filters, zinc oxide (ZnO) and titanium dioxide (TiO2)colloidal nanocrystals [22,23]. In a typical synthesis of ZnO, 15 mL ofoctadecene and 2 mL of oleic acid were heated at ∼100 ◦C under vac-uum for 30–40 min. The solution was degassed with nitrogen threetimes (2–3 min each time) to remove oxygen. Then, the solutionwas heated to 250 ◦C and 0.45 mL diethylzinc was quickly injected.The reaction was heated for 15 min under nitrogen. Subsequently,the solution was cooled to room temperature and excess ethanolwas added to yield the product as a white precipitate, which wascollected by centrifugation and dried in high vacuo. Synthesis ofTiO2 nanocrystals was similar to the above procedure except usingtitanium(IV) isopropoxide as the TiO2 precursors and hexadecy-lamine instead of oleic acid as the coordination ligand.
2.2. Methods
2.2.1. Transmission electron microscopy (TEM)Images of ZnO were obtained using a LEO/Zeiss 910 TEM (Carl
Zeiss, Thornwood, NY, USA) equipped with a PGT-IMIX EDX system(100 keV). With a field-emission-gun, this microscope provides apoint-to-point resolution of 0.2 nm and an electron probe of 0.7 nmwith energy up to 200 keV. Images of TiO2 were taken on a Zeiss 912AB TEM (Carl Zeiss, Thornwood, NY, USA) equipped with an OmegaEnergy Filter. Micrographs were captured using a digital camerafrom Advanced Microscopy Techniques.
2.2.2. Polymeric nanoparticle (NP) formulationBlock copolymer NPs were prepared using the Flash Nano-
Precipitation (FNP) technique. A representative NP preparationincorporating precoated inorganic nanostructures is described asfollows. 60 mg of PS-b-PEG, 15 mg Uvinul A Plus, and 15 mg ofTiO2 were dissolved in 3 mL of THF. The organic solution was fed(12 mL/min, one stream), along with deionized water (40 mL/minfor each of three streams), into a four-stream MIVM using twodigitally controlled syringe pumps (Harvard Apparatus, PHD 2000programmable, Holliston, MA, USA) to yield the NP suspension witha solvent composition of 1:10, v/v THF/water. NPs were then dia-
lyzed 4 times against 4 L of deionized water using a Spectra/Pormembrane bag with MWCO of 6000–8000 Da (Spectrum Laborato-ries Inc, Rancho Dominguez, CA, USA) at room temperature for 16 hto remove THF and stored at 4 ◦C.
124 L. Shi et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 396 (2012) 122– 129
O OH
O
Benzophen one-3 (Uvinul M 40)N
N
N
HN
NHNH
O
O
OO
O
O
Diethylamino hyd roxy benzoyl hexy lbenzoate (Uvinul A Plus)
OOH
N
O O
Ethylhexy l triazo ne (Uvinul T 150)
Fig. 1. Molecular structure of Uvinul A Plus, T 150 and M 40.
Fig. 2. DLS size distribution of sunscreen nanoparticles. (a) A Plus-1, (b) A Plus-2, (c) T 150-1, (d) T 150-2, and (e) M 40. Data are displaced vertically for clarity. From bottomto top: immediately after FNP, after dialysis, after 80 days of storage.
L. Shi et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 396 (2012) 122– 129 125
F Plus-t = 0.4 m1 g/mL
2
dIatarw
2
a
TCfo
ig. 3. UV–vis absorption spectra of sunscreen nanoparticle suspensions. (a) Ao [solid] = 0.13 mg/mL ([A Plus] = 0.032 mg/mL), (c) T 150-1, diluted to [solid]
50] = 0.022 mg/mL), and (e) M 40, diluted to [solid] = 0.173 mg/mL ([M 40] = 0.043 m
.2.3. Characterization of nanoparticle (NP) dispersionsNP size and size distributions were measured at 25 ◦C via
ynamic light scattering (DLS) using a ZetaSizer Nano ZS (Malvernnstruments, Worcestershire, UK). The instrument operates at
backscatter detection angle of 173◦. Sizes and size distribu-ions were calculated using the Malvern cumulants deconvolutionlgorithm of the autocorrelation function. The distributions areeported using the normal resolution mode and the intensityeighted distribution is reported.
.2.4. UV absorbance of nanoparticle (NP) dispersionsUV absorbance spectra of NPs were collected at room temper-
ture by an Evolution 300 UV–visible Spectrophotometer (Thermo
able 1haracteristics of organic sunscreen NPs. Loading values are defined with respect to the
rom the cumulants analysis of the autocorrelation function, and the polydispersity indef the particle distribution.
1, diluted to [solid] = 0.46 mg/mL ([A Plus] = 0.003 mg/mL), (b) A Plus-2, dilutedg/mL ([T 150] = 0.036 mg/mL), (d) T 150-2, diluted to [solid] = 0.67 mg/mL ([T).
Electron Corporation, Madison, WI, USA) in the wavelength range200–500 nm, with a resolution of 1 nm. Samples were measured ina quartz cuvette with a path length of 1 cm.
3. Results and discussion
3.1. Encapsulation of organic filters
Three organic filters, A Plus, T 150 and M 40 are selected to
correspondingly absorb UVA, UVB and broad band radiation. Withthe FNP technique using the MIVM, sunscreen NPs were formu-lated as shown in Table 1. Polystyrene (PS) was used as an inertco-solute to form NP cores stabilized by the diblock copolymer,
total solids in the composite nanoparticle. The mean size is the diameter reportedx (PDI) is determined from the cumulants analysis and is a measure of the breadth
ymer loading (wt%) Solids in NP suspension (mg/mL) Mean size (nm) PDI
Fig. 4. DLS size distribution and UV–vis absorption spectra of PS nanoparticles.(a) size distribution, (b) PS-1, [solid] = 1.18 mg/mL ([PS] = 0.48 mg/mL), (c) PS-2,[solid] = 1.36 mg/mL (PS] = 0.66 mg/mL), and (d) PS-3, diluted to [solid] = 0.61 mg/mL
26 L. Shi et al. / Colloids and Surfaces A: Ph
S-b-PEG. Filter loading is defined as the solid weight percentagef filter in the NP (i.e. filter weight divided by total filter, PS and PS--PEG weight). The listed intensity averaged diameters of the NPsere measured by DLS after dialysis. In all cases, narrow size dis-
ributions are achieved with polydispersity index (PDI) values lesshan 0.26. The polydispersity index is defined from moments of theumulant fit of the autocorrelation function and is calculated by thenstrument software [24]. The NPs, except M 40, remain stable for
months (i.e. the duration of this set of experiments) when storedt 4 ◦C, as proved by both DLS and UV absorption results (Fig. 2).he sizes of the organic-based NPs are determined by the precip-tation of the hydrophobic core; therefore, increasing the loadingf T 150 from 9% to 33% wt increased the NP size from 145 nm to56 nm. Therefore, stable NPs in the size range of 100–350 nm cane conveniently produced by the FNP process.
The UV attenuation of the sunscreen NPs is shown in Fig. 3. Theispersions are diluted with water to achieve measurable UV–visbsorbance. The extinction coefficients of A Plus, T 150, and M 40re 940, 1585, and 613 (g/100 mL)−1 cm−1, respectively, at theireak absorption wavelengths [25–27]. In NPs, the efficiency of the
Plus filter is comparable to the T 150 filter. As shown in Fig. 3bnd d, for A Plus the peak absorbance is AU = 1.86 at a core weightoading of 25% and [A Plus] = 0.032 mg/mL, compared to AU = 1.38or the 33% loaded T 150 sample at [T 150] = 0.022 mg/mL.The M0 filter is very effective in the UVB range (280–320 nm), whereas
150 and A Plus-1 are less effective in blocking UVB. They havetronger UVA absorbance. However, the M 40 NPs were unstableith time as shown in Fig. 3e. The NP size decreases from 157 nm
o 142 nm during dialysis, and the UV absorbance decreases dur-ng initial dialysis and upon storage. This results from the loss of
40 from the nanoparticle cores into large macroscopic crystalshich rapidly settle and are not sampled when the dispersion is
emoved for UV analysis. So M 40 is not a viable candidate forolid NP formulations.The importance of scattering on UV atten-ation was demonstrated for NPs without specific filter materials,
.e. they contained only PS homopolymer in the NP core. Manip-lating the PS concentration (23, 33, 50 wt% with respect to totalP mass) provides PS NPs with diameters of 51, 87, and 125 nm
See Fig. 4a). The corresponding UV–vis absorbance spectra of PSPs are shown in Fig. 4b–e. The PS NPs are quite stable withoutbvious size or UV absorbance change during long time storage.nterestingly, PS in both the core and the hydrophobic block of thetabilizing polymer acts as an intrinsic UV blocker, especially in theVC range (200–280 nm). The absorbance at 260 nm increases from.2, to 2.5, to 3.0 AU as the size increases from 51 to 87 to 125 nm.or the largest 125 nm PS NPs, although at diluted concentration,he attenuation due to scattering at 300 nm is AU = 1.2. Thereforehe scattering is providing significant UVB blockage even thoughhe PS has no intrinsic absorbance at this wavelength.
.2. Encapsulation of inorganic filters
Size and morphology of ZnO and TiO2 nanocrystals were deter-ined by TEM measurements. As shown in Fig. 5, ZnO nanospheres
ave an average diameter of 30 nm and TiO2 nanorods have anverage size of 5 nm (diameter) × 40 nm (length). ZnO and TiO2 areurface coated with oleic acid and hexadecylamine, respectively,hus they are hydrophobic and soluble in organic solvent. Fig. 6hows the UV–vis spectra of ZnO and TiO2 solution in THF. Thebsorbance of ZnO and TiO2 solution increases nearly linearly withhe concentration, indicating a similar behavior to molecular fil-
ers; there is a negligible contribution from scattering for particlesn this small size range. This result is consistent with the theoreticaltudy of optimal NP size-wavelength dependence by Popov et al.28].
([PS] = 0.37 mg/mL). For all the three PS NPs, [PS] is the summation of PS homopoly-mer and PS block of the PS-PEG copolymer.
With the FNP technique, PS-b-PEG protected ZnO and TiO2 NPswere prepared with the compositions given in Table S1 in SI. (Thepolymer encapsulated TiO2 NPs at 13% and 20% loading have a meandiameter of 102 and 111 nm, respectively (see Fig. S1b and S1c in SI).
In comparison, stable ZnO NPs were obtained only at low loading(7%) (Fig. S1a in SI). The addition of PS homopolymer as the co-solute does not improve the stability at higher ZnO loading. In the
L. Shi et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 396 (2012) 122– 129 127
Fs
FppipZcbp
3
pNwoTfissb(w
ig. 5. TEM images of nano-sized inorganic filters. (a) spherical ZnO, and (b) rod-hape TiO2.
NP process clusters of the small oxide nanoparticles are incor-orated into a single “composite nanoparticles” (CNP). We havereviously demonstrated this cluster formation for gold colloids
nto CNPs [16]. It seems that the rod shape of TiO2 provides betteracking capability and higher stability for NPs than the sphericalnO. The UV–vis spectra (Fig. S2 in SI) show that the FNP pro-ess creates the larger ∼100 nm CNPs which attenuate UV bothy absorbance and by scattering, giving a dual mechanism of sunrotection.
.3. Co-Encapsulation of organic and inorganic filters
An advantage of the FNP process is the ability to readily incor-orate both organic and inorganic materials in the same compositePs. We demonstrate the flexibility in formulating nanoparticlesith both organic and inorganic actives by formulating a mixture
f A Plus, T 150 and TiO2 nanorods with compositions shown inable 2. The size distributions of the NPs are shown in Fig. 7 with allormulations creating NPs with sizes from 160 to 200 nm. Increas-ng the total actives concentrations (Mix-3 in Table 2) increasedupersaturation and also decreased the loss of A Plus, which was
een previously as the decrease in the absorption peak at � = 355 nmy 20% after dialysis. In the most T 150 concentrated formulationMix-3) the NP dispersion was diluted with an equal volume of DIater after formation so that all the other components (A Plus, TiO2
Fig. 6. (a) UV–vis absorption spectra of surface coated ZnO in THF at various concen-trations, (b) UV–vis absorption vs. [ZnO] at � = 230 nm, (c) UV–vis absorption spectraof surface coated TiO2 in THF at various concentrations, (d) UV–vis absorption vs.[TiO2] at � = 250 nm.
128 L. Shi et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 396 (2012) 122– 129
Table 2Characteristics of composite sunscreen NPs with organic and inorganic NP cores. Loading values are defined with respect to the total solids in the composite nanoparticle.
Sample T 150 loading (wt%) A Plus loading (wt%) TiO2 loading (wt%) Block copolymer loading (wt%) Solids in NP suspension (mg/mL) Mean size (nm) PDI
2.73 174 0.2812.77 162 0.1972.91 186 0.187
aatlNtt�t1iot
Fn
Mix-1 0.0 16.7 16.7 66.7
Mix-2 1.6 16.4 16.4 65.6
Mix-3 6.25 15.6 15.6 62.5
nd PS-PEG) have the same concentrations in the final suspensions in Mix-1 and Mix-2. Note that the UV spectra where on sampleshat were further diluted by the same ratio to obtain data in theinear region of the spectrophotometer. Fig. 8a shows compositePs formulated with A Plus and TiO2. A Plus is most effective in
he UVA wavelengths and the composite NP shows strong absorp-ion for � ∼ 355 nm, but minimal adsorption in the UVB region of
∼ 300 nm. By adding T 150 at 10% wt relative to A Plus the absorp-ion in the UVB region is increased (Mix-2, Fig. 8b). Although T
50 caused precipitations upon storage, the stability was greatly
mproved by increasing the supersaturation during the preparationf Mix-3. Fig. 8c shows that further increasing the T 150 concen-ration such that the final ratio of actives are: T 150/A Plus/TiO2
ig. 7. DLS size distribution and UV–vis absorption spectra of mixture sunscreenanoparticle suspensions. (a) Mix-1, (b) Mix-2 and (c) Mix-3.
and [TiO2] = 0.041 mg/mL), (b) Mix-2, diluted to [Solid] = 0.252 mg/mL ([T150] = 0.004, [A Plus] = 0.041 and [TiO2] = 0.041 mg/mL), and (c) Mix-3, diluted to[Solid] = 0.264 mg/mL ([T 150] = 0.0165, [A Plus] = 0.041 and [TiO2] = 0.041 mg/mL).
of 0.4/1/1, creates strong absorption over the UVA, UVB and UVCwavelengths. The ability to tune the absorption spectra of the NPformulation by FNP provides a powerful tool for preparing moreeffective and safe sunscreen formulations.
4. Conclusions and future directions
We have demonstrated the application of Flash Nanopre-cipitation (FNP) for preparing polymeric NPs as carriers formulticomponent sunscreen agents. In particular, our results showthat FNP is capable of encapsulating both organic and inorganic UV
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L. Shi et al. / Colloids and Surfaces A: Ph
lters, thus offering broad-spectrum UV protection. The size of NPsan be conveniently tuned from 53 nm to 350 nm by varying theoncentrations of core materials and the protecting block copoly-er. The NP formulations of either organic (A Plus or T 150) or
norganic (TiO2 or ZnO) produced stable NPs. The ability to aggre-ate inorganic NPs and to control the size of organic NPs enablesnhanced UV attenuation by both absorption and scattering. Theombination of TiO2, A Plus and T 150 showed the ability to makenanoparticle cocktails” to tune the UV attenuation over the UVA,VB and UVC wavelengths. The composite nanoparticles showedxcellent long-term stability of particle size and UV absorption.
A limitation of current organic UV sunscreens is their relativelyapid transmission through the epidermis [2,29]. Solid NPs are lessusceptible to uptake than emulsions [2]. There are reasons toxpect the loss of active material from our NPs into the skin mighte slower or less than with lipid/surfactant nanoparticle formula-ions that have been previously studied [2]. The large PEG group onhe block copolymer used to stabilize our NPs may be significantlyetter at preventing coalescence between the NP core and the skinhan the much smaller surfactant stabilizers previously used [2],nd the higher glass transition (translating to mechanical stiffness)f our particles has shown greater resistance to small moleculeearrangement than more fluid NP cores [20]. Studies testing thisypothesis would certainly be of interest.
cknowledgements
We would like to thank BASF for continued support and techni-al interactions. In particular we thank Dr. Jack Tinsley of BASF forelpful discussions.
ppendix A. Supplementary data
Supplementary data associated with this article can be found, inhe online version, at doi:10.1016/j.colsurfa.2011.12.053.
[2] S.A. Wissing, R.H. Müller, Solid lipid nanoparticles as carrier for sunscreens:in vitro release and in vivo skin penetration, J. Controlled Release 81 (2002)225–233.
[3] S.A. Wissing, R.H. Müller, The development of an improved carrier system forsunscreen formulations based on crystalline lipid nanoparticles, Int. J. Pharm.242 (2002) 373–375.
[4] E.B. Souto, R.H. Müller, Cosmetic features and applications of lipid nanoparticles(SLN, NLC), Int. J. Cosmet. Sci. 30 (2008) 157–165.
tion tests, and entrapment efficiency studies of carnauba wax-decyl oleatenanoparticles used for the dispersion of inorganic sunscreens in aqueous media,Eur. J. Pharm. Biopharm. 63 (2006) 115–127.
[6] J.R.Villalobos-Hernández, C.C. Müller-Goymann, Sun protection enhancementof titanium dioxide crystals by the use of carnauba wax nanoparticles: the
[
hem. Eng. Aspects 396 (2012) 122– 129 129
synergistic interaction between organic and inorganic sunscreens at nanoscale,Int. J. Pharm. 322 (2006) 161–170.
[7] M. Vettor, P. Perugini, S. Scalia, B. Conti, I. Genta, T. Modena, F. Pavanetto,Poly(d,l-lactide) nanoencapsulation to reduce photoinactivation of a sunscreenagent, Int. J. Cosmet. Sci. 30 (2008) 219–227.
[8] M. Vettor, S. Bourgeois, H. Fessi, J. Pelletier, P. Perugini, F. Pavanetto, M.A.Bolzinger, Skin absorption studies of octyl-methoxycinnamate loaded poly(d,l-lactide) nanoparticles: estimation of the UV filter distribution and releasebehavior in skin layers, J. Microencapsulation 27 (2010) 253–262.
[9] R. Alvarez-Román, B. Barré, H. Fessi, Eur. J. Pharm. Biopharm. 52 (2004)191–195.
tructured lipid carriers (NLC) in cosmetic and dermatological preparations, Adv.Drug Deliv. Rev. 54 (2002) S131–S155.
12] S. Galindo-Rodriguez, E. Allémann, H. Fessi, E. Doelker, Physicochemical param-eters associated with NP formation in the salting-out emulsification-diffusionand nanoprecipitation methods, Pharm. Res. 21 (2004) 1428–1439.
13] B.K. Johnson, R.K. Prud’homme, Chemical processing and micromixing in con-fined impinging jets, AIChE J. 49 (2003) 2264–2282.
14] B.K. Johnson, R.K. Prud’homme, Mechanism for rapid selfassembly of blockcopolymer nanoparticles, Phys. Rev. Lett. 91 (2003) 118302.
15] Y. Liu, C.Y. Cheng, Y. Liu, R.K. Prud’homme, R.O. Fox, Mixing in a multi-inletvortex mixer (MIVM) for flash nanoprecipitation, Chem. Eng. Sci. 63 (2008)2829–2842.
17] T. Chen, S.M. D’Addio, M.T. Kennedy, A. Swietlow, I.G. Kevrekidis, A.Z. Pana-giotopoulos, R.K. Prud’homme, Protected peptide nanoparticles: experimentsand Brownian dynamics simulations of the energetics of assembly, Nano Lett.9 (2009) 2218–2222.
18] M. Akbulut, P. Ginart, M.E. Gindy, C. Theriault, K.H. Chin, W. Soboyejo,R.K. Prud’homme, Generic method of preparing multifunctional fluorescentnanoparticles using flash nanoprecipitation, Adv. Funct. Mater. 19 (2009)718–725.
19] S.J. Budijono, J. Shan, N. Yao, Y. Miura, T. Hoye, R.H. Austin, Y. Ju, R.K.Prud’homme, Synthesis of stable block-copolymer-protected NaYF4:Yb3+, Er3+
cles: aggregation and phase behavior of pyrene and amphotericin B moleculesin nanoparticle cores, Small 6 (2010) 2907–2914.
21] D.H. Adamson, Convenient method for the preparation of poly(ethyleneoxide) and poly(ethylene oxide) block copolymers, Polym. Prepr. 41 (2000)1231–1232.
22] P.D. Cozzoli, A. Kornowski, H. Weller, Colloidal synthesis of organic-cappedZnO nanocrystals via a sequential reduction–oxidation reaction, J. Phys. Chem.B 109 (2005) 2638–2644.
23] J. Joo, S.G. Kwon, T. Yu, M. Cho, J. Lee, J. Yoon, T. Hyeon, Large-scale synthesis ofTiO2 nanorods via nonhydrolytic sol–gel ester elimination reaction and theirapplication to photocatalytic inactivation of E. coli, J. Phys. Chem. B 109 (2005)15297–15302.
24] B.J. Frisken, Revisiting the method of cumulants for the analysis of dynamiclight-scattering data, Appl. Opt. 40 (2001) 4087–4091.
25] BASF Uvinul A Plus brochure.26] U. Hoppe, K. Seib, P. Naegele, R. Martin, S-Triazine derivatives and their use as
sun screen agents, U.S. Patent 4,724,137 (1988).27] Sunscreens, in: M.M. Reiger (Ed.), Harry’s Cosmeticology, Chemical Publishing,
Boston, 2000.28] A.P. Popov, A.V. Priezzhev, J. Lademan, R. Myllylä, Alteration of skin light-
scattering and absorption properties by application of sunscreen nanoparticles:
a Monte Carlo study, J. Quant. Spectrosc. Radiat. Transfer 112 (2011)1891–1897.
29] E. Chatelain, B. Gabard, C. Surber, Skin penetration and sun protection factorof five UV filters: effect of the vehicle, Skin Pharmacol. Appl. Skin Physiol. 16(2003) 28–35.
