Author information: (1)Department of Chemical Engineering, Bldg. E25-342, 45 Carleton St., Cambridge, MA 02139, USA. rlanger@mit.edu

The lipid matrix of the skin's stratum corneum plays a key role in the barrier function, which protects the body from desiccation. The lipids that make up this matrix consist of ceramides, cholesterol, and free fatty acids, and can form two coexisting crystalline lamellar phases: the long periodicity phase (LPP) and the short periodicity phase (SPP). To fully understand the skin barrier function, information on the molecular arrangement of the lipids in the unit cell of these lamellar phases is very desirable. To determine this arrangement in previous studies, we examined the molecular arrangement of the SPP. In this study, neutron diffraction studies were performed to obtain information on the molecular arrangement of the LPP. The diffraction pattern reveals nine diffraction orders attributed to the LPP with a repeating unit of 129.4 ± 0.503. Using D2O/H2O contrast variation, the scattering length density profiles were calculated for protiated samples and samples that included either the perdeuterated acyl chain of the most abundant ceramide or the most abundant perdeuterated fatty acid. Both perdeuterated chains are predominantly located in the central part of the unit cell with substantial interdigitation of the acyl chains in the unit cell center. However, a fraction of the perdeuterated chains is also located near the border of the unit cell with their acyl chains directing toward the center. This arrangement of lipids in the LPP unit cell corresponds with the location of their lipid headgroups at the border and also inside of the unit cell at a well-defined position (±2103 from the unit cell center), indicative of a three-layer lipid arrangement within the 129.4 ± 0.503 repeating unit.

AbstractArbutins (α- and β-arbutins) are glycosylated hydroquinones that are commercially used in the cosmetic industry. These compounds have an inhibitory function against tyrosinase, a critical enzyme for generating pigments, which leads to the prevention of melanin formation, resulting in a whitening effect on the skin. Although β-arbutin is found in various plants including bearberry, wheat, and pear, α-arbutin and other arbutin derivatives are synthesized by chemical and enzymatic methods. This article presents a mini-review of recent studies on the production of α-arbutin and other α- and β-arbutin derivatives via enzymatic bioconversion methods. In addition, the structures of α- and β-arbutin derivatives and their biological activities are discussed. The catalytic characteristics of various enzymes used in the biosynthesis of arbutin derivatives are also reviewed.

This study was designed to develop a skin permeable recombinant low-molecular-weight protamine (LMWP) conjugated epidermal growth factor (EGF) (rLMWP-EGF) by linking a highly positive charged LMWP to the N-terminal of EGF through genetic recombination. We evaluated its biological activity, skin permeability, and wound healing efficacy invivo. The cDNA for rLMWP-EGF was prepared by serial polymerase chain reaction for encoding amino acids of LMWP to the vector for EGF. After expression and purification, recombinant EGF site-specifically conjugated with LMWP was obtained. The invitro cell proliferation activity was well preserved after LMWP conjugation and was comparable to that of rEGF. rLMWP-EGF showed markedly improved permeability through the three-dimensional artificial human skin constructs, and the cumulative permeation of rLMWP-EGF across the excised mouse skin was about 11 times higher than that of rEGF. Topically applied rLMWP-EGF significantly accelerated the wound closure rate in full thickness as well as a diabetic wound model most probably due to its enhanced skin permeation. These findings demonstrate the therapeutic potential of rLMWP-EGF as a new topical wound healing drug and the site-specific conjugation of LMWP to peptides or proteins by genetic recombination as a useful method for preparing highly effective biomedicines.

Phytocompounds have been used in cosmeceuticals for decades and have shown potential for beauty applications, including sunscreen, moisturizing and antiaging, and skin-based therapy. The major concerns in the usage of phyto-based cosmeceuticals are lower penetration and high compound instability of various cosmetic products for sustained and enhanced compound delivery to the beauty-based skin therapy. To overcome these disadvantages, nanosized delivery technologies are currently in use for sustained and enhanced delivery of phyto-derived bioactive compounds in cosmeceutical sectors and products. Nanosizing of phytocompounds enhances the aseptic feel in various cosmeceutical products with sustained delivery and enhanced skin protecting activities. Solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, fullerenes, and carbon nanotubes are some of the emerging nanotechnologies currently in use for their enhanced delivery of phytocompounds in skin care.Aloe vera, curcumin, resveratrol, quercetin, vitamins C and E, genistein, and green tea catechins were successfully nanosized using various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, and hair care for their sustained effects. However, certain delivery agents such as carbon nanotubes need to be studied for their roles in toxicity. This review broadly focuses on the usage of phytocompounds in various cosmeceutical products, nanodelivery technologies used in the delivery of phytocompounds to various cosmeceuticals, and various nanosized phytocompounds used in the development of novel nanocosmeceuticals to enhance skin-based therapy.

In the recent decade, skin delivery (topical and transdermal) has gained an unprecedented popularity, especially due to increased incidences of chronic skin diseases, demand for targeted and patient compliant delivery, and interest in life cycle management strategies among pharmaceutical companies. Literature review of recent publications indicates that among various skin delivery systems, lipid based delivery systems (vesicular carriers and lipid particulate systems) has been the most successful. Vesicular carriers consist of liposomes, ultra-deformable liposomes, and ethosomes while lipid particulate systems consist of lipospheres, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These systems can increase the skin drug transport by improving drug solubilization in the formulation, drug partitioning into the skin and/or fluidizing skin lipids. Considering that lipid based delivery systems are regarded as safe and efficient, they are proving to be an attractive delivery strategy for the pharmaceutical as well as cosmeceutical drug substances. However, development of these delivery systems requires comprehensive understanding of physicochemical characteristics of drug and delivery carriers, formulation and process variables, mechanism of skin delivery, recent technological advancements, specific limitations and regulatory considerations. Therefore, this review article encompasses recent research advances addressing the aforementioned issues.

Solid lipid nanoparticles (SLN) are distinguishable from nanostructured lipid carriers (NLC) by the composition of the solid particle matrix. Both are an alternative carrier system to liposomes and emulsions. This review paper focuses on lipid nanoparticles for dermal application. Production of lipid nanoparticles and final products containing lipid nanoparticles is feasible by well-established production methods. SLN and NLC exhibit many features for dermal application of cosmetics and pharmaceutics, i.e. controlled release of actives, drug targeting, occlusion and associated with it penetration enhancement and increase of skin hydration. Due to the production of lipid nanoparticles from physiological and/or biodegradable lipids, this carrier system exhibits an excellent tolerability. The lipid nanoparticles are a “nanosafe” carrier. Furthermore, an overview of the cosmetic products currently on the market is given and the improvement of the benefit/risk ratio of the topical therapy is shown.

The purpose of this study was to evaluate solid lipid nanoparticles as the topical carrier for epidermal targeting of podophyllotoxin (POD). The high pressure homogenization was employed to prepare drug-loaded solid lipid nanoparticles. The POD-loaded SLN stabilized by 0.5% poloxamer 188 and 1.5% soybean lecithin (P-SLN) and 2% polysorbate 80 (T-SLN) was characterized by photon correlation spectroscopy (PCS). P-SLN showed an average diameter of 73.4 nm and a zeta potential of 61 48.36 mV. The imaging of AFM indicated that the P-SLN had a spherical shape. DSC and X-ray diffraction analysis showed that POD was dispersed in SLN in an amorphous state. The in vitro permeation study showed that P-SLN increased the accumulative amount of POD in porcine skin 3.48 times over 0.15% tincture. But T-SLN with a diameter of 123.1 nm and a zeta potential of 61 17.4 mV did not show a high accumulative amount of POD when compared with P-SLN, though both P-SLN and T-SLN could avoid the systemic uptake of POD. Because of the fluorescence property of POD, fluorescence microscopy imaging was employed to visualize the penetration of POD into skin from SLN. The penetration of POD from P-SLN seemed to follow two pathways along the stratum corneum and hair follicle route. The imaging revealed that P-SLN had a strong localization of POD within epidermis. The penetration of P-SLN with low particle size into stratum corneum along the skin surface ‘furrow’ and the consequent controlled release of POD might lead to the epidermal targeting. P-SLN provides a good epidermal targeting effect and may be a promising carrier for topical delivery of POD.

At the beginning of the nineties solid lipid nanoparticles (SLN) have been introduced as a novel nanoparticulate delivery system produced from solid lipids. Potential problems associated with SLN such as limited drug loading capacity, adjustment of drug release profile and potential drug expulsion during storage are avoided or minimised by the new generation, the nanostructured lipid carriers (NLC). NLC are produced by mixing solid lipids with spatially incompatible lipids leading to special structures of the lipid matrix, i.e. three types of NLC: (I) the imperfect structured type, (II) the structureless type and (III) the multiple type. A special preparation process–applicable to NLC but also SLN–allows the production of highly concentrated particle dispersions (>30–95%). Potential applications as drug delivery system are described.

The aim of this study was to find safer cosmetics for human through application chitin and natural solid lipsomes to sunscreen. Pure chitin is not solved completely in majority chemical agents and traditional chemical UV blockers are potentially harmful to human skin. So the combination of chemical UV absorber and chitin formed 3,4,5-trimethoxybenzoylchitin (TMBC), which was proven as an active chemical sunscreen by Dr. Clausen, and can overcome their inherent defects. Lipophilic ability of the new material can be increased while harmfulness can be decreased due to incorporation natural material chitin. Then solid lipid nanoparticles (SLN) loaded with TMBC to act both as physical sunscreens themselves and as carriers in order to enhance the effect of UVB protection. The improvement of the system can been observed when tocopherol was added.

Liquid crystalline systems of monoolein/water could be a promising approach for the delivery of celecoxib (CXB) to the skin because these systems can sustain drug release, improve drug penetration into the skin layers and minimize side effects. This study evaluated the potential of these systems for the delivery of CXB into the skin based on in vitro drug release and skin permeation studies. The amount of CXB that permeated into and/or was retained in the skin was assayed using an HPLC method. Polarizing light microscopy studies showed that liquid crystalline systems of monoolein/water were formed in the presence of CXB, without any changes in the mesophases. The liquid crystalline systems decreased drug release when compared to control solution. Drug release was independent of the initial water content of the systems and CXB was released from cubic phase systems, irrespective of the initial water content. The systems released the CXB following zero-order release kinetics. In vitro drug permeation studies showed that cubic phase systems allowed drug permeation and retention in the skin layers. Cubic phase systems of monoolein/water may be promising vehicles for the delivery of CXB in/through the skin because it improved CXB skin permeation compared with the control solution.

Abstract The self-assembly of lipids leads to the formation of a rich variety of nano-structures, not only restricted to lipid bilayers, but also encompassing non-lamellar liquid crystalline structures, such as cubic, hexagonal, and sponge phases. These non-lamellar phases have been increasingly recognized as important for living systems, both in terms of providing compartmentalization and as regulators of biological activity. Consequently, they are of great interest for their potential as delivery systems in pharmaceutical, food and cosmetic applications. The compartmentalizing nature of these phases features mono- or bicontinuous networks of both hydrophilic and hydrophobic domains. To utilize these non-lamellar liquid crystalline structures in biomedical devices for analyses and drug delivery, it is crucial to understand how they interact with and respond to different types of interfaces. Such non-lamellar interfacial layers can be used to entrap functional biomolecules that respond to lipid curvature as well as the confinement. It is also important to understand the structural changes of deposited lipid in relation to the corresponding bulk dispersions. They can be controlled by changing the lipid composition or by introducing components that can alter the curvature or by deposition on nano-structured surface, e.g. vertical nano-wire arrays. Progress in the area of liquid crystalline lipid based nanoparticles opens up new possibilities for the preparation of well-defined surface films with well-defined nano-structures. This review will focus on recent progress in the formation of non-lamellar dispersions and their interfacial properties at the solid/liquid and biologically relevant interfaces. Copyright 2014. Published by Elsevier B.V.

The progress on synthesis of colloidal nanocrystals (NCs) has enabled researchers to engineer crystalline nanoparticles over many aspects including composition, size, morphology, crystal structure, surface functionalities, and so on. The rendering unique chemical and physical properties of these precisely engineered colloidal NCs make them superior to their bulk counterparts in many applications, especially for electrochemical reduction reactions that are currently extensively investigated to resolve global energy and environmental issues. Herein we present the recent progress of colloidal NCs and their roles in electrochemical reduction reactions, such as oxygen reduction reaction (ORR), hydrogen evolution reaction (HER), and carbon dioxide reduction reaction (CO2RR). In this feature article, we first introduce the colloidal NCs on the synthesis of colloidal NCs with controlled size, shape, composition and structure. We then focus on the emerging concept in colloidal NCs synthesis, as well as the self-assembly of colloidal NCs to superlattice structures. Afterwards, we discuss the fundamentals and representative strategies in designing colloidal NC structures for superior catalytic performance in ORR, HER and CO2RR. In the end, we provide a perspective on the future opportunities of colloidal NCs in electrochemical reduction reaction applications.

During the past few decades, polymeric micelles have raised special attention as novel nano-sized drug delivery systems for optimizing the treatment and diagnosis of numerous diseases. These nanocarriers exhibit several in vitro and in vivo advantages as well as increased stability and solubility to hydrophobic drugs. An interesting approach for optimizing these properties and overcoming some of their disadvantages is the combination of two or more polymers in order to assemble polymeric mixed micelles. This review article gives an overview on the current state of the art of several mixed micellar formulations as nanocarriers for drugs and imaging probes, evaluating their ongoing status (preclinical or clinical stage), with special emphasis on type of copolymers, physicochemical properties, in vivo progress achieved so far and toxicity profiles. Besides, the present article presents relevant research outcomes about polymeric mixed micelles as better drug delivery systems, when compared to polymeric pristine micelles. The reported data clearly illustrates the promise of these nanovehicles reaching clinical stages in the near future.

This overview follows the evolution of the studies carried out, mainly during last years, on polysaccharide hydrogels, with particular attention on the researches carried out in our department, often in collaboration with other groups in our country and abroad. The review points out the importance of this type of networks for the optimization of drug delivery and targeting in the various forms of macro, micro and nano systems. It is also shown that these materials are suitable for the culture of different types of cells. Release mechanisms are reported and explained by different physico-chemical approaches and by means of molecular dynamics simulations and the anomalous swelling behavior of a scleroglucan/borax hydrogel is thoroughly discussed. The role of polymer combinations forming interpenetrated structures is explained in terms of specific properties which significantly differ from those of the constituent polymers, thus allowing appropriate tailoring of the delivery rates. Finally the wide possibilities of applications of nanogel structures which allow combination therapies for cancer treatment and can be suitable for intracellular targeting are reported. The studies on polysaccharide hydrogels are still in progress and it is underlined that future researches, more focused on the passage from lab to market, should be further stimulated.

A novel transdermal (HA) conjugated with () was developed in the form of solid-in-oil (S/O) nanodispersion (129.7 nm mean diameter). Ex vivo skin penetration analysis by fluorescence and confocal observation of histological skin sections revealed the ability of /HA nanodispersions to cross the stratum corneum and penetrate into the dermis. Furthermore, no significant toxicity was found in fibroblast and keratinocyte in vitro. These results proved the potential of the developed nanodispersion for transdermal delivery of constituting a high value to biopharmaceutical and cosmetics industries.

采用高压匀质技术制备了神经酰胺ⅢB纳米脂质体,平均粒径为71.7 nm,PDI(多分散性系数)为0.214,Zeta电位为-23.3 m V,载药量和包封率分别为2.3%和95.9%。采用Franz扩散池法考察了其体外透皮性能,结果显示,其24 h体外皮肤累积透过量为709.23μg/cm~2,皮肤滞留量为75.07μg/cm~2。相同神经酰胺ⅢB质量分数的纳米脂质体霜剂与普通霜剂相比,前者24 h皮肤滞留量提高了近6倍。比较了连续给药40 d前后小鼠皮肤的水合能力,结果显示,神经酰胺ⅢB纳米脂质体组小鼠皮肤水合能力较对照组有明显提高,小鼠皮肤中总神经酰胺质量浓度高于对照组。

Abstract OBJECTIVES: In the current study, sunscreen and moisturizing properties of solid lipid nanoparticle (SLN)-safranal formulations were evaluated. MATERIALS AND METHODS: Series of SLN were prepared using glyceryl monostearate, Tween 80 and different amounts of safranal by high shear homogenization, and ultrasound and high-pressure homogenization (HPH) methods. SLN formulations were characterized for size, zeta potential, morphology, thermal properties, and encapsulation efficacy. The Sun Protection Factor (SPF) of the products was determined in vitro using transpore tape. The moisturizing activity of the products was also evaluated by corneometer. RESULTS: The SPF of SLN-safranal formulations was increased when the amount of safranal increased. Mean particle size for all formulas was approximately 106 nm by probe sonication and 233 nm using HPH method. The encapsulation efficiency of safranal was around 70% for all SLN-safranal formulations. CONCLUSION: The results conclude that SLN-safranal formulations were found to be effective for topical delivery of safranal and succeeded in providing appropriate sunscreen properties.

Virgin coconut oil (VCO) is the finest grade of coconut oil, rich in phenolic content, antioxidant activity and contains medium chain triglycerides (MCTs). In this work formulation, characterisation and penetration of VCO-solid lipid particles (VCO-SLP) have been studied. VCO-SLP were prepared using ultrasonication of molten stearic acid and VCO in an aqueous solution. The electron microscopy imaging revealed that VCO-SLP were solid and spherical in shape. Ultrasonication was performed at several power intensities which resulted in particle sizes of VCO-SLP ranged from 0.608 ± 0.002 μm to 44.265 ± 1.870 μm. The particle size was directly proportional to the applied power intensity of ultrasonication. The zeta potential values of the particles were from -43.2 ± 0.28 mV to -47.5 ± 0.42 mV showing good stability. The cumulative permeation for the smallest sized VCO-SLP (0.608 μm) was 3.83 ± 0.01 μg/cm2 whereas for larger carriers it was reduced (3.59 ± 0.02 μg/cm2). It is concluded that SLP have the potential to be exploited as a micro/nano scale cosmeceutical carrying vehicle for improved dermal delivery of VCO.

Vitamin E (VE) is highly susceptible to autoxidation; therefore, it requires systems to encapsulate and protect it from autoxidation. In this study, we developed VE delivery systems, which were stabilized by Capsul03 (MS), a starch modified with octenyl succinic anhydride. Influences of interfacial tension, VE viscosity, molecular weight distribution, and surfactant type (MS versus Tween 80) on stability and droplet size obtained by high-pressure homogenization were investigated. Both surfactants reduced interfacial tension and small droplet diameters (<350 nm) were produced at high VE content (80% oil phase, w/w) and low emulsifier (2.5%, w/w), which was attributed to their molecular distribution and interfacial characteristics and the magnitude of disruptive forces generated within homogenizer. MS nanoemulsions were stable to droplet coalescence at high temperature–short time exposure (30, 55, 80°C; 30 min). Results indicated that MS can be used successfully to stabilize VE nanoemulsions at ambient temperatures. Such nanoemulsions may be incorporated in many food products.

Abstract Glabridin, a polyphenolic flavonoid from licorice, has inspired great interest for its antioxidant, anti-inflammatory and skin-lightening activities. However, low water solubility and poor stability of glabridin impedes its topical application in cosmetic products and therapies of dermal diseases. The purpose of this study was to develop a nanosuspension formulation of glabridin to improve its skin permeation. Glabridin nanosuspensions were prepared using anti-solvent precipitation-homogenization method, and Box-Behnken design was adopted to investigate the effects of crucial formulation variables on particle size and to optimize the nanosuspension formulation. The optimal formulation consisted of 0.25% glabridin, 0.47% Poloxamer 188 and 0.11% Polyvinylpyrrolidone K30, and the obtained nanosuspension showed an average particle size of 149.2 nm with a polydispersity index of 0.254. Furthermore, the nanosuspension exhibited significantly enhanced drug permeation flux of glabridin through rat skin with no lag phase both in vitro and in vivo, compared to the coarse suspension and physical mixture. The glabridin nanosuspension showed no significant particle aggregates and a drug loss of 5.46% after storage for 3 months at room temperature. With its enhanced skin penetration, the nanosuspension might be a more preferable formulation for topical administration of poorly soluble glabridin.

Nanoemulsion-based delivery systems can be utilized in functional foods and beverages to improve the bioavailability of nutraceuticals. We determined the influence of carrier oil type on the bioavailability of pterostilbene encapsulated in nanoemulsions containing either flaxseed or olive oil as the carrier oil. The nanoemulsions were then subjected to a simulated gastrointestinal tract (mouth, stomach, small intestine), and the resulting micelle phases were used to establish pterostilbene bioavailability using a Caco-2 cell model. Both nanoemulsions significantly enhanced the bioaccessibility of pterostilbene within the micelle phase. However, olive oil nanoemulsions increased trans-enterocyte transport of pterostilbene more effectively than flaxseed oil ones. Moreover, the patterns of metabolism of pterostilbene during its trans-enterocyte transport were dramatically different when pterostilbene was delivered using nanoemulsions with different carrier oil types.

The aim of this study was to evaluate the skin delivery and in vitro biological activity of trans-resveratrol (RES)-loaded solid lipid nanoparticles (SLNs). The SLNs were composed of stearic acid, poloxamer 407, soy phosphatidylcholine (SPC), an aqueous phase and 0.1% RES. The particle size, polydispersity index (PdI) and zeta potential were analyzed by dynamic light scattering (DLS). The SLNs were analyzed by scanning electron microscopy (SEM-FEG) and differential scanning calorimetry (DSC). In vitro RES-SLN skin permeation/retention assays were conducted, and their tyrosinase inhibitory activity was evaluated. An MTT reduction assay was performed on HaCat keratinocytes to determine in vitro cytotoxicity. The formulations had average diameter lower than 200 nm, the addition of SPC promoted increases in PdI in the RES-SLNs, but decreases PdI in the RES-free SLNs and the formulations exhibited zeta potentials smaller than 3 mV. The DSC analysis of the SLNs showed no endothermic peak attributable to RES. Microscopic analysis suggests that the materials formed had nanometric size distribution. Up to 45% of the RES permeated through the skin after 24 h. The RES-loaded SLNs were more effective than kojic acid at inhibiting tyrosinase and proved to be non-toxic in HaCat keratinocytes. The results suggest that the investigated RES-loaded SLNs have potential use in skin disorder therapies.

Phenylethyl resorcinol (4-(1-phenylethyl)1,3-benzenediol) (PR) is a new whitening agent that has been found to have the ability to inhibit tyrosinase activity. However, the application of PR is limited by photo instability and poor solubility. PR-loaded nanostructured lipid carriers (PR-NLCs) were prepared by the hot-melted ultrasonic method. Glycerol monostearate and olive oil were selected as the solid lipid and liquid lipid for considering the solubility of PR in liquid lipid and partition coefficient of PR in solid lipid, respectively. The particle size and polydispersity index of PR-NLCs were 57.9 ± 1.3 nm and 0.24 ± 0.01, respectively. The encapsulation efficiency and loading capacity of PR-NLCs were 93.1 ± 4.2% and 8.5 ± 0.4%, respectively. The stability test demonstrated that the incorporation of PR into NLCs conferred excellent physicochemical stability and photo stability for at least three months at 4 °C in the dark and 25 °C under daylight. In vitro release of PR-NLCs revealed a sustained release pattern. Cellular tyrosinase assay showed that PR-NLCs could significantly inhibit tyrosinase activity in melanoma cells, suggesting that NLCs can be used as a biocompatible nanocarrier for the effective delivery of skin whitening agents.

The aim of this study was to optimize the preparation method for self-assembled glyceryl monoolein-based cubosomes containing paeonol and to characterize the properties of this transdermal delivery system to improve the drug penetration ability in the skin. In this study, the cubic liquid crystalline nanoparticles loaded with paeonol were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel by high-pressure homogenization. We evaluated the Zeta potential of these promising skin-targeting drug-delivery systems using the Malvern Zeta sizer examination, and various microscopies and differential scanning calorimetry were also used for property investigation. Stimulating studies were evaluated based on the skin irritation reaction score standard and the skin stimulus intensity evaluation standard for paeonol cubosomes when compared with commercial paeonol ointment.In vitrotests were performed on excised rat skins in an improved Franz diffusion apparatus. The amount of paeonol over time in thein vitropenetration and retention experiments both was determined quantitatively by HPLC. Stimulating studies were compared with the commercial ointment which indicated that the paeonol cubic liquid crystalline nanoparticles could reduce the irritation in the skin stimulating test. Thus, based on the attractive characteristics of the cubic crystal system of paeonol, we will further exploit the cosmetic features in the future studies. The transdermal delivery system of paeonol with low-irritation based on the self-assembled cubic liquid crystalline nanoparticles prepared in this study might be a promising system of good tropical preparation for skin application.

Astaxanthin is a naturally occurring carotenoid with strong antioxidant properties which shows low oral bioavailability due to its lipophilicity. The use of nanoemulsion-based formulations is one of several approaches found to be efficient in improving the bioavailability of lipophilic entities such as astaxanthin. This study explores the effects of various emulsifying conditions on the physicochemical properties and stability evaluation of astaxanthin nanoemulsion in order to optimize its production method. Astaxanthin nanoemulsion prepared in various emulsifying conditions was evaluated for its effects on the physicochemical characteristics and stability for a period of 3 months. The optimal formulation obtained required 5 minutes and 9000 rpm pre-homogenizing speed, high pressure (800 bar) and 5 cycles with composition of 4% surfactant, 16% oil and 80% water. Astaxanthin loaded in the optimal formulation were stable after the manufacturing process and storage at 5±3°C, 25±2°C/60±5% Relative humidity (RH) and 40°C±2°C/75%±5% RH for 3 months. The findings of this study will lead to the possibility of this formulation to be used as one of the method to improve astaxanthin bioavailability.

Proanthocyanidin liposome modified by polyethylene glycol (PEG) was prepared by reverse-phase evaporation method. To obtain the higher encapsulation efficiency of proanthocyanidin liposomes, several factors, including the mass ratio of lecithin to cholesterol and the addition of surfactants and PEG, were investigated. The liposomes then can be evaluated by encapsulation efficiency, the distribution of particle size and storage stability. The results showed that the encapsulation efficiency of the liposomes was around 77.2802%, and the average particle size of the liposomes was 144.902±020.102nm. In addition, proanthocyanidin could be controlled to release on simulated skin in vitro. These data confirmed that the liposomes could be employed to extend proanthocyanidin’s shelf life and to provide more convenience and better performance for its usage in cosmetics.

SynopsisObjectiveTocopherol is stronger antioxidant than tocopherol acetate but due to its viscous form, poor water solubility, instability to light and skin irritation issues it is not used in the current marketed formulations. To overcome the drawbacks, tocopherol was formulated as nanostructured lipid carriers and nanoemulsion. The objective of the study was to formulate tocopherol as nanocarriers.MethodNanostructured lipid carriers (NLCs) and nanoemulsion (NE) were prepared by homogenization technique. They were characterized for particle size and zeta potential. In vitro release study was performed using dialysis method, and skin permeation was carried out using human cadaver skin. Further, antioxidant activity was tested by ferric reducing antioxidant potential (FRAP) assay and skin irritation testing was performed on Epiderm skin model. Effect of UV degradation was studied using solar simulator.ResultsThe size and zeta potential of NLC was 67.002nm02±021.2 and 6132.002mV02±021.2, whereas for NE, it was 586.502nm02±02209.6 and 611002mV02±020.6. In vitro release study showed that 30% of tocopherol was released from NLC in the first 202h of the study as compared to only 4% from NE. Permeation study from human skin showed that 762.302ng02mL61102±02184.6 of tocopherol was delivered into the epidermis when formulated as NLCs as compared to 182.3 ng02mL61102±0252.7 from NE. FRAP assay was performed to test the antioxidant activity of formulated tocopherol, and it was seen that both formulations were able to retain the antioxidant activity. Skin irritation testing showed that NLC was non-irritant to the skin. NLC and NE were also able to protect tocopherol from UV degradation.ConclusionBased on the studies conducted, it can be concluded that formulating tocopherol as NLCs is beneficial to produce a stable, non-irritant and aqueous formulation.RésuméObjectifLe Tocophérol est un antioxydant plus fort que le tocophérol acétate, mais en raison de sa forme visqueuse, sa faible solubilité dans l' eau, son instabilité envers la lumière et des questions d'irritation de la peau, il n'est pas utilisé dans les formulations actuellement commercialisées. Pour surmonter les inconvénients, le tocopherol a été formulé en tant dans des lipides nanostructurés et sous forme de nanoémulsion. L'objectif de l'étude était de formuler le tocophérol comme des nanovecteurs .MéthodeLes transporteurs lipidiques nanostructurés (TLN) et nanoémulsion (NE) ont été préparés par la technique d'homogénéisation. Ils ont été caractérisés pour la taille des particules et le potentiel zêta. L'étude in vitro de la libération a été effectuée en utilisant la méthode de dialyse et la perméation de la peau a été réalisée en utilisant la peau de cadavre humain. En outre, l'activité antioxydante a été testée par le potentiel de réduction ferrique antioxidante (FRAP) et l'irritation de la peau a été réalisée sur le modèle de la peau Epiderm. L'effet de la dégradation par les UV a été étudié en utilisant un simulateur solaire.RésultatsLa taille et le potentiel zêta du TLN était de 67,0 ± 1,2 nm et -32,0 mV ± 1.2 alors que pour NE c'était 586.5 nm ± 209.6 et -10 mV ± 0,6. L'étude de libération in vitro a montré que 30% de tocophérol a été libéré du TLN dans les deux premières heures de l'étude, comparativement à seulement 4% de NE. L'étude de perméation de la peau humaine a montré que 762,3 ng / mL ± 184,6 de tocophérol ont été livré dans l'épiderme lorsqu'ils sont formulés comme TLN comparativement à 182,3 ng / mL ± 52,7 de NE. Le dosage de la FRAP a été effectuée pour tester l' activité anti-oxydante des tocophérols formulés et on a vu que les deux formulations ont été capables de maintenir l'activité antioxydante. Le test d'irritation cutanée a montré que le TLN était non irritant pour la peau. TLN et NE ont également été en mesure de protéger le tocophérol de la dégradation par des UV .ConclusionSur la base des études réalisées, on peut conclure que la formulation de tocophérol comme sous forme de TLN est bénéfique pour produire une formulation stable, non irritant et aqueuse.

目的:研制辅酶Q10纳米结构脂质载体(Q10-NLC),并对其皮肤靶向性进行评价。方法:采用高压微射流技术制备Q10-NLC,运用响应面设计优化处方,并对其理化性能、稳定性及体外释放行为进行表征;采用Franze扩散池法评价Q10-NLC体外透皮性能。结果:通过响应面设计得到Q10-NLC优化处方,按照优化处方制备的Q10-NLC粒径为151.7 nm,多分散指数(PDI)0.144,Zeta电位-44.1 mV,载药量2.51%,包封率100%;24 h光照后,Q10-NLC中Q10含量下降5.59%,显著低于乳剂和乙醇溶液中Q10的光解量;体外药物释放表明,Q10-NLC具有明显的缓释行为;体外透皮吸收实验结果显示,Q10-NLC的药物皮肤滞留量为Q10乳剂的10.11倍。结论:Q10-NLC可有效提高Q10的稳定性,延长其作用时间,实现Q10皮肤靶向给药。

Objective: The objective of this work was to prepare coenzyme Q10 loaded nanostructured lipid carriers (Q10-NLC) and evaluate its epidermal targeting effect.Methods: Q10-NLC was prepared by high-pressure microfluidics technique. Formulations and preparation parameters were optimized with response surface design. Q10-NLC was characterized by PCS, TEM, DSC and PXRD. The penetration of Q10 from the Q10-NLC formulations through skins and into skins were evaluated in vitro using Franz diffusion cells fitted with SD rat skins. In vitro release, long-term stability and light stability were also evaluated.Results: The results showed that the concentration of solid lipid and emulsifier in formulation had a significant influence on particle size. The optimized preparation parameters were magnetic stirring for 20 min, high stirring at 8000 rpm for 1 min and high-pressure microfluidics at 1200 bar for three cycles. The size of Q10-NLC prepared by optimized formulation and parameters was (151.7 +/- 2.31) nm, polydispersity (PDI) 0.144, zeta potential was (-44.1 +/- 1.68) mV, drug loading 2.51%, encapsulation efficiency 100%. In vitro release study, Q10-NLC showed fast release during the first 3 hours and prolonged release afterwards. In vitro skin permeation study, the accumulative uptake of Q10 in epidermal of Q10-NLC was 10.11 times over Q10 emulsion. After exposure to day light for 24 hours, the amount of Q10 in Q10-NLC decreased only 5.59%, while in Q10 emulsion decreased 24.61% and Q10-ethanol solution 49.74%.Conclusion: Q10-NLC exhibited a significant epidermal targeting effect, which was proved to be a promising carrier for topical delivery of Q10.

Polar compounds with large molecular weight have poor membrane permeability, liposomes can promote drugs to penetrate epidermis and remain or release at dermis. Madecassoside (MA) exhibits powerful potency in treatment of skin disorders such as wound healing, scar management, and psoriasis, but it is not easy to penetrate epidermis for its hydrophilic nature. The aim of this work is to get the optimum process conditions and evaluate physicochemical properties and physical stability of MA liposomes. In order to avoid this disadvantage and maintain long term drug storage, MA Liposomes were designed to achieve optimum preparation conditions using response surface methodology (RSM) in our experiment. The process and formulation variables were optimized by achieving maximum drug encapsulation efficiency. The optimum conditions were 0.4424g of madecassoside, 8.174 of ratio of egg yolk lecithin to cholesterol, 65s of ultrasonic time. The results of particle size, zeta potential and encapsulation efficiency of madecassoside liposomes were 293nm, 35.6mV, and 40.90%, respectively, on the basis of the above optimum conditions. According to the morphology of liposomes and encapsulation efficiency of triplicate experiments conducted at optimum conditions, MA liposomes obtained by this optimized formulation had characters of favorable repeatability and proper particle size. The physical stability tests of MA liposomes indicated that its suitable storage temperature was at 4 C with higher encapsulation efficiency.

ALA-loaded nanostructured lipid carrier (ALA-NLC) was designed to improve physicochemical stability and water solubility, and promote sustained release of ALA as well as determine the biocompatibility of ALA-NLC. The ALA-NLC manufactured using hot high-pressure homogenization technique was investigated in terms of size, zeta potential, FTIR analysis and release behavior. In vitro cytotoxicity and biocompatibility were determined by incubating with HaCaT cells using the MTT assay, HE staining and Hoechst 33342 staining. Cell behavior and cellular division of HaCaT cells untreated and treated by ALA-NLC were investigated in real-time images gathered using time-lapse imaging system. The release investigation illustrated that only 6.9% of ALA released in 30 min from ALA-NLC formation, whereas it was 30.3% in free ALA system. ALA-NLC possessed a satisfactory release behavior of sustained release up to 72 h. It showed that ALA-NLC did not exert hazardous effect on HaCaT cells up to 81.9 mg/L without morphological alterations, revealing a satisfactory biocompatibility. Evidence was provided from time-lapse imaging system that cell behavior and cellular division of ALA-NLC treated HaCaT cells were in accordance with the control. These results of this investigation demonstrated that NLC encapsulated ALA formation (ALA-NLC) can improve stability, solubility and release of ALA; ALA-NLC was biocompatible to HaCaT cells.

Pomegranate peel and seeds have demonstrated to possess antioxidant compounds with potential application to protect the skin against the ultraviolet radiation damage. However, the photoprotection acti

Abstract The main objective of this study was to evaluate the potential of quercetin-loaded nanostructured lipid carriers (QT-NLCs) as a topical delivery system. QT-NLCs were prepared by the method of emulsion evaporation-solidification at low temperature. The average entrapment efficiency and drug loading of the optimized QT-NLCs were 89.95 ± 0.16% and 3.05 ± 0.01%, respectively. Under the transmission electron microscope, the nanoparticles were spherically shaped. The average particle size was 215.2 nm, the zeta potential was -20.10 ± 1.22 mV and pH value of QT-NLCs system was 4.65. Topical delivery of QT in the form of NLCs was investigated in vitro and in vivo. The results showed that QT-NLCs could promote the permeation of QT, increase the amount of QT retention in epidermis and dermis, and enhance the effect of anti-oxidation and anti-inflammation exerted by QT. Then the mechanism of NLCs for facilitating drug penetration was further investigated through histological sections. In conclusion, NLCs could be a promising vehicle for topical delivery of QT. Copyright 08 2012 Elsevier B.V. All rights reserved.

Background The use of natural products based on aqueous extract of propolis and lycopene in the skin's protective mechanisms against UVA radiation was evaluated by means of experimental acute inflammation on rat paw edema. The aim of the present study was to evaluate the harmlessness of propolis - lycopene system through evaluation of skin level changes and anti-inflammatory action. The regenerative and protective effect of the aqueous propolis and lycopene extract is based on its richness in biologically active substances such as: tocopherols, flavonoids, amino acids, polyunsaturated fatty acids, the chlorophyll pigment, all substances with strong antioxidant activity, that modify the oxidative stress, mainly by reducing the prooxidant processes and enhancing the antioxidant ones. These substances participate in the synthesis of prostaglandins and phospholipids components of cell membrane thus enhancing skin protection mechanisms. Results The experimental systems offered a sustained release of the drug, in vitro , for aim eight hours. The prepared formulations aim did not reveal a deteriorating effect on tissues. They proved a better therapeutic efficiency Compared to standard suspension, they provided a better therapeutic efficiency coupled with extended time interval of tested parameters (24 hours). Preliminary examination of tissues showed that the experimental formulations did not irritate. Local application of propolis and lycopene aqueous extract nanoemulsion has a high potential both regarding its efficiency (the analgesic effect) and therapeutic safety. Conclusions This study demonstrates that propolis and lycopene extract nanoemulsions, preparations contains active substances, can confer better therapeutic effects than those of the conventional formulations, based on local control-release of dozed form, for a longer period of time, which probably improve its efficiency and skin acceptance, meaning a better compliance. The information obtained in the present study suggests that administration of propolis and lycopene aqueous extract nanoemulsion is safe. The preparation can be useful for further preclinical studies lycopene embedded in aqueous propolis extract to be used in pharmaceuticals (targeted medical therapy).

Lutein is a well known antioxidant and anti-free radical used in cosmetic, nutraceutical industry with potential application in pharmaceutics as supportive antioxidant in treatments. As lipophilic molecule it is poorly soluble in water and has a low bioavailability. Lutein nanosuspension was prepared to enhance dissolution velocity, saturation solubility ( C s ), which are major factors determining oral bioavailability and penetration into the skin. High pressure homogenization (HPH) was used to prepare lutein nanosuspension. Particle size was determined by photon correlation spectroscopy (PCS) and laser diffractometry (LD). The lowest PCS diameter obtained was about 42902nm, the LD diameter 90% of 1.202μm. The zeta potential was about 614002mV in water and 611702mV in the original dispersion medium. The 3 month storage study at different temperatures (402°C, 2502°C, 4002°C) confirmed physical stability despite the low zeta potential of 611702mV in original surfactant solution. A pronounced increase in saturation solubility by 26.3 fold was obtained for lutein nanocrystals compared to coarse powder. The lutein nanosuspension was converted into pellets and filled into hard gelatin capsules for nutraceutical use, showed a superior in vitro release (factor of 3–4). Lyophilized nanosuspension was prepared for subsequent incorporation into creams and gels. The lyophilized nanosuspension was very well re-dispersible (43502nm). Using cellulose nitrate membranes as in vitro model, permeation through this barrier was 14× higher for lutein nanocrystals compared to coarse powder. However, pig ear skin did not allow lutein to permeate but supported localization of the lutein in the skin where it should act anti-oxidatively.

Abstract The aim of this study was to evaluate the efficacy of Thai basil oils and their micro-emulsions, on in vitro activity against Propionibacterium acnes. An agar disc diffusion method was employed for screening antimicrobial activity of the essential oils of Ocimum basilicum L. (sweet basil), Ocimum sanctum L. (holy basil) and Ocimum americanum L. (hoary basil) against P. acnes. Minimum inhibitory concentration (MIC) values of the basil oils were determined using an agar dilution assay. The obtained results indicated that the MIC values of sweet basil and holy basil oils were 2.0% and 3.0% v/v, respectively, whereas hoary basil oil did not show activity against P. acnes at the highest concentration tested (5.0% v/v). Gas chromatography-mass spectrometry analysis revealed that methyl chavicol (93.0%) was the major compound in sweet basil oil, and eugenol (41.5%), gamma-caryophyllene (23.7%) and methyl eugenol (11.8%) were major compounds in holy basil oil. Hoary basil oil contained high amounts of geraniol (32.0%) and neral (27.2%) and small amounts of methyl chavicol (0.8%). The Oil-in-water (o/w) micro-emulsions of individual basil oils with concentrations corresponding to their MIC values were formulated. The stable o/w micro-emulsion system for basil oil consisted of 55.0% v/v water phase, 10.0% v/v oil phase (2.0 or 3.0% v/v sweet basil or 3.0% v/v holy basil oil plus 7.0% v/v isopropyl myristate), 29.2% v/v polysorbate 80 and 5.8% v/v 1,2-propylene glycol. Hydroxyethylcellulose at a concentration of 0.5% w/v was used as thickening agent. According to the disc diffusion assay, the formulations containing sweet basil oil exhibited higher activity against P. acnes than those containing holy basil oil, and the thickened formulations tended to give a lower activity against P. acnes than the non-thickened formulations. The prepared micro-emulsions were stable after being tested by a heat-cool cycling method for five cycles. These findings indicate the possibility to use Thai sweet and holy basil oil in suitable formulations for acne skin care.

为研制丹参酮Ⅱ_A纳米结构脂质载体(Tan Ⅱ_A-NLC),并进行体外透皮研究。该文采用高压均质技术制备Tan Ⅱ_ANLC,运用Box-Behnken设计-效应面法优化处方,并对其进行表征。采用Franze扩散池法评价Tan Ⅱ_A-NLC体外透皮性能。结果显示,以最优处方:脂药比为88、固液脂质比为2、稳定剂用量为1%,制得的Tan Ⅱ_A-NLC粒径为(182±14)nm,多分散指数(PDI)为0.190 6±0.024 5,Zeta电位(-27.8±5.4)m V,包封率(EE)为86.44%±9.26%,载药量(DL)为0.98%±0.18%;体外透皮吸收实验结果显示Tan Ⅱ_A-NLC的24 h药物累积透皮量低于溶液,但其在表皮中的滞留量是溶液的3.18倍。TanⅡ_A-NLC可有效提高Tan Ⅱ_A在表皮层的滞留量,具有广阔的应用前景。

黄芩苷具有多种药理活性,但其在脂水中的溶解度限制了临床应用。本文通过查阅目前利用新技术和新剂型增加黄芩苷溶解度,改善黄芩苷的生物利用度的研究文献,从环糊精包合物、固体分散体、磷脂复合物、微粒给药系统、金属配合物、明胶微球、透皮制剂等方面进行了综述,提出发展前景,为黄芩苷的进一步研究开发提供参考。

The purpose of the present research was to develop Silybin loaded solid lipid nanoparticle gel (SIL-SLN gel) for irritant contact dermatitis (ICD). ICD is associated with reduced skin water content, emerging in dry skin condition and relapsing eczema. SIL is a naturally occurring flavones, which shows antioxidant activity and helps in the treatment of ICD. In this study, the SLN was prepared by the ultrasonic probe sonication method and further evaluated for particle size and entrapment efficiency. Results of optimized batch showed mean particle size 1390.35nm and entrapment efficiency 90.970.91%. Optimized batch was freeze dried and characterized by field emission scanning electron microscopy (FE-SEM), it shows particles are in nano range, with spherical morphology and smooth surface. Finally, the SLN was incorporated into gel for convenient topical application. The SIL-SLN-gel were evaluated for in-vitro skin occlusivity, skin irritation and ex-vivo diffusion and deposition study and further compared with SIL-plain gel. Efficacy of gel on dinitrochlorobenzene (DNCB) induced ICD mice were evaluated by skin water content, ear swelling and histopathology. Ex-vivo study of SIL-SLN gel exhibited prolonged drug release, whereas the skin irritation study shows no irritancy. In DNCB induced ICD mice SIL-SLN gel showed higher efficacy than SIL-plain gel.

Abstract The acne skin is characteristic of a relatively lower pH microenvironment compared to the healthy skin. The aim of this work was to utilize such pH discrepancy as a site-specific trigger for on-demand topical adapalene delivery. The anti-acne agent, adapalene, was encapsulated in acid-responsive polymer (Eudragit03 EPO) nanocarriers via nanoprecipitation. The nanocarriers were characterized in terms of particle size, surface morphology, drug-carrier interaction, drug release and permeation. Adapalene experienced a rapid release at pH 4.0 in contrast to that at pH 5.0 and 6.0. The permeation study using silicone membrane revealed a significant higher drug flux from the nanocarrier (6.5 ± 0.6 μg.cm(-2).h(-1)) in comparison to that (3.9 ± 0.4 μg.cm(-2).h(-1)) in the control vehicle (Transcutol03). The in vitro pig skin tape stripping study showed that at 24 h post dose-application the nanocarrier delivered the same amount of drug to the stratum corneum as the positive control vehicle did. The acid-responsive nanocarriers hold promise for efficient adapalene delivery and thus improved acne therapy.

The present work reports on microcapsulation of salicylic acid by spray drying using maltodextrin (MD), gum Arabic (GA), and encapsulation behavior confirmed by FT-IR and SEM. The optimum GA/MD ratio, solubility, release mechanism and in-vitro transdermal study were evaluated. The results revealed the optimum ratio of 1:1 and an improved water solubility of 26mg/mL. SA microcapsules presented sphere-like structure and a slower release rate than pure SA. In-vitro transdermal results showed that SA microcapsules presented a lower permeability rate within 19hours with no sudden permeability. Furthermore, SA microcapsules presented higher SA retention on skin surface and lower skin retention.

Although entrapment of nanoparticles of appropriate sizes at hair follicles has been clarified, there is no report on specific clinical application of this finding. Since sebaceous gland is associated with hair follicle, we hypothesize that effective acne vulgaris treatment/prevention can be achieved by depositing anti-acne agent in nanoparticle form at the hair follicles. Challenge of this strategy, however, lies at the finding of effective anti-acne particles with minimal skin irritation. Here using cellulose-based nanoparticles as nano-reservoir and -mangostin (an active component isolated from the edibleGarcinia mangostanaLinn. fruit) as anti-acne agent, we prepare nanoparticles highly loaded with -mangostin. Ability of the obtained particles to sustained release -mangostin into synthetic sebum is demonstrated. The obtained mangostin particles are verified for their insignificant skin irritation through the two-week, twice-daily open application test in 20 healthy human volunteers. Excellent entrapment and sustainment of the mangostin nanoparticles at the hair follicles are elucidated in six human volunteers by detecting the presence of -mangostin at the roots of hairs pulled from the treated skin area. The 4-week-randomized, double-blind, placebo-controlled, split-face study in 10 acne patients indicates significant improvement in acne vulgaris condition on the side twice daily applied with mangostin nanoparticles.

Solid lipid nanoparticles have been reported as possible carrier for skin drug delivery. Solid lipid nanoparticles are produced from biocompatible and biodegradable lipids. Solid lipid nanoparticles made of semi-synthetic triglycerides stabilized with a mixture of polysorbate and sorbitan oleate were loaded with 5% of minoxidil. The prepared systems were characterized for particle size, pH and drug content. Ex vivo skin penetration studies were performed using Franz-type glass diffusion cells and pig ear skin. Ex vivo skin corrosion studies were realized with a method derived from the Corrositex 庐 test. Solid lipid nanoparticles suspensions were compared to commercial solutions in terms of skin penetration and skin corrosion. Solid lipid nanoparticles suspensions have been shown as efficient as commercial solutions for skin penetration; and were non-corrosive while commercial solutions presented a corrosive potential. Solid lipid nanoparticles suspensions would constitute a promising formulation for hair loss treatment.

Abstract Top of page Abstract Introduction Materials and Methods Results and Discussions Conclusions Acknowledgments References The coencapsulation of two UV filters, butyl-methoxydibenzoylmethane (BMDBM) and octocrylene (OCT), into lipid nanocarriers was explored to develop stable cosmetic formulations with broad-spectrum photoprotection and slow release properties. Different types of nanocarriers in various concentrations of the two UV filters were tested to find the combination with the best absorption and release properties. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been the two types of lipid nanocarriers used. The NLCs were based on either medium chain triglycerides (MCT) or squalene (Sq). The following physicochemical properties of the nanocarriers have been evaluated: particle size, morphology, zeta potential (ZP), entrapment efficiency, loading capacity, and thermal behavior. The nanocarriers have been formulated into creams containing low amounts of UV filters (2.5% BMDBM and 1% OCT). The best photoprotection results were obtained with the cream based on NLCs prepared with MCT, having a sun protection factor (SPF) of 17.2 and an erythemal UVA protection factor (EUVAF) of 50.8. The photostability of the encapsulated BMDBM filter was confirmed by subjecting the nanocarriers-based creams to in vitro irradiation. The prolonged UV-protection efficacy was coupled with a slow in vitro release of the synthetic UV filters, which followed the Higuchi release model.