Lipid nanoparticles as carrier for octyl-methoxycinnamate: in vitro percutaneous absorption and photostability studies

The aim of the present study was the evaluation of lipid nanoparticles (solid lipid nanoparticles, SLN, and nanostructured lipid carriers, NLC) as potential carriers for octyl-methoxycinnamate (OMC). The release pattern of OMC from SLN and NLC was evaluated in vitro, determining its percutaneous absorption through excised human skin. Additional in vitro studies were performed in order to evaluate, after UVA radiation treatment, the spectral stability of OMC-loaded lipid nanoparticles. From the obtained results, ultrasonication method yielded both SLN and NLC in the nanometer range with a high active loading and a particle shape close to spherical. Differential scanning calorimetry data pointed out the key role of the inner oil phase of NLC in stabilizing the particle architecture and in increasing the solubility of OMC as compared with SLN. In vitro results showed that OMC, when incorporated in viscosized NLC dispersions (OMC-NLC), exhibited a lower flux with respect to viscosized SLN dispersions (OMC-SLN) and two reference formulations: a microemulsion (OMC-ME) and a hydroalcoholic gel (OMC-GEL). Photostability studies revealed that viscosized NLC dispersions were the most efficient at preserving OMC from ultraviolet-mediated photodegradation.     

Solid lipid nanoparticles (SLNTM/LipopearlsTM) a pharmaceutical and cosmetic carrier for the application of vitamin E in dermal products

Solid lipid nanoparticles (SLNTM, LipopearlsTM) are nanoparticles made from solid lipids by highpressurehomogenization. Incorporation of chemically labile active ingredients intothe solid lipid matrix protects against chemical degradation, which is shown for vitamin E. The SLN are physically stable in aqueous dispersions and also after incorporation into a dermal cream as proven by photon correlation spectroscopy and differential scanning calorimetry. Electron microscopy and atomic force microscopy data reveal the spherical shape of the SLN and the detailed structure of the particle surface. Ultrafine particles form an adhesive film leading to an occlusive effect on the skin. The occlusion promotes the penetration of vitamin E into the skin, as shown by the stripping test. In addition to chemical stabilization of active ingredients, occlusive effects on the skin and subsequent enhanced penetration of compounds, the SLN also possess a pigment effect covering undesired colours leading to an increased aesthetic acceptance by the customer.     

Solid lipid nanoparticles (SLN/Lipopearls)--a pharmaceutical and cosmetic carrier for the application of vitamin E in dermal products

Solid lipid nanoparticles (SLN, Lipopearls) are nanoparticles made from solid lipids by high pressure homogenization. Incorporation of chemically labile active ingredients into the solid lipid matrix protects against chemical degradation, which is shown for vitamin E. The SLN are physically stable in aqueous dispersions and also after incorporation into a dermal cream as proven by photon correlation spectroscopy and differential scanning calorimetry. Electron microscopy and atomic force microscopy data reveal the spherical shape of the SLN and the detailed structure of the particle surface. Ultrafine particles form an adhesive film leading to an occlusive effect on the skin. The occlusion promotes the penetration of vitamin E into the skin, as shown by the stripping test. In addition to chemical stabilization of active ingredients, occlusive effects on the skin and subsequent enhanced penetration of compounds, the SLN also possess a pigment effect covering undesired colours leading to an increased aesthetic acceptance by the customer.     

Cosmetic applications for solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) are novel delivery systems for pharmaceutical and cosmetic active ingredients. This paper highlights advantages of SLN for cosmetic applications. The dependence of the occlusive effect on the particle size of SLN due to film formation is presented by in vitro data. An in vivo study showed that addition of 4% SLN to a conventional o/w cream lead to an increase of skin hydration of 31% after 4 weeks. The application of SLN as physical sunscreens and as active carriers for molecular sunscreens has also been investigated. The amount of molecular sunscreen could be decreased by 50% while maintaining the protection level compared to a conventional emulsion.     

Percutaneous absorption of flavan-3-ol conjugates from plant procyanidins

Catechins (flavanols) are strong antioxidants, free radical scavengers and inhibitors of lipid peroxidation. New bio-based antioxidant compounds obtained by depolymerization of plant polymeric flavanols (procyanidins) in the presence of cysteine or cysteamine, as well as their underivatized counterpart, (-)-epicatechin, were evaluated in terms of their percutaneous absorption profiles taking into account their free radical scavenging efficiency. The evaluation of the percutaneous absorption of flavanols was carried out by an in vitro methodology using both pig and human skin. A good correlation was obtained using both skins in the evaluation of the skin absorption profiles. It can be deduced that 4beta-(S-cysteinyl)epicatechin (Cys-Ec) has a tendency to be located mainly in the outermost layers of the skin, whereas 4beta-(2-aminoethylthio)epicatechin (Cya-Ec) has a pronounced percutaneous absorption capacity. Their antioxidant properties and their skin penetration profiles support their potential cosmetic or pharmacological applications.     

New insights into the mucoadhesion of pectins by AFM roughness parameters in combination with SPR

The high content of surfactants is one of the major limits to microemulsions (MEs) use in pharmaceutical and cosmetic field. In this work MEs with low surfactant content were prepared by the phase inversion temperature (PIT) method using different oil phases and emulsifiers. The effects of vehicle composition on in vitro release and skin permeation of octylmethoxycinnamte (OMC), one of the most used UVB filter, was evaluated. These MEs showed droplet sizes in the range 32-77nm and a single peak in size distribution. MEs prepared using the most lipophilic lipids (decyl oleate or cetyl stearyl isononanoate) showed the lowest stability. In vitro release and skin permeation profiles were affected by both lipophilicty and structure of the lipid used as internal phase and the formulation that released the lowest amount of OMC provided the lowest active compound skin permeation. It is noteworthy that no OMC release and skin permeation were observed using oleth-20/glyceryl oleate as emulsifiers. Furthermore, a skin permeation enhancement effect was observed depending on the vehicle components. The results of this work suggest that PIT MEs could provide controlled skin drug delivery by choosing proper associations of oil phase lipids and emulsifiers.     

Lipid nanocarriers for dermal delivery of lutein: preparation, characterization, stability and performance

Topical application of lutein as an innovative antioxidant, anti-stress and blue light filter, which is able to protect skin from photo damage, has got a special cosmetic and pharmaceutical interest in the last decade. Lutein is poorly soluble, and was therefore incorporated into nanocarriers for dermal delivery: solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and a nanoemulsion (NE). Nanocarriers were produced by high pressure homogenization. The mean particle size was in the range of about 150 nm to maximum 350 nm, it decreased with increasing oil content of the carriers. The zeta potential in water was in the range -40 to -63 mV, being in agreement with the good short term stability at room temperature monitored for one month. In vitro release was studied using a membrane free model. Highest release in 24h was observed for the nanoemulsion (19.5%), lowest release (0.4%) for the SLN. Release profiles were biphasic (lipid nanoparticles) or triphasic (NE). In vitro penetration study with a cellulose membrane showed in agreement highest values for the NE (60% in 24h), distinctly lower values for the solid nanocarriers SLN and NLC (8-19%), lowest values for lutein powder (5%). Permeation studies with fresh pig ear skin showed that no (SLN, NLC) or very little lutein (0.4% after 24h) permeated, that means the active remains in the skin and is not systemically absorbed. The nanocarriers were able to protect lutein against UV degradation. In SLN, only 0.06% degradation was observed after irradiation with 10 MED (Minimal Erythema Dose), in NLC 6-8%, compared to 14% in the NE, and to 50% as lutein powder suspended in corn oil. Based on size, stability and release/permeation data, and considering the chemical protection of the lutein prior to its absorption into the skin, the lipid nanoparticles are potential dermal nanocarriers for lutein.     

刺山柑果凝胶膏剂的体外透皮研究

目的研究不同促透剂对刺山柑果凝胶膏中有效成分体外透皮吸收的影响,筛选有效的促透剂。方法选择不同质量分数的氮酮、丙二醇以及氮酮与丙二醇的不同质量比例组合物为促透剂,采用改良的Franz扩散池,以离体小鼠皮肤为透皮屏障,用HPLC测定接收液中有效成分芦丁的含量,考察不同促透剂对刺山柑果凝胶膏中芦丁的单位面积累积透过量和透皮速率常数的影响。结果 20mg.g-1氮酮促渗效果较好,其促渗倍数为1.26倍,芦丁的透皮速率常数为5.45μg.cm-2.h-1。结论不同促透剂对刺山柑果凝胶膏中有效成分的透皮吸收的影响有差异,其中20mg.g-1氮酮能够有效促进凝胶膏中芦丁的体外透皮吸收,可作为刺山柑果凝胶膏的促透剂。     

Nanostructured lipid carriers (NLC) in cosmetic dermal products

The first generation of lipid nanoparticles was introduced as solid lipid nanoparticles (SLN), the second, improved generation as nanostructured lipid carriers (NLC). Identical to the liposomes, the lipid nanoparticles (NLC) appeared as products first on the cosmetic market. The article gives an overview of the cosmetic benefits of lipid nanoparticles, that means enhancement of chemical stability of actives, film formation, controlled occlusion, skin hydration, enhanced skin bioavailability and physical stability of the lipid nanoparticles as topical formulations. NLC are on the market as concentrates to be used as cosmetic excipients, special formulation challenges for these products are discussed. NLC appeared also in a number of finished cosmetic products world-wide. An overview of these products is provided including their special effects due to the lipid nanoparticles, lipids used for their production and incorporated cosmetic actives.     

Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo investigation

Dermal therapy is still a challenge due to the difficulties in controlling the active pharmaceutical ingredient (API) fate within the skin. Recently, lipid nanoparticles have shown a great potential as vehicle for topical administration of active substances, principally owing to the possible targeting effect and controlled release in different skin strata. Ketoprofen and naproxen loaded lipid nanoparticles were prepared, using hot high pressure homogenization and ultrasonication techniques, and characterized by means of photo correlation spectroscopy and differential scanning calorimetry. Nanoparticle behavior on human skin was assessed, in vitro, to determine drug percutaneous absorption (Franz cell method) and, in vivo, to establish the active localization (tape-stripping technique) and the controlled release abilities (UVB-induced erythema model). Results demonstrated that the particles were able to reduce drug penetration increasing, simultaneously, the permeation and the accumulation in the horny layer. A prolonged anti-inflammatory effect was observed in the case of drug loaded nanoparticles with respect to the drug solution. Direct as well as indirect evidences corroborate the early reports on the usefulness of lipid nanoparticles as carriers for topical administration, stimulating new and deeper investigations in the field.     

Enhancement of Topical Delivery from Biodegradable Nanoparticles

PURPOSE: To determine whether and how encapsulation of lipophilic compounds in polymeric nanoparticles is able to improve topical delivery to the skin. METHODS: The penetration of octyl methoxycinnamate (OMC; Parsol MCX), a highly lipophilic sunscreen, into and across porcine ear skin in vitro was investigated, subsequent to encapsulation in poly(epsilon-caprolactone) nanoparticles, using tape-stripping. Confocal laser scanning microscopy (CLSM) was used to visualize the distribution of nanoparticles, charged with Nile red (NR), a lipophilic and fluorescent dye. RESULTS: Quantification of OMC in the skin using tape-stripping demonstrated that nanoparticulate encapsulation produced a 3.4-fold increase in the level of OMC within the stratum corneum (SC), although the use of nanoparticles did not appear to increase skin permeation (it was not possible to detect OMC in the receiver compartment after 6 h). The confocal images showed that the fluorescence profile observed in the skin after application of NR-containing nanoparticles was clearly different from that seen following application of NR dissolved in propylene glycol. Two hours postapplication of NR-containing nanoparticles, fluorescence was perceptible at greater depths (up to 60 microm) within the skin. CONCLUSIONS: i) Nanoparticulate encapsulation of OMC increased its "availability" with the SC. ii) The altered distribution of NR when delivered via nanoparticles was due, at least in part, to its altered thermodynamic activity (relative to that in propylene glycol) and, as a result, an increase in its partition coefficient into the SC.     

Importance of using solid lipid microspheres as carriers for UV filters on the example octyl methoxy cinnamate

The aim of this study was to prepare solid lipid microspheres (SLM) of octyl methoxy cinnamate (2-ethylhexyl-p-methoxy cinnamate; OMC) to achieve controlled release, decrease penetration of this UV absorber from skin and improve its photostability. The influence of the carrier on the rate of release was studied in vitro with a cellulose acetate membrane and in vivo from excised rat skin with Franz diffusion cells. The release rate was decreased by up to 13-80% with the SLM formulation. In vivo, penetration of OMC into skin was investigated by HPLC method. It was found out that the rate of penetration is significantly dependent upon the formulation and could be decreased by up to 77% in SLM formulations. When different topical vehicles were compared, OMC was released and penetrated into rat skin more quickly and in greater amount from vehicles containing free OMC than in SLM form. Additionally, photostability was shown to be improved in SLM form.     

Percutaneous penetration/dermal absorption of hair dyes in vitro.

This paper presents an in vitro technique to analyse percutaneous penetration and dermal absorption of hair dyes, topically applied to excised pig skin. Representative examples are given by the radio-labelled hair dyes p-phenylenediamine and bis-(5-amino-1-hydroxyphenyl)-methane. Both compounds were assessed under simulated use conditions and were analysed in representative formulations including the specific conditions for oxidation hair dyes. To be able to differentiate between topically adsorbed and systemically available amounts, the bioavailability of the hair dyes is defined as the amount penetrated and/or remaining in the exposed skin after removing the stratum corneum. Less than 1% of the assessed topically applied dyes was found to be bioavailable in the presence of hydrogen peroxide, typically added to oxidation hair dyes prior to applications. Compared with published results and unpublished in-house in vivo data, the level of confidence was high. Owing to in-house experience over about 5 years in using excised pig skin for measurements of percutaneous penetration and dermal absorption of hair dyes, the technique was found to be successful and appropriate to reduce the number of test animals normally used for toxicological assessments. The essentials of this technique are actually recommended by the SCCNFP (The Scientific Committee on Cosmetic Products and Non Food Products intended for Consumers) for the safety evaluation of cosmetic ingredients, particularly for hair dyes. The corresponding OECD guideline as well as the guidance document has been drafted and is currently in discussion on the level of the national coordinators.     

Differential scanning calorimetry studies on sunscreen loaded solid lipid nanoparticles prepared by the phase inversion temperature method

Solid lipid nanoparticles (SLN) are regarded as interesting carriers to improve sunscreens' safety and effectiveness. In this work, surfactant effects on the physico-chemical properties of SLN loading two of the most widely used UV-filters, octylmethoxycinnamate (OMC) and butylmethoxydibenzoylmethane (BMBM), were evaluated and the interactions between SLN components and loaded UV-filters were investigated by differential scanning calorimetry (DSC). All the SLN showed a mean size ranging from 30 to 95 nm, and a single peak in size distribution. The use of isoceth-20 or oleth-20 as primary surfactants did not provide SLN with suitable physico-chemical properties since: (a) OMC loaded SLN proved unstable; (b) BMBM could not be loaded. OMC or BMBM loaded SLN prepared using ceteth-20 as primary surfactant were stable but their loading capacity lowered when both sunscreens were loaded simultaneously. DSC analyses showed that OMC distributed inside the SLN and caused a decrease of the lipid matrix molecules cooperativity while BMBM did not affect SLN calorimetric behaviour. When OMC and BMBM were loaded together into these SLN, an interaction between BMBM and OMC occurred. These results suggest that the interactions between sunscreens and between sunscreens and SLN components deserve further investigation to evaluate their effect on UV-filter-loaded SLN effectiveness.     

Toxicological profile of diethyl phthalate: a vehicle for fragrance and cosmetic ingredients.

Diethyl phthalate (DEP; CAS No. 84-66-2) has many industrial uses, as a solvent and vehicle for fragrance and cosmetic ingredients and subsequent skin contact. This review focuses on its safety in use as a solvent and vehicle for fragrance and cosmetic ingredients. Available data are reviewed for acute toxicity, eye irritation, dermal irritation, dermal sensitization, phototoxicity, photoallergenicity, percutaneous absorption, kinetics, metabolism, subchronic toxicity, teratogenicity, reproductive toxicity, estrogenic potential, genetic toxicity, chronic toxicity, carcinogenicity, in vitro toxicity, ecotoxicity, environmental fate and potential human exposure. No toxicological endpoints of concern have been identified. Comparison of estimated exposure (0.73 mg/kg/day) from dermal applications of fragrances and cosmetic products with other accepted industrial (5 mg/m(3) in air) and consumer exposures (350 mg/l in water; 0.75 mg/kg/day oral exposure) indicates no significant toxic liability for the use of DEP in fragrances and cosmetic products.     

Lipid nanoparticles as novel delivery systems for cosmetics and dermal pharmaceuticals

INTRODUCTION: Lipid nanoparticles are innovative carrier systems developed as an alternative to traditional vehicles such as emulsions, liposomes and polymeric nanoparticles. Solid lipid nanoparticles (SLN) and the newest nanostructured lipid carriers (NLC) show important advantages for dermal application of cosmetics and pharmaceuticals. AREA COVERED: This article focuses on the main features of lipid nanoparticles, in terms of their preparation and recent advancements. A detailed review of the literature is presented, introducing the importance of these systems in the topical delivery of drugs and active substances. EXPERT OPINION: Lipid nanoparticles are able to enhance drug penetration into the skin, allowing increased targeting to the epidermis and consequently increasing treatment efficiency and reducing the systemic absorption of drugs and cosmetic actives. The complete biodegradation of lipid nanoparticles and their biocompatible chemical nature have secured them the title of 'nanosafe carriers.' SLN and NLC represent a new technological era, which has been taken over by the cosmetic and pharmaceutical industry, which will open new channels for effective topical delivery of substances.     

Nanotechnology, cosmetics and the skin: is there a health risk?

Cosmetic formulations may contain nano-emulsions and microscopic vesicles consisting of traditional cosmetic materials, although it is uncertain whether they should be qualified as actual nanomaterials. Vesicle materials do not penetrate into living human skin. Vesicle formulations may enhance or reduce skin absorption of ingredients, albeit at a limited scale. Sunscreens contain TiO2 or ZnO nanoparticles (NP), which are efficient UV filters. A number of studies suggest that insoluble NP do not penetrate into or through human skin. The results of in vivo toxicity tests showed that TiO2 and ZnO NP are non-toxic. In vitro and in vivo cytotoxicity, genotoxicity, photogenotoxicity, acute toxicity, sensitisation and ecotoxicology studies on TiO2 NP found no difference in the safety profile of micro- or nano-sized materials, all of which were non-toxic. Although some in vitro investigations on TiO2 particles reported cell uptake, oxidative cell damage or genotoxicity, these results may be secondary to phagocytosis of cells exposed to excessive particle concentrations. Studies on wear debris nano- and microparticles support the traditional view that toxicity of small particles is related to their chemistry, rather than their particle size. There is little evidence supporting a general rule that adverse effects of particles on the skin or other tissues increase with smaller particle size, or produce novel toxicities relative to those of larger particles. Overall, the current evidence suggests that nano-sized cosmetic or sunscreen ingredients pose no potential risk to human health, whereas their use in sunscreens has large benefits, such as the protection of human skin against skin cancer.     

Comparison of percutaneous absorption of fragrances by humans and monkeys

The percutaneous absorption of two cosmetic fragrance materials, safrole and cinnamyl anthranilate, as well as of cinnamic alcohol and cinnamic acid, has been measured at occluded and non-occluded application sites. Absorption values were determined in the rhesus monkey in vivo. Absorption through human skin was measured by using excised skin in diffusion cells. Because of the insolubility in water of safrole and cinnamyl anthranilate, a nonionic surfactant solution (6% oleth 20) was used in the receptor chamber of the diffusion cell in order to facilitate the partitioning of the compounds from the skin into the receptor fluid. The relative volatility of the compounds was determined in order to aid in the interpretation of the absorption results. The greatest difference between in vivo and in vitro absorption values occurred with safrole, which was the least well absorbed and the most volatile compound. Cinnamic acid absorption through non-occluded human skin (17.8 +/- 4.9%, mean +/- SEM) was significantly lower than through monkey skin (38.6 +/- 8.3%). The values for absorption through human and monkey skin did not differ significantly for cinnamyl anthranilate (24.0 +/- 5.1% v. 26.1 +/- 2.3%) or cinnamic alcohol (33.9 +/- 7.3% v. 25.4 +/- 4.4%). Occlusion of the skin resulted in greater permeation of all of the compounds; a significant difference in permeability between the two types of skin occurred only with safrole. The fragrances were absorbed well, but their volatility must be considered in a toxicity evaluation. There was reasonable agreement between the values obtained from the studies of the human skin in vitro and the monkey skin in vivo.     

氮酮对鬼臼毒素固体脂质纳米粒透皮性的影响

目的 考察氮酮对鬼臼毒素固体脂质纳米粒透皮性的影响。方法 以大鼠腹部皮肤为屏障，考察氮酮浓度（体积比）对鬼臼毒素固体脂质纳米粒表现透皮系数的影响。结果 当氯酮浓度分别为0，1％，2％，3％。4％，5％，6％时，鬼臼毒素脂质纳誊粒的表观透皮系数（x10^5）分别为24．82，53．05，55．14，43．92，20．57，25．86，23，30。结论 在有效浓度范围内，氮酮可增加鬼臼毒索固体脂质纳米粒的透皮吸收，含不同浓度氮酮的鬼臼毒素固体脂质纳米粒的透皮能力有差异。     

药用库拉索芦荟活性多糖的护肤特性研究

目的研究库拉索芦荟多糖的保湿特性、经皮吸收特性以及皮肤安全性。方法采用超声辅助提取芦荟活性多糖,并通过人体皮肤水分含量和水分散失量测试法对所制备的芦荟活性多糖的保湿特性（包括锁水、保水两个方面）进行评价;Franz扩散池体外透皮吸收法评价其透皮吸收特性;人体斑贴试验评价其皮肤安全性。结果与空白对照组比较,库拉索芦荟多糖可显著提高皮肤水合状态（P〈0.05）,同时降低经皮失水（P〈0.05）;多糖质量浓度为5%时,皮肤渗透速率达到0.2510mg/（h·cm2）,24h累计渗透量达（4.1519±0.0462）mg/cm2;人体皮肤斑贴试验中全部评定为0级反应。结论库拉索芦荟活性多糖对皮肤具有显著的保湿功效以及较强的皮肤渗透力,并且高度安全,可作为优良的保湿添加剂在化妆品等肤用产品中广泛应用。