Investigation of drug partition property in artificial sebum
ABSTRACT Targeted delivery of a therapeutic agent into the hair and sebaceous follicles greatly depends on the extent of drug partitioning/diffusion in the sebum. The objective of the present research was to develop a method to determine the sebum partition coefficient in order to facilitate the selection of sebum-targeted drug candidates. Partition coefficients of model drugs with different chemical structures and 4-hydroxybenzoate series compounds were measured in artificial sebum/water (K(sebum)) and human stratum corneum/water (K(sc)) at 37 degrees C. The relationship was evaluated between logK(sebum), logK(sc) and clogP. The results of the partition coefficient studies indicate that the K(sebum) of some drugs was significantly higher than the K(sc), whereas some drugs showed lower or similar K(sebum) when compared with K(sc). Overall, a relatively poor correlation was observed between logK(sebum), logK(sc) and clog P. However, a linear relationship exists between logK(sebum) and clog P in the 4-hydroxybenzoate series compounds, indicating that K(sebum) depends on the lipophilicity and chemical structure of the compounds. The results of the present study demonstrate that K(sebum) is different from K(sc) and calculated P and is likely to be a critical parameter reflecting drug delivery into hair and sebaceous follicles.
- [Show abstract] [Hide abstract]
ABSTRACT: Sebaceous glands secrete an oily sebum into the hair follicle. Hence, it is necessary to understand the drug partition and diffusion properties in the sebum for the targeted delivery of therapeutic agents into the sebum-filled hair follicle. A new method was developed and used for determination of sebum flux of topical therapeutic agents and other model compounds. The drug transport through artificial sebum was conducted using sebum loaded filter (Transwell) as a membrane, drug suspensions as donor phases and HP-beta-CD buffer solution as a receiver phase. The experiment was performed at 37 degrees C for 2h. The results of the drug transport studies indicate that the flux (J(sebum)) through the artificial sebum is compound dependent and a bell-shaped curve was observed when logJ(s) versus alkyl side chain length of the compounds that proved to be different from the curves obtained upon plotting logJ skin versus clogP for the same compounds, indicating the possibility to select appropriate compounds for sebum targeted delivery based on the differences in the skin flux and sebum transport profiles of the molecules.International Journal of Pharmaceutics 01/2008; 345(1-2):88-94. DOI:10.1016/j.ijpharm.2007.05.043 · 3.65 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To understand drug delivery to the sebum filled hair and sebaceous follicles, it is essential to use an artificial sebum as a surrogate of the human sebum for the investigation of drug transport properties. Artificial sebum L was developed in-house based on the chemical similarity to human sebum. The partition and diffusion of model compounds (ethyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate, and hexyl 4-hydroxybenzoate) were measured in human sebum, hamster ear and body sebum (a commonly used animal model), and four representative artificial sebum samples (N, S, F, and L) in which artificial sebums, N, S and F were selected based on the available literature. DSC and NMR studies were also conducted on all sebums to compare their melting properties and chemical compositions. In vitro studies show that the partition coefficients of the three model compounds in artificial sebum L were similar to that of human sebum, whereas the hamster ear and body sebum, and other three artificial sebum samples were different from that of human sebum. Additionally, the in vitro sebum flux (microg/(cm(2)min) of three model compounds through artificial sebum L was closer to that of human sebum when compared with the other three artificial sebum (N, S and F), hamster body and hamster ear sebum. The results of this study indicate that the artificial sebum L could be used as an alternative to human sebum, as the physicochemical properties of this artificial sebum is relatively similar to human sebum.International Journal of Pharmaceutics 10/2008; 367(1-2):37-43. DOI:10.1016/j.ijpharm.2008.09.025 · 3.65 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Materials in contact with liquids on the human skin surface may dissolve and permeate into skin. Release and permeation of chemicals in contact with skin is often estimated in vitro using artificial skin liquids, although sebum lipids are generally not included in these models. The purposes of this research were to develop a representative artificial sebum that contains the appropriate types of lipids at levels that match human values and quantitatively characterize the model to understand its utility for in vitro testing. Artificial sebum that consisted of 10 lipids at proportions that closely resembled human sebum was characterized using thin layer chromatography under a variety of storage and use conditions (dry and liquid, 4°C and 32°C, with and without vitamin E) for 28 days. Levels of sebum constituents maintained in solution and dry at 4°C were stable through the duration of the test period. Levels of all sebum lipids maintained dry at 32°C were stable in the presence of vitamin E; however, squalene oxidized rapidly in the absence of vitamin E. Liquids on the human skin surface consist of sebum and sweat with minor amounts of cellular debris and intercellular lipid from the stratum corneum. The relative importance of each component for release of chemicals from materials in contact with skin will depend upon the type of material (metal, organic, etc.). A model artificial sebum was formulated and characterized to aid researchers in understanding potential release of chemicals from materials in contact with skin and subsequent partitioning and absorption. les éléments en contact avec les liquides de surface de la peau humaine peuvent se dissoudre et pénétrer dans la peau. La libération et la pénétration de produits chimiques en contact avec la peau sont souvent évalués in vitro en utilisant des liquides cutanés artificiels, bien que les lipides de sébum ne soient généralement pas inclus dans ces modèles. les buts de ce travail étaient de développer un sébum artificiel représentatif contenant les types de lipides appropriés aux concentrations qui correspondent aux valeurs humaines et de caractériser quantitativement ce modèle pour comprendre son utilité lors de test in vitro. Un sébum artificiel consisté de 10 lipides en proportion proches de celles du sébum humain a été caractérisé en utilisant la chromatographie de couche mince dans divers conditions de conservation et d’utilisation (sec et liquide, 4°C et 32°C, avec et sans vitamine E) pendant 28 jours. les proportions des constituants du sébum maintenu en solution et sécher à 4°C étaient stables durant la durée du test. Ceux du sébum maintenu sec à 32°C étaient stables en présence de vitamine E; cependant, le squalène s’oxydait rapidement en absence de vitamine E. les Liquides de surface de la peau humaine consistent en du sébum, de la sueur avec des quantités mineures de débris cellulaires et des lipides intercellulaires du stratum corneum. L’importance relative de chaque composant pour la libération de molécules à partir de produits en contact avec la peau dépendra du type de produit (métallique, biologique, etc.). Un modèle de sébum artificiel a été formulé et caractérisé pour aider des chercheurs dans la compréhension de la libération de molécules à partir de produits en contact avec la peau et du partage et de l’absorption qui en découle.International journal of cosmetic science 05/2010; 32(5). DOI:10.1111/j.1468-2494.2010.00561.x · 1.45 Impact Factor