Modelling the Intercellular Lamellar Lipid Structure of Human Stratum Corneum for Drug Permeation Studies

Résumé du livre

A lamellar matrix comprising cholesterol, water and fatty acids/soaps was prepared to model the permeation of drugs through the intercellular channels of human stratum corneum (SC). X-ray diffraction studies revealed that the matrix consists of both lamellar gel and lamellar liquid crystalline phases and possibly some crystalline lipids at ambient temperature, in good agreement with SC data. The matrix also provided a lamellar structure in polarised light microscopy. Thermal behaviour of the model matrix was studied by differential scanning calorimetry (DSC) and hot-stage microscopy; results showed good correlation with SC data. The effects of geometry of the SC on the permeation of 5-fluorouracil (5-FU) and oestradiol (OE) were modelled through release and permeation studies. Release results showed that the diffusion coefficients of 5-FU and OE in the matrix are greater than the apparent human epidermis values, in good agreement with theoretical considerations. Release experiments were then/combined with permeation studies and the permeability coefficients of 5-FU and OE through human epidermis were predicted from matrix data. The predicted values were in agreement with the observed data. These results indicated that both drugs permeate the SC through intercellular lipids. The effects of cineole and limonene on the permeation of 5-FU and OE through the matrix were investigated. Results revealed that the matrix is able to model the effects of these enhancers on the permeation of OE through human epidermis. The matrix was also able to model the effects of cineole on the diffusivity of 5-FU in the SC as was shown by release results. However, the matrix failed to model the enhancement effect of limonene toward permeation of 5-FU through human epidermis. The difference might indicate that limonene increases the permeability of 5-FU in part through interactions with human SC proteins. Hot-stage microscopy and DSC studies suggested ....