A lamellar matrix model for stratum corneum intercellular lipids. V. Effects of terpene penetration enhancers on the structure and thermal behaviour of the matrix

Abstract

The principal barrier to transdermal delivery of most drugs is the lamellar intercellular lipid domain of the stratum corneum (SC). Previously, we reported a lamellar matrix capable of modelling the structural and barrier properties of the SC lipids and effects of terpene penetration enhancers on the permeation of oestradiol and, to some extent, that of 5-fluorouracil (5-FU) through the SC. The present work is aimed to investigate the interactions of two terpenes (1,8-cineole and (+) limonene) with the matrix. Terpenes (5–40%, w/w) were added to the matrix and their effects studied by hot-stage light microscopy (25–160°C) and differential scanning calorimetry (10–100°C). Results revealed that cineole breaks the matrix into a dispersed system of a lamellar mesomorphic structure in an isotropic liquid at 25 and 32°C (SC temperature), in good correlation with human SC data. Increasing concentrations of limonene caused initially a decrease in the lamellar structure, then a lamellar-to-cubic phase transition and finally, changed the matrix to a dispersed system of crystalline and mesomorphic phases in a continuous liquid phase at 25 and 32°C. The effects of limonene on the structure of the model matrix are in agreement with those reported for SC lipids derived from X-ray diffraction results. Effects of terpenes on the structure of the matrix were related to their actions on the barrier performance of this lamellar model.