Mechanism of transdermal transport of 5-fluorouracil by terpenes: Carvone, 1,8-cineole and thymol

The effect of terpenes as penetration enhancers (e.g. carvone, 1,8-cineole and thymol) was studied on the in vitro percutaneous absorption of the model hydrophilic compound 5-fluorouracil through porcine epidermis. The above terpenes (5%, w/v) significantly (P < 0.01) increased the permeability coefficient of 5-fluorouracil in comparison to the control. Enhancement in the permeability of 5-fluorouracil by carvone, 1,8-cineole and thymol in comparison to the control was 91.62, 153.75 and 273.75, respectively. Fourier transform infrared (FT-IR) spectroscopy, and in vitro transepidermal water loss (TEWL) studies were undertaken to investigate the effect of enhancers on the biophysical properties of the stratum corneum and macroscopic barrier integrity of the epidermis, respectively, in order to understand the mechanism of percutaneous absorption enhancement of 5-fluorouracil by terpenes. The FT-IR spectrum of the stratum corneum treated with thymol produced a blue shift in the antisymmetric C-H stretching peak to higher wavenumbers, suggesting an increase in the disorder of the acyl chains of the stratum corneum lipids (i.e. increased lipid fluidity). Treatments of the epidermis with enhancers significantly (P < 0.01) enhanced the in vitro TEWL in comparison to the control. (C) 1997 Elsevier Science B.V.