Modulation of caffeine skin delivery by carrier design: liposomes versus permeation enhancers

Delivery systems for caffeine have been designed for two different purposes: (1) enhancing drug permeation through the skin for systemic delivery and (2) accumulating drug reservoir in the skin for local delivery. Caffeine exhibited concentration-dependent growth inhibition of normal and psoriatic human fibroblasts, as well as 3T3 mouse fibroblasts. High flux of caffeine through the skin was obtained from an aqueous solution containing an enhancing mixture of 20% Transcutol and 10% oleic acid. The presence of the enhancers resulted in caffeine flux 40 times greater than in their absence. The high flux of caffeine through the skin in vitro which was obtained using the enhancing composition was shown to be parallel to increased serum concentrations of drug in rats in vivo. Application of caffeine in aqueous solution containing enhancing mixture resulted in high serum concentrations of 50-60 μ ml after 1 h, which remained high for at least 12 h following. The greatest caffeine accumulation in the skin was measured from small liposomal vesicles, 2260 solμg cm², this being 3 times greater than from aqueous solution containing enhancers, the system which exhibited the second largest accumulation of drug in the skin. Using quantitative skin autoradiography, it was found that after 24 h, the greatest concentration of caffeine (280 μg g tissue) was localized in the epidermis and the lowest amount (50 μg g tissue) in the dermis. In addition, a relatively high concentration of caffeine was found in the appendages.