MODULATION OF CAFFEINE SKIN DELIVERY BY CARRIER DESIGN - LIPOSOMES VERSUS PERMEATION ENHANCERS

Delivery systems for caffeine have been designed for two different pur poses: (1) enhancing drug permeation through the skin for systemic del ivery and (2) accumulating drug reservoir in the skin for local delive ry. Caffeine exhibited concentration-dependent growth inhibition of no rmal 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% ole ic acid. The presence of the enhancers resulted in caffeine flux 40 ti mes greater than in their absence. The high flux of caffeine through t he skin in vitro which was obtained using the enhancing composition wa s shown to be parallel to increased serum concentrations of drug in ra ts in vivo. Application of caffeine in aqueous solution containing enh ancing mixture resulted in high serum concentrations of 50-60 mu g/ml after 1 h, which remained high for at least 12 h following. The greate st caffeine accumulation in the skin was measured from small liposomal vesicles, 2260 mu g/cm(2), this being 3 times greater than from aqueo us solution containing enhancers, the system which exhibited the secon d largest accumulation of drug in the skin. Using quantitative skin au toradiography, it was found that after 24 h, the greatest concentratio n of caffeine (280 mu g/g tissue) was localized in the epidermis and t he lowest amount (50 mu g/g tissue) in the dermis. In addition, a rela tively high concentration of caffeine was found in the appendages.