TRANSEPIDERMAL DELIVERY OF BETA-BLOCKING-AGENTS - EVALUATION OF ENHANCER EFFECTS USING STRATUM-CORNEUM LIPID LIPOSOMES

The effect of the penetration enhancers Atone, 1-dodecanol, and dodecy l-2-(N,N-dimethylamino)propionate (DDAIP) on the structural integrity of liposomes composed of stratum corneum (SC) lipids was studied. With increasing enhancer concentration (0-1.5 mM) in the incubation medium (30% w/w aqueous ethanol), the lipid bilayer structure was found to b ecome more disordered, as demonstrated by a decrease in 1,6-diphenyl-1 ,3,5-hexatriene (DPH) fluorescence anisotropy, and the efflux of the e ntrapped hydrophilic fluorescent marker, calcein, was found to increas e. The lipid fluidizing effects of Atone and DDAIP were stronger than that of 1-dodecanol. In addition, transport of propranolol hydrochlori de and sotalol hydrochloride, administered as solutions in 45% w/w aqu eous ethanol containing 0-10 mM enhancer, was investigated across huma n epidermis in vitro. The flux enhancements of Atone and DDAIP were mo re pronounced with the hydrophilic sotalol and increased with increasi ng enhancer concentration, whereas 1-dodecanol was found to have a neg ligible effect. The flux of the lipophilic propranolol, on the other h and, was only slightly augmented by the enhancers. The lipid disorderi ng effects and flux enhancement (especially that of the hydrophilic dr ug) followed a similar trend demonstrating the importance of SC lipid interactions as a mode of action of the enhancers studied.