IMPORTANCE OF SEBACEOUS GLANDS IN CUTANEOUS PENETRATION OF AN ANTIANDROGEN - TARGET EFFECT OF LIPOSOMES

The significance of the sebaceous gland pathway in the cutaneous perme ation of an antiandrogen, 4-[3-(4-hydroxybutyl)-4,4-dimethyl-2,5-dioxo - 1-imidazolidinyl]-2-(trifluoromethyl)benzon (RU 58841), was studied with normal hairless rat skin and an induced scar hairless rat skin wi thout sebaceous glands. RU 58841 was dissolved in an alcoholic solutio n and encapsulated in liposomes for comparison. After 24 h, the cumula tive percentage of RU 58841 absorbed in vitro was 3-4-fold higher in t he normal skin than in the scar skin; in the case of liposomes, the ac cumulation of the drug in the normal dermis was significantly higher t han in the scar one. In the in vivo cutaneous distribution, the epider mis and dermis of the normal skin contained higher amounts of RU 58841 than the scar skin (ninefold with the solution and 16-fold with lipos omes). An autoradiography study showed that with the solution, the dru g was mainly localized in the stratum corneum/epidermis, and with the liposomes, the drug was mainly localized in the sebaceous glands. We c oncluded that the sebaceous glands constituted the main pathway for RU 58841. The alcoholic solution encouraged the localization of the drug into the stratum corneum, whereas liposomes targeted the sebaceous gl ands.