Importance of sebaceous glands in cutaneous penetration of an antiandrogen: target effect of liposomes.
The significance of the sebaceous gland pathway in the cutaneous permeation of an antiandrogen, 4-[3-(4-hydroxybutyl)-4,4-dimethyl -2,5-dioxo-1-imidazolidinyl]-2-(trifluoromethyl)benzonitrile (RU 58841), was studied with normal hairless rat skin and an induced scar hairless rat skin without sebaceous glands. RU 58841 was dissolved in an alcoholic solution and encapsulated in liposomes for comparison. After 24 h, the cumulative percentage of RU 58841 absorbed in vitro was 3-4-fold higher in the normal skin than in the scar skin; in the case of liposomes, the accumulation of the drug in the normal dermis was significantly higher than in the scar one. In the in vivo cutaneous distribution, the epidermis and dermis of the normal skin contained higher amounts of RU 58841 than the scar skin (ninefold with the solution and 16-fold with liposomes). An autoradiography study showed that with the solution, the drug was mainly localized in the stratum corneum/epidermis, and with the liposomes, the drug was mainly localized in the sebaceous glands. We concluded 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 glands.
Bernard
E
E
Laboratoire de dermophamacologie, Faculté de Pharmacie, Châtenay-Malabry, France.
Dubois
J L
JL
Wepierre
J
J
D000726:Androgen Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001345:Autoradiography; D004337:Drug Carriers; D007093:Imidazoles / Q000493:pharmacokinetics*; D008081:Liposomes; D008297:Male; D009570:Nitriles / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012627:Sebaceous Glands / Q000502:physiology*; D012869:Skin Absorption / Q000502:physiology*
D000726:Androgen Antagonists; D004337:Drug Carriers; D007093:Imidazoles; D008081:Liposomes; D009570:Nitriles; C086458:RU 58841