J Pharm Sci 1997 May;86(5):573-8
Importance of sebaceous glands in cutaneous penetration of an antiandrogen:
target effect of liposomes.
Bernard E, Dubois JL, Wepierre J.
Laboratoire de dermophamacologie, Faculte de Pharmacie, Chatenay-Malabry, France.
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.