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U. Münster (1),
K. Jores (2), W. Mehnert (2), M. Schaller (3), H.C. Korting (3) and M. Schäfer
Korting (1) Antidrogen targeting to the hair follicle
Depts. of Pharmacy (1) Pharmacology,
(2) Pharmaceutical Technology) Freie Universität D 14195 Berlin
( 3) Dermatology, Ludwig MaximiliansUniversität, D 80337 München
Acne vulgaris and androgenetic alopecia are linked to endogenous
androgen production. In man systemic side effects exclude even topical treatment
by androgen receptor antagonists. This, however, may become possible by antiandrogen
targeting to the hair follicle. Here we present the Penetration Profile of a new
potent antiandrogen RU 58841 into porcine skin comparing various vehicles including
drug carrier systems. Penetration studies were carried out using the Franz diffusion
cell. After 6 h incubation excessive material was removed and the skin was Tesa
stripped and cut into 100pm slices. Dried extracts of the slices and Tesa strips
were analysed by HPLC. Moreover, RU 58841 metabolism in cultured human foreskin
keratinocytes and fibroblasts was investigated. When applied as an ethanolic solution
(50p1) up to 3 % of the applied drug penetrated the tissue and 53 to 77 % of the
penetrated substance was recovered by tesa stripping. RU 58841 penetration decreased
in the following order . ethanolic solution > "Elektrodengel DAS"
> "nichtionische hydrophile Creme NRF". RU 58841 was not metabolised
in any of the porcine skin sampies nor in human foreskin keratinocytes and fibroblasts.
To demonstrate drug targeting to the hair follicle silver labelled solid lipid
nanoparticles (SLN) were applied to porcine skin, too. Intact silver labelled
SLN were detectable in deeper layers of the hair follicle. Therefore the association
of antiandrogens with SLN may allow for topical therapy of acne and androgenetic
alopecia not only in women but also in men. nach
oben
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