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RU 58841(myristate) pro-drug development for topical treatment of acne and androgenetic alopecia

Hair Loss Study Abstract

Acne and androgenetic alopecia are linked to androgen effects and therefore should improve following topical application of antiandrogens. We present a new antiandrogen prodrug, RU 58841-myristate (RUM) for topical therapy. Almost devoid of affinity to the androgen receptor, as derived from investigations in the mouse fibroblast cell line 29 +/GR +, RUM is rapidly metabolised to the potent antiandrogen RU 58841 by cultured human foreskin fibroblasts and keratinocytes, male occipital scalp skin dermal papilla cells, and by cells of the sebaceous gland cell line SZ95. In order to improve a specific targeting of the hair follicle, RUM was loaded on solid lipid nanoparticles (SLN), which are already known to support dermal targeting effects. Physically stable RUM loaded SLN were produced by hot homogenization. Penetration/permeation studies carried out using the Franz diffusion cell proved only negligible permeation of reconstructed epidermis and excised porcine skin within 6 h, implying a more topical action of the drug. Targeting to the hair follicle using SLN was visualised by fluorescence microscopy, following the application of Nile Red labelled SLN to human scalp skin. Transmission electron microscopy (TEM) allowed to detect intact silver labelled SLN in porcine hair follicles of preparations applied to the skin for 24 h. RUM loaded SLN should be considered for topical antiandrogen therapy of acne and androgenetic alopecia.



Munster U, Nakamura C, Haberland A, Jores K, Mehnert W, Rummel S, Schaller M, Korting HC, Zouboulis ChC, Blume-Peytavi U, Schafer-Korting M.



Pharmakologie und Toxikologie, Institut fur Pharmazie, Freie Universitat Berlin, Germany.



Pharmazie. 2005 Jan;60(1):8-12.





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