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Selective induction of apoptosis in the hamster flank sebaceous gland organ by a topical liposome 5‐α‐reductase inhibitor: A treatment strategy for acne
Author(s) -
LI Lingna,
TANG Li,
BARANOV Eugene,
YANG Meng,
AMOH Yasuyuki,
KATSUOKA Kensei,
HOFFMAN Robert M.
Publication year - 2010
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/j.1346-8138.2009.00778.x
Subject(s) - sebaceous gland , liposome , isotretinoin , acne , hamster , pharmacology , endocrinology , testosterone (patch) , prostate , medicine , apoptosis , chemistry , biology , biochemistry , dermatology , cancer
Acne is a very widespread cosmesis problem. Isotretinoin, a synthetic oral retinoid is used to treat acne, which is androgen dependent. Numerous side‐effects occur from this treatment. 5‐α‐Reductase plays a critical role in normal and pathological androgen‐dependent processes. We have taken the approach to develop a selective, effective, topically‐applied 5‐α‐reductase inhibitor to modify unwanted or pathological processes in the pilosebaceous unit such as acne. Toward this goal, we have previously developed a selective liposome hair follicle targeting system. We demonstrate in this report that the 5‐α‐reductase inhibitor N , N ‐diethyl‐4‐methyl‐3‐oxo‐4‐aza‐5α‐androstane‐17β‐carboxamide (4‐MA) incorporated into liposomes induces apoptosis and inhibits growth of the dihydrotestosterone (DHT)‐dependent hamster flank organ sebaceous gland. We have compared topical application of liposome 4‐MA and solvent‐formulated 4‐MA and observed selective efficacy of topical application of liposome 4‐MA by the reduction of size and induction of apoptosis only in the treated hamster flank organ. Apoptosis induced by liposome 4‐MA in the treated flank organ sebaceous gland cells was observed both by assays for DNA fragments (transferase deoxytidyl uridine end labeling) and by observation of condensed and fragmented nuclei. When 4‐MA was topically applied formulated in ethanol and glycerol without liposomes, the selective efficacy was lost. Liposome 4‐MA did not significantly affect prostate weight, testosterone/DHT ratios or bodyweight gain compared to controls indicating safety as well as efficacy of topical application of liposome 4‐MA for pathological processes such as acne.