Topical Delivery of Atraric Acid Derived from Stereocaulon japonicum with Enhanced Skin Permeation and Hair Regrowth Activity for Androgenic Alopecia

Atraric acid (AA) is a phenolic compound isolated from Stereocaulon japonicum that has demonstrated anti-androgen properties and was used to design an alternative formulation for the treatment of alopecia. This new topical formulation was designed using a solvent mixture system composed of ethanol as a volatile vehicle, oleic acid as a permeation enhancer, and water for skin hydration. The ideal topical AA formulation (AA–TF#15) exhibited an 8.77-fold higher human skin flux and a 570% increase in dermal drug deposition, compared to 1% (w/w) AA in ethanol. In addition, compared to other formulations, AA–TF#15 (1% [w/w] AA) activated keratinocytes and human dermal papilla cell proliferation at a concentration of 50 µM AA, which is equivalent to 50 µM minoxidil. Moreover, AA–TF#15 treatment produced a significant increase in hair regrowth by 58.0% and 41.9% compared to the 1% (w/w) minoxidil and oral finasteride (1 mg/kg)-treated mice. In addition, AA–TF#15 showed a higher expression level of aldehyde dehydrogenase 1, β-catenin, cyclin D1, and pyruvate kinase M2 proteins in the skin of AA–TF#15-treated mice compared to that of those treated with minoxidil and oral finasteride. These findings suggest AA–TF#15 is an effective formulation for the treatment of scalp androgenic alopecia.