A multifunctional cholesterol-free liposomal platform based on protopanaxadiol for alopecia therapy

Liposome could form a long-term drug reservoir in the skin for sustained drug release, which is beneficial to improving efficacy and alleviating adverse effects. Thus, it has become a better option for anti-alopecia drugs delivery. However, cholesterol used as the fluidity buffer in conventional liposomes is a precursor for testosterone biosynthesis, which could convert to dihydrotestosterone, resulting in hair follicle damage and potentiating hair loss. To overcome the limitations, in this study we prepared a cholesterol-free liposome (PPD-Lip) using protopanaxadiol (PPD) instead of cholesterol to avoid the biosynthesis of testosterone which is adverse to alopecia therapy. PPD-Lip also worked as an active ingredient to facilitate hair growth by promoting dermal papilla cells proliferation and migration, upregulating mRNA levels of hair growth-related positive regulators, and accelerating angiogenesis in vitro. Meanwhile, it promoted hair regrowth in telogen and androgenetic alopecia mice models in vivo. In addition, our study showed that as the liposomal vehicle, PPD-Lip loaded with dutasteride exerted a stronger efficacy in the treatment of androgenetic alopecia and such a strategy could extend to other anti-alopecia agents. To the best of our knowledge, being easy for clinical transformation, the PPD-based liposomal delivery system provides a promising and multifunctional alternative platform for the delivery of alopecia treatment agents.