Finasteride-loaded phospholipid-bile salt mixed micelles for targeted follicular delivery in androgenetic alopecia

Androgenetic alopecia (AGA) is driven by elevated scalp dihydrotestosterone. Although oral finasteride (FNS) is clinically effective, its long-term use is limited by sexual and psychological adverse effects. Topical delivery has the potential to reduce systemic exposure; however, conventional formulations still permit considerable transdermal absorption. To overcome this limitation, phospholipid-bile salt mixed micelles composed of egg phosphatidylcholine (EPC) and sodium cholate (SC) were developed using a remote-loading strategy to enhance follicular targeting while restricting systemic uptake. The optimised formulation, containing EPC-to-SC and lipid-to-drug molar ratios of 0.7:0.3 and 20:1, respectively, produced uniform spherical micelles (285 ± 10.9 nm; polydispersity index 0.385 ± 0.01; -36.3 ± 0.6 mV). High-performance liquid chromatography analysis indicated an encapsulation efficiency of 98.5 ± 0.5% and confirmed sustained FNS release over 48 h. Confocal microscopy of fluorescein isothiocyanate-loaded micelles demonstrated efficient follicular deposition with minimal lateral diffusion. In an AGA mouse model, the micelles markedly improved hair regrowth, increased follicle number and length, and enhanced follicular proliferation compared with a hydroalcoholic FNS solution. Notably, serum dihydrotestosterone levels remained higher in the micelle-treated group, indicating reduced systemic absorption. Collectively, these findings support the strong translational potential of EPC-SC micelles as a safer and more effective topical strategy for AGA management.