Positively charged chitosan-dissolving microneedles promote follicular accumulation of finasteride nanocrystals to treat androgenetic alopecia

An imbalance of androgens and changes in the follicular microenvironment are the hallmarks of androgenetic alopecia (AGA), a complex disorder that causes follicular shrinkage and progressive hair loss. Although the main goal of finasteride (FIN) monotherapy is androgen control, it has systemic drawbacks such as psychiatric side effects and sexual dysfunction. FIN nanocrystals (NCs) stabilized by cationic chitosan (CS) were added to dissolving microneedles (MNs) to improve follicle targeting while reducing systemic exposure. When CS was applied to the 167.20 ± 0.01 nm FIN-NCs, which had a zeta potential of −49.70 ± 2.00 mV, the outcome was positively charged CS-FIN-NCs that ranged in size from 200 to 300 nm. This alteration resulted in improved accumulation in hair follicles (2.65-fold fluorescence enhancement) and an enlarged passive diffusion area (1.48-fold increase). CS-FIN-NCs markedly enhanced folliculogenesis and hair regrowth in a mouse model of AGA. This formulation mechanistically enhances the migration of human umbilical vein endothelial cells by inhibiting TGF-β1, upregulating β-catenin, and promoting angiogenesis. These results demonstrate that CS-FIN-NCs delivered transcutaneously via MNs produce dual therapeutic benefits for the treatment of localized AGA by modulating follicular niches and acting pharmacologically.