Co-delivery of minoxidil and finasteride via ionic liquid and cyclodextrin-assisted in situ thermosensitive hydrogel for synergistic treatment of androgenic alopecia

Abstract

Androgenic alopecia (AGA), the most prevalent type of progressive hair loss, currently lacks an effective topical treatment regimen. In this study, we synthesized an ionic liquid (IL) to co-solubilize minoxidil (MXD) and finasteride (FIN) and subsequently formulated them into an in situ thermosensitive ionic liquid/cyclodextrin/poloxamer hydrogel (ICPG), termed M + F@ICPG. M + F@ICPG was developed for the transdermal co-delivery of these two drugs, aiming to provide a multipath therapeutic approach for AGA while avoiding the adverse effects commonly associated with oral FIN and topical MXD tincture. The thermosensitive characteristics, skin penetration, hair follicle (HF) targeting efficiency, biosafety, and in vivo therapeutic efficacy of M + F@ICPG were evaluated using an AGA mouse model. Our results demonstrated that M + F@ICPG was a thermosensitive hydrogel, transitioning from solution to gel upon contact with the scalp. Compared to the FIN suspension and MXD tincture, M + F@ICPG significantly enhanced the skin penetration (∼2.2-fold) and retention (∼8.6-fold) of FIN and increased the relative retention of MXD (∼6.3-fold) in the skin. Moreover, M + F@ICPG exhibited a HF targeting index of 1.74 for MXD and 1.46 for FIN, indicating enhanced drug targeting to HF. M + F@ICPG showed superior in vivo efficacy in terms of hair regeneration, anagen recovery, inflammation mitigation, and microvessel reconstruction. The underlying mechanism was attributed to the upregulation of hair growth genes, downregulation of hair loss genes, and reduction of abnormally elevated inflammatory factors. These findings suggest that this novel M + F@ICPG is a promising topical co-delivery system for the synergistic treatment of AGA.