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Cationic nanoemulsions enable follicle-associated delivery with reduced systemic exposure for combined minoxidil/finasteride therapy against androgenetic alopecia
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DOI：10.1186/s12951-026-04902-4.png)
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Abstract
En 中文
Androgenetic alopecia (AGA) is a widespread condition characterized by progressive follicular miniaturization and hair loss, yet current topical therapies are often limited by insufficient follicular retention and undesired systemic exposure. Herein, we report cationic nanoemulsions specifically designed to promote follicle-associated delivery of two clinically approved anti-AGA drugs with reduced systemic exposure, thereby achieving potent therapeutic efficacy against AGA. The two anti-AGA drugs, minoxidil (MXD) and finasteride (FNA), are incorporated into a cationic polymer-coated nanoemulsion with a favorable nanoscale droplet (72.64 nm), high encapsulation efficiency (90.46% for MXD and 92.44% for FNA), and positively charged surface (zeta potential 51.2 mV). This cationic interface promoted local cutaneous retention and preferential follicle-associated localization, while substantially reducing systemic absorption. In testosterone-induced AGA mouse models, the dual-drug-loaded nanoemulsion outperformed commercial MXD tincture and single-drug formulations in promoting hair regeneration by inhibiting 5α-reductase-mediated dihydrotestosterone production and TGF-β1 signaling, while activating β-catenin and VEGF pathways to reprogram the follicular microenvironment. Importantly, repeated topical application showed good skin compatibility and no obvious systemic toxicity under the tested conditions. These findings highlight a cationic surface-functionalized nanoemulsion strategy that enhances follicle-associated retention while limiting systemic exposure, offering a clinically translatable approach for AGA therapy.
Keywords:
Cationic nanoemulsion
Minoxidil
Finasteride
Localized topical delivery
Androgenetic alopecia
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