Dual-phase release finasteride-loaded microspheres for androgenetic alopecia treatment: rapid intervention and...

The core pathogenesis of androgenetic alopecia (AGA) involves abnormal accumulation of dihydrotestosterone (DHT) within hair follicles. However, while existing oral formulations achieve DHT suppression, their delayed clinical efficacy (3-6 months for visible regrowth) fails to meet the need for early intervention. Additionally, the frequent dosing further compromises sustained DHT control through drug-level fluctuations and adherence challenges, enabling local regeneration. Herein, to achieve rapid DHT suppression and ensure the long-term maintenance of effective drug concentrations for sustained DHT suppression, we have developed finasteride-loaded microspheres (FIN-MS) with dual-phase release characteristics. Through modulation of the manufacturing process and selection of PLGA material, the microspheres achieved sustained FIN release over 28 days. Notably, during phase I (days 0-4), the high concentration of FIN was rapidly released through diffusion driven by the concentration gradient, while in phase II (days 4-28), they maintained sustained and stable daily drug release through programmed degradation of the PLGA matrix. In AGA animal models, FIN-MS significantly reduced early-phase DHT levels and promoted hair regrowth through sustained suppression of DHT production. This therapeutic outcome correlated with the microspheres' release behavior, demonstrating their dual-phase release characteristic, an initial rapid intervention followed by prolonged maintenance control, which suggests a promising strategy to mitigate the issue of delayed onset inherent to existing therapies.