Radiofrequency Microporation Enhances Topical Minoxidil Delivery and Hair Regeneration in Androgenetic Alopecia

Background/Objectives: Androgenetic alopecia (AGA) is the most prevalent form of hair loss. Although topical minoxidil (MNX) is widely used to treat AGA, its efficacy is limited by poor penetration across the stratum corneum. This study evaluated radiofrequency (RF) microporation as a means of enhancing cutaneous MNX delivery and hair-regrowth efficacy in a dihydrotestosterone (DHT)-induced AGA mouse model. Methods: RF-induced skin permeabilization and barrier recovery were assessed in rats using methylene blue and rhodamine B staining. In vivo skin deposition and pharmacokinetic studies were conducted to quantify cutaneous MNX accumulation and systemic exposure. Hair-regrowth efficacy was evaluated in DHT-treated mice. Results: RF microporation generated transient microchannels in the stratum corneum, increased rhodamine B penetration into deeper skin layers, and allowed substantial barrier recovery within 24 h. RF pretreatment significantly increased MNX deposition in the epidermis/dermis by 2.40-fold at 1 h and 1.94-fold at 3 h compared with topical MNX alone. RF-assisted topical administration resulted in a relative bioavailability of 11.17%, compared with 4.74% for topical administration without RF, while dose-normalized systemic exposure remained substantially lower than that following oral administration. In the AGA model, RF-assisted MNX treatment significantly increased hair coverage, length, and shaft thickness. Histological analysis further showed more prominent follicular structures in the RF-assisted MNX groups. Conclusions: RF microporation creates transient microchannels that enhance cutaneous MNX delivery and improve hair-regrowth efficacy. Importantly, RF-assisted topical administration maintained substantially lower systemic exposure than oral administration, supporting its potential as a needle-free strategy for topical AGA therapy and further translational evaluation.