Development and Evaluation of a Niosome-Integrated Microneedle System for Targeted Follicular Delivery of Ketoconazole in Alopecia Therapy

Androgenic alopecia (AGA) is a difficult skin condition because conventional topical therapies have limited skin penetration and often suffer from poor patient compliance. This study describes the development and evaluation of a novel transdermal delivery system consisting of ketoconazole loaded niosome integrated into a dissolving microneedle array fabricated from the polyvinyl alcohol (PVA) and Gelatin. Ketoconazole niosome were optimized via a factorial design, achieving a narrow particle size of 201 ± 0.3 nm and a high entrapment efficiency of 86 ± 0.63%.These vesicles were successfully incorporated into a PVA-Gelatin polymer matrix. Field Emission Scanning Electron Microscopy (FESEM) confirmed that the microneedles maintained structural integrity and sharp geometry, which are vital for effective skin insertion. Unlike standard niosomal gels that face barriers from the stratum corneum, these microneedles create tiny punctures in the skin to form micro-channels. This allows for direct delivery of the niosomal cargo into the dermis, targeting the hair follicles directly. In vitro and ex vivo release studies showed a controlled, two-phase drug release profile over 24 hours. Importantly, the microneedle system achieved a much higher localized drug retention of 73.33% compared to 52.39% for pure drug-loaded microneedles, confirming the formation of a dermal drug reservoir. In vivo animal studies indicated improved hair growth, evidenced by increased hair shaft diameter, thickness, and deeper follicular elongation into the dermal and subcutaneous layers. These findings suggest that the Ketoconazole niosome loaded microneedle array is a highly effective, localized, and sustained-release platform that overcomes the limitations of current topical treatments for AGA.