The interest in alternative material systems and delivery methods for treatment of androgenetic alopecia has been increasing in the recent decades. Topical application of valproic acid (VPA), an FDA-approved anticonvulsant drug, has been shown to effectively stimulate hair follicle (HF) regrowth by upregulating Wnt/β-catenin, a key pathway involved in initiation of HF development. Moreover, a majority of studies have suggested that cutaneous wound re-epithelialization is capable of inducing HF through Wnt/β-catenin pathway. Here, we report fabrication and evaluation of a novel VPA-encapsulating dissolving microneedle (DMN-VPA) that creates minimally invasive dermal micro-wounds upon application, significantly improving the VPA delivery efficiency. DMN-VPA not only delivers encapsulated VPA with higher accuracy than topical application, it also stimulates wound re-epithelialization signals involved in HF regrowth. Through a series of in vivo studies, we show that micro-wounding-mediated implantation of DMN-VPA upregulates expression of Wnt/β-catenin pathway, alkaline phosphatase, proliferating cell nuclear antigen, loricrin and HF stem cell markers, including keratin 15, and CD34 more effectively than topical application.

近几十年来，人们对替代材料系统和治疗雄激素性脱发的方法的兴趣不断增长。丙戊酸（VPA）是FDA批准的抗惊厥药的局部应用，已被证明可通过上调Wnt /β-catenin（参与HF形成的关键途径）来有效刺激毛囊（HF）的再生。此外，大多数研究表明，皮肤伤口再上皮形成能够通过Wnt /β-catenin途径诱导HF。在这里，我们报告制造和评估新型VPA封装的溶解微针（DMN-VPA），该微针在应用时会产生微创皮肤微伤口，从而显着提高了VPA的输送效率。DMN-VPA不仅以比局部应用更高的精度提供封装的VPA，它也刺激与HF再生长有关的伤口再上皮信号。通过一系列体内研究表明，微创介导的DMN-VPA植入可更有效地上调Wnt /β-catenin途径，碱性磷酸酶，增殖细胞核抗原，loricrin和HF干细胞标记（包括角蛋白15和CD34）的表达比局部应用。