Department of Biotechnology, Building 123, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.
Translational Research Center for Protein Function Control, Building 117, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, South Korea.
Biomaterials. 2018 Jun;167:69-79. doi: 10.1016/j.biomaterials.2018.03.019. Epub 2018 Mar 13.
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，人们对治疗雄激素性脱发的替代材料系统和给药方法的兴趣日益增加。已证实，经美国食品和药物管理局批准的抗惊厥药物丙戊酸（VPA）的局部应用通过上调参与毛囊（HF）发育起始的关键途径 Wnt/β-catenin，可有效刺激毛囊再生。此外，大多数研究表明，皮肤创伤的再上皮化能够通过 Wnt/β-catenin 途径诱导 HF。在这里，我们报告了一种新型 VPA 包封溶解微针（DMN-VPA）的制备和评估，该微针在应用时会产生微创的真皮微创伤，显著提高了 VPA 的递送效率。DMN-VPA 不仅比局部应用更准确地递送包封的 VPA，而且还能刺激参与 HF 再生的创伤再上皮化信号。通过一系列体内研究，我们表明，微创伤介导的 DMN-VPA 植入比局部应用更有效地上调 Wnt/β-catenin 通路、碱性磷酸酶、增殖细胞核抗原、兜甲蛋白和 HF 干细胞标志物（包括角蛋白 15 和 CD34）的表达。
