Transcutaneous implantation of valproic acid-encapsulated dissolving microneedles induces hair regrowth. (June 2018)

• Record Type: Journal Article
• Authors: Fakhraei Lahiji, Shayan; Seo, Seol Hwa; Kim, Suyong; Dangol, Manita; Shim, Jiyong; Li, Cheng Guo; Ma, Yonghao; Lee, Chisong; Kang, Geonwoo; Yang, Huisuk; Choi, Kang-Yell; Jung, Hyungil
• Is Part Of: Biomaterials. Volume 167(2018)
• Page Start: 69
• Page End: 79
• Publication Date: 2018-06
• Subjects: Valproic acid -- Dissolving microneedle -- Transdermal drug delivery -- Androgenetic alopecia -- Micro-wounding -- Hair regrowth; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2018.03.019
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: 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.