Department of Plastic and Reconstructive Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Theranostics. 2023 Jun 26;13(11):3675-3688. doi: 10.7150/thno.84118. eCollection 2023.
Hair loss is a growing esthetic condition driven by complex mechanisms that has numerous psycho-social implications. Conventional drug applications usually focus on a single treatment target, and the penetration depth restricts the post-delivery effect. We fabricated a curcumin-zinc framework (ZnMOF) encapsulated gamma-polyglutamic acid (γ-PGA) microneedle patch (ZnMOF-MN) as a multifunctional biosafe transdermal drug delivery system. ZnMOF was characterized with the field emission scanning electron microscope (FE-SEM), dynamic light scattering (DLS), elemental mapping, and X-ray diffraction (XRD). The topographical and hygroscopic features of ZnMOF-MN were characterized with SEM. The ZnMOF release profile and the penetration of ZnMOF-MN were also evaluated. The anti-oxidant, anti-apoptosis, and antiandrogen effects of ZnMOF solution and ZnMOF-MN extract were studied on mouse dermal papilla cells (DPCs). Two animal models (in C57BL/6 mice), including androgenic alopecia (AGA) model and wound healing model, were used to identify the therapeutic effect of ZnMOF-MN on hair regrowth and wound healing . Hair follicles, surrounding vessels (CD31+), and proliferating cells (Ki67+) were evaluated by histological staining. ZnMOF crystals were cone-shaped nanoparticles with a size distribution of 424.9 ± 59.01 nm. ZnMOF-MN patch can create temporary holes in the skin to directly and evenly deliver bioactive ZnMOF particles to the targeted depth and achieve a steady and sustained release of Zn and curcumin. , ZnMOF significantly improved the viability of DPCs against the excess reactive oxygen species (ROS) and inhibited the apoptosis induced by zinc deficiency. In addition, it also reversed the inhibitory effects of dihydrotestosterone (DHT) infiltration. Moreover, the ZnMOF-MN treatment has been proved to accelerate wound healing and increase hair follicles in wound healing models, and improved the hair regrowth in AGA animal models. Enhanced capillary density and cell proliferation observed in the CD31+ and Ki67+ staining of ZnMOF-MN group in both animal models also suggested that ZnMOF can facilitate angiogenesis and promote cell proliferation in the skin, respectively. The ZnMOF-MN treatment is a comprehensive solution with excellent therapeutic efficacy and patient-friendly features for promoting hair growth under various clinical conditions.
脱发是一种日益严重的美容问题,其产生机制复杂,具有诸多心理社会影响。传统药物应用通常侧重于单一的治疗靶点,且药物渗透深度限制了其后续效果。我们制备了一种姜黄素-锌框架(ZnMOF)封装γ-聚谷氨酸(γ-PGA)微针贴片(ZnMOF-MN)作为一种多功能生物安全经皮药物递送系统。采用场发射扫描电子显微镜(FE-SEM)、动态光散射(DLS)、元素映射和 X 射线衍射(XRD)对 ZnMOF 进行了表征。采用扫描电子显微镜(SEM)对 ZnMOF-MN 的形貌和吸湿性特征进行了表征。还评估了 ZnMOF 的释放曲线和 ZnMOF-MN 的渗透情况。研究了 ZnMOF 溶液和 ZnMOF-MN 提取物对小鼠真皮乳头细胞(DPC)的抗氧化、抗凋亡和抗雄激素作用。使用两种动物模型(C57BL/6 小鼠),包括雄激素性脱发(AGA)模型和伤口愈合模型,来确定 ZnMOF-MN 对毛发生长和伤口愈合的治疗效果。通过组织学染色评估毛囊、周围血管(CD31+)和增殖细胞(Ki67+)。ZnMOF 晶体为锥形纳米颗粒,粒径分布为 424.9±59.01nm。ZnMOF-MN 贴片可在皮肤中制造临时孔,将生物活性 ZnMOF 颗粒直接均匀地递送至靶向深度,并实现 Zn 和姜黄素的稳定持续释放。ZnMOF 显著提高了 DPC 对过量活性氧(ROS)的活力,并抑制了锌缺乏引起的细胞凋亡。此外,它还逆转了二氢睾酮(DHT)渗透的抑制作用。此外,ZnMOF-MN 治疗已被证明可加速伤口愈合并增加伤口愈合模型中的毛囊,改善 AGA 动物模型中的毛发生长。在两种动物模型的 CD31+和 Ki67+染色中观察到的增强的毛细血管密度和细胞增殖表明,ZnMOF 可分别促进皮肤中的血管生成和促进细胞增殖。ZnMOF-MN 治疗是一种综合解决方案,具有优异的治疗效果和患者友好的特点,可在各种临床情况下促进头发生长。