雄激素性脱发(AGA),最普遍的临床脱发,由于AGA患者秃头头皮的毛囊周微环境中血管生成基因下调和血管形成不足,因此缺乏安全有效的治疗方法。在这项研究中,设计了一种基于透明质酸(HA)的水凝胶微针(MN),称为V-R-MN,同时加载血管内皮生长因子(VEGF)和新型脱发药物Ritlecitinib,后者封装在可缓慢生物降解的聚羟基链烷酸酯(PHA)纳米颗粒(R-PHANP)中,用于微创AGA治疗。基于HA的水凝胶与PHA纳米颗粒的整合显着增强了微针的机械特性并增强了皮肤渗透效率。由于生物安全,机械强度,和HA水凝胶形成的微针的受控降解性能,V-R-MN能有效穿透皮肤的角质层,在微创中促进VEGF和Ritlecitinib的直接递送,无痛和长期持续释放的方式。V-R-MNs不仅促进毛囊周围的血管生成和改善免疫微环境,促进毛囊细胞的增殖和发育,而且应用MNs对皮肤产生一定的机械刺激也能促进血管生成。与用于AGA治疗的临床药物米诺地尔相比,V-R-MN在AGA模型小鼠中的毛发再生作用的特征在于生长期的快速开始,改善头发质量,更大的覆盖面。这引入了一个新的,临床上更安全,以及更有效的AGA治疗策略,并为其他相关疾病的治疗提供参考。
Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable
polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin\'s stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.