Chen Yangyan, Ren Tao, Wu Wentao, Yang Beibei, Lu Anqi, Pan Ke, Xu Jing, Lu Chao, Quan Guilan, Wu Chuanbin, Pan Xin, Peng Tingting
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, College of Pharmacy, Jinan University, Guangzhou 511436, China.
J Control Release. 2025 Mar 10;379:636-651. doi: 10.1016/j.jconrel.2025.01.034. Epub 2025 Jan 24.
Existing treatments for androgenetic alopecia (AGA) are unsatisfactory, owing to the two major reasons: (1) Oxidative stress and vascularization deficiency in the perifollicular microenvironment provoke the premature senescence of hair follicles, limiting the transformation of hair growth cycle from the telogen to the anagen phase; (2) The amount of drug delivered to the perifollicular region located in the deep dermis is very limited for passive drug delivery systems. Herein, we developed a gas-propelled microneedle patch integrated with ferrum-chelated puerarin/quercetin nanoparticles (PQFN) to increase drug accumulation in hair follicles and reshape the perifollicular microenvironment for improved hair-regenerating effects. PQFN can rejuvenate testosterone (Tes)-induced senescence of dermal papilla cells by scavenging ROS, restoring mitochondrial function, regulating signaling pathways related to hair regeneration, and upregulating hair growth-promoting genes. PQFN more efficiently promoted endothelial cell proliferation, migration, and tube formation than ferrum-chelated quercetin nanoparticles (QFN) because of puerarin's proangiogenic effects. Compared with passive MNs, gas-propelled MNs promoted drug diffusion and permeation into deeper skin layers, resulting in significantly higher drug accumulation in hair follicles. Pharmacodynamic studies on an AGA mouse model further showed that PQFN-loaded active MNs achieved higher hair coverage by alleviating oxidative stress, promoting angiogenesis, and rejuvenating senescent cells. Therefore, this study presents a novel "anti-hair follicle aging" treatment strategy for AGA.
由于两个主要原因，现有的雄激素性脱发（AGA）治疗方法并不令人满意：（1）毛囊周围微环境中的氧化应激和血管化不足会引发毛囊过早衰老，限制毛发生长周期从休止期向生长期的转变；（2）对于被动给药系统而言，输送到位于真皮深层的毛囊周围区域的药物量非常有限。在此，我们开发了一种集成了铁螯合葛根素/槲皮素纳米颗粒（PQFN）的气体驱动微针贴片，以增加毛囊中的药物蓄积，并重塑毛囊周围微环境，从而改善毛发再生效果。PQFN可以通过清除活性氧、恢复线粒体功能、调节与毛发再生相关的信号通路以及上调促进头发生长的基因，使睾酮（Tes）诱导的真皮乳头细胞衰老恢复活力。由于葛根素的促血管生成作用，PQFN比铁螯合槲皮素纳米颗粒（QFN）更有效地促进内皮细胞增殖、迁移和管腔形成。与被动微针相比，气体驱动微针促进药物扩散并渗透到更深的皮肤层，导致毛囊中的药物蓄积显著更高。对AGA小鼠模型的药效学研究进一步表明，负载PQFN的活性微针通过减轻氧化应激、促进血管生成和使衰老细胞恢复活力，实现了更高的毛发覆盖率。因此，本研究为AGA提出了一种新型的“抗毛囊衰老”治疗策略。
