Liu Xiaoli, Li Xiaojuan, He Weijun, Han Xiaoyu, Xiao Ting, Guo Shiqi, Jia Yujie, Lin Liqun, Yang Ming, Wang Li, Xu Yuehong
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, 518120, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Drug Deliv Transl Res. 2025 Aug 29. doi: 10.1007/s13346-025-01953-2.
Acne is a multifactorial dermatological condition driven by Propionibacterium acnes (P. acnes) infection, inflammation, and sebum dysregulation. While essential oils, such as Angelica sinensis (Danggui) essential oil (AEO), exhibit antimicrobial and anti-inflammatory properties, their clinical application is hindered by poor solubility, stability, and skin penetration. To address these limitations, we developed hydroxypropyl-β-cyclodextrin (HPCD)-complexed AEO-loaded microneedles (AEO@HPCD MNs) using hyaluronic acid for enhanced transdermal delivery. The optimized AEO@HPCD MNs demonstrated superior mechanical strength, rapid dissolution, and efficient cargo release. In vitro studies confirmed potent antibacterial activity against P. acnes, while in vivo experiments revealed significant reductions in acne lesion size and IL-1β levels. RNA sequencing of treated acne lesions identified key downregulated genes (Fpr1, Rarres2, Cxcl5, Gbp3, Hck, Gbp7, Librb4a, Psmb8) and enriched pathways, including innate immunity and inflammatory responses. Notably, AEO@HPCD MNs suppressed 5α-reductase and fatty acid synthase (FAS) expression, demonstrating-for the first time-AEO's ability to normalize sebum production. Mechanistically, AEO@HPCD MNs exert multifaceted therapeutic effects: (1) direct antibacterial activity against P. acnes, (2) suppression of inflammatory and immune-related pathways through modulation of Toll-like receptor, NOD-like receptor, and cytokine-cytokine receptor signaling pathways, (3) regulation of sebum production via lipid-metabolic gene expression modulation, and (4) enhanced delivery efficiency and microenvironment modification through the physical action of microneedles, collectively contributing to synergistic acne therapy. This study develops a microneedle delivery platform that addresses both essential oil instability and inclusion complex delivery challenges while targeting multiple acne pathogenic factors. The AEO@HPCD MNs provide a safe, minimally invasive, multifunctional therapeutic strategy for acne treatment.
痤疮是一种由痤疮丙酸杆菌（P. acnes）感染、炎症和皮脂调节异常驱动的多因素皮肤病。虽然诸如当归精油（AEO）等精油具有抗菌和抗炎特性，但其临床应用受到溶解度差、稳定性差和皮肤渗透性差的阻碍。为了解决这些局限性，我们使用透明质酸开发了负载羟丙基-β-环糊精（HPCD）复合AEO的微针（AEO@HPCD MNs），以增强透皮给药。优化后的AEO@HPCD MNs表现出优异的机械强度、快速溶解和高效的药物释放。体外研究证实了其对痤疮丙酸杆菌的强大抗菌活性，而体内实验显示痤疮病变大小和IL-1β水平显著降低。对治疗后的痤疮病变进行RNA测序，确定了关键的下调基因（Fpr1、Rarres2、Cxcl5、Gbp3、Hck、Gbp7、Librb4a、Psmb8）和富集途径，包括固有免疫和炎症反应。值得注意的是，AEO@HPCD MNs抑制了5α-还原酶和脂肪酸合酶（FAS）的表达，首次证明了AEO使皮脂分泌正常化的能力。从机制上讲，AEO@HPCD MNs发挥多方面的治疗作用：（1）对痤疮丙酸杆菌的直接抗菌活性，（2）通过调节Toll样受体、NOD样受体和细胞因子-细胞因子受体信号通路抑制炎症和免疫相关途径，（3）通过脂质代谢基因表达调节来调节皮脂分泌，以及（4）通过微针的物理作用提高给药效率和改善微环境，共同促成协同性痤疮治疗。本研究开发了一种微针给药平台，该平台在解决精油不稳定性和包合物递送挑战的同时，还针对多种痤疮致病因素。AEO@HPCD MNs为痤疮治疗提供了一种安全、微创的多功能治疗策略。
