Luan Xi, Zhang Xiaoxuan, Luan Qichen, Gan Jingjing, Wang Yu, Zhao Yuanjin
Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, School of Pharmacy, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Research (Wash D C). 2024 Jul 4;7:0420. doi: 10.34133/research.0420. eCollection 2024.
Microneedles have demonstrated value in targeted treatment of dermatosis. Current investigation aims to enhance the functions and optimize substance delivery to improve therapeutic effects. Here, we present innovative shell-core microneedles with light-pH dual responsiveness for spatiotemporal sequential release of multiple Chinese herb drugs to treat scleroderma. By using a stepwise template-assisted method, we effectively prepare a hydrogel-based core layer containing polydopamine-MXene (P-MXene) loaded with triptolide (TP), and a shell layer composed of polyvinyl alcohol (PVA) encapsulating paeoniflorin (Pae). P-MXene can adsorb the sparingly soluble TP to ensure its encapsulation efficiency and contribute to the synergistic photothermal effect benefitting from its excellent photothermal conversion ability. Besides, PVA can rapidly dissolve upon microneedle piercing into the skin and quickly release the anti-inflammatory and detoxifying Pae, establishing a favorable low-acid subcutaneous environment. In response to pH changes and near-infrared effects, TP is sustainably released from P-MXene and delivered through the swollen pores of the hydrogel. On the basis of these characteristics, we demonstrate that these microneedles could effectively reduce profibrotic key cytokines interleukin-1β and transforming growth factor-β, thereby reducing collagen deposition and decreasing epidermal thickness, ameliorating skin fibrosis and capillary lesion in scleroderma mouse models. These findings highlight the important clinical potential of these microneedles in the treatment of skin diseases.
微针已在皮肤病的靶向治疗中展现出价值。当前的研究旨在增强其功能并优化物质递送以提高治疗效果。在此,我们展示了具有光 - pH双重响应性的创新型核壳微针,用于多种中药的时空顺序释放以治疗硬皮病。通过逐步模板辅助法,我们有效地制备了一种水凝胶基核心层,其包含负载雷公藤内酯醇(TP)的聚多巴胺 - 碳化钛(P - MXene),以及由包裹芍药苷(Pae)的聚乙烯醇(PVA)组成的壳层。P - MXene可吸附微溶性的TP以确保其包封效率,并因其优异的光热转换能力而有助于产生协同光热效应。此外,PVA在微针刺入皮肤后可迅速溶解并快速释放抗炎解毒的Pae,营造有利的低酸皮下环境。响应pH变化和近红外效应,TP从P - MXene中持续释放并通过水凝胶的肿胀孔隙递送。基于这些特性,我们证明这些微针可有效降低促纤维化关键细胞因子白细胞介素 - 1β和转化生长因子 - β,从而减少胶原蛋白沉积并降低表皮厚度,改善硬皮病小鼠模型中的皮肤纤维化和毛细血管病变。这些发现突出了这些微针在皮肤病治疗中的重要临床潜力。
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