College of Pharmaceutical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, China; State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Clinical Research Institute, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310014, China.
Biomaterials. 2025 Jan;312:122742. doi: 10.1016/j.biomaterials.2024.122742. Epub 2024 Jul 31.
Hypertrophic scar (HS) tends to raised above skin level with high inflammatory microenvironment and excessive proliferation of myofibroblasts. The HS therapy remains challenging due to dense scar tissue which makes it hard to penetrate, and the side effects resulting from intralesional corticosteroid injection which is the mainstay treatment in clinic. Herein, bilayer microneedle patches combined with dexamethasone and colchicine (DC-MNs) with differential dual-release pattern is designed. Two drugs loaded in commercially available materials HA and PLGA, respectively. Specifically, after administration, outer layer rapidly releases the anti-inflammatory drug dexamethasone, which inhibits macrophage polarization to pro-inflammatory phenotype in scar tissue. Subsequently, inner layer degrades sustainedly, releasing antimicrotubular agent colchicine, which suppresses the overproliferation of myofibroblasts with extremely narrow therapeutic window, and inhibits the overexpression of collagen, as well as promotes the regular arrangement of collagen. Only applied once, DC-MNs directly delivered drugs to the scar tissue. Compared to traditional treatment regimen, DC-MNs significantly suppressed HS at lower dosage and frequency by differential dual-release design. Therefore, this study put forward the idea of integrated DC-MNs accompany the development of HS, providing a non-invasive, self-applicable, more efficient and secure strategy for treatment of HS.
增生性瘢痕(HS)往往高于皮肤表面,具有高炎症微环境和过度增殖的肌成纤维细胞。由于瘢痕组织致密,难以穿透,以及临床主要治疗方法——腔内皮质类固醇注射的副作用,HS 的治疗仍然具有挑战性。在此,设计了一种具有差异化双重释放模式的双层微针贴片联合地塞米松和秋水仙碱(DC-MNs)。两种药物分别装载在市售的透明质酸(HA)和聚乳酸-羟基乙酸共聚物(PLGA)材料中。具体来说,给药后,外层迅速释放抗炎药物地塞米松,抑制瘢痕组织中巨噬细胞向促炎表型极化。随后,内层持续降解,释放微管抑制药物秋水仙碱,抑制肌成纤维细胞的过度增殖,其治疗窗极窄,抑制胶原的过度表达,并促进胶原的规则排列。DC-MNs 只需应用一次,即可将药物直接递送至瘢痕组织。与传统治疗方案相比,DC-MNs 通过差异化双重释放设计以更低的剂量和频率显著抑制 HS。因此,本研究提出了将 DC-MNs 与 HS 的发展相结合的理念,为 HS 的治疗提供了一种非侵入性、自我应用、更高效和安全的策略。
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