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葡萄糖响应型自修复双层药物微针通过木马策略促进糖尿病伤口愈合。

Glucose-Responsive Self-Healing Bilayer Drug Microneedles Promote Diabetic Wound Healing Via a Trojan-Horse Strategy.

机构信息

Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, 763 Heguang Road, Changchun 130021, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2024 May 15;16(19):24351-24371. doi: 10.1021/acsami.4c03050. Epub 2024 May 1.

DOI:10.1021/acsami.4c03050
PMID:38690969
Abstract

Chronic nonhealing wounds are serious complications of diabetes with a high morbidity, and they can lead to disability or death. Conventional drug therapy is ineffective for diabetic wound healing because of the complex environment of diabetic wounds and the depth of drug penetration. Here, we developed a self-healing, dual-layer, drug-carrying microneedle (SDDMN) for diabetic wound healing. This SDDMN can realize transdermal drug delivery and broad-spectrum sterilization without drug resistance and meets the multiple needs of the diabetic wound healing process. Quaternary ammonium chitosan cografted with dihydrocaffeic acid (Da) and l-arginine and oxidized hyaluronic acid-dopamine are the main parts of the self-healing hydrogel patch. Methacrylated poly(vinyl alcohol) (methacrylated PVA) and phenylboronic acid (PBA) were used as the main part of the MN, and gallium porphyrin modified with 3-amino-1,2 propanediol (POGa) and insulin were encapsulated at its tip. Under hyperglycaemic conditions, the PBA moiety in the MN reversibly formed a glucose-boronic acid complex that promoted the rapid release of POGa and insulin. POGa is disguised as hemoglobin through a Trojan-horse strategy, which is then taken up by bacteria, allowing it to target bacteria and infected lesions. Based on the synergistic properties of these components, SDDMN-POGa patches exhibited an excellent biocompatibility, slow drug release, and antimicrobial properties. Thus, these patches provide a potential therapeutic approach for the treatment of diabetic wounds.

摘要

慢性难愈性创面是糖尿病的严重并发症,发病率高,可导致残疾或死亡。由于糖尿病创面的复杂环境和药物渗透深度,传统的药物治疗对糖尿病创面愈合无效。在这里,我们开发了一种用于糖尿病创面愈合的自修复、双层、载药微针(SDDMN)。这种 SDDMN 可以实现经皮药物输送和广谱杀菌,无耐药性,满足糖尿病创面愈合过程的多种需求。季铵化壳聚糖与二氢咖啡酸(Da)和 l-精氨酸共聚,并氧化透明质酸-多巴胺是自修复水凝胶贴片的主要部分。甲基丙烯酰化聚乙烯醇(甲基丙烯酰化 PVA)和苯硼酸(PBA)被用作 MN 的主要部分,其尖端包封了 3-氨基-1,2-丙二醇修饰的卟啉(POGa)和胰岛素。在高血糖条件下,MN 中的 PBA 部分可逆地形成葡萄糖-硼酸复合物,促进 POGa 和胰岛素的快速释放。POGa 通过特洛伊木马策略伪装成血红蛋白,然后被细菌摄取,使其能够靶向细菌和感染部位。基于这些成分的协同特性,SDDMN-POGa 贴片表现出优异的生物相容性、缓慢的药物释放和抗菌性能。因此,这些贴片为治疗糖尿病创面提供了一种潜在的治疗方法。

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