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一种负载壳聚糖/岩藻依聚糖纳米颗粒的普鲁兰多糖微针贴片,用于差异药物释放以促进伤口愈合。

A chitosan/fucoidan nanoparticle-loaded pullulan microneedle patch for differential drug release to promote wound healing.

作者信息

Younas Ayesha, Dong Zhuolin, Hou Ziye, Asad Muhammad, Li Mengru, Zhang Nan

机构信息

Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, PR China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou 450001, Henan, PR China.

Green Catalysis Center and College of Chemistry, Zhengzhou University, Zhengzhou 450001, PR China.

出版信息

Carbohydr Polym. 2023 Apr 15;306:120593. doi: 10.1016/j.carbpol.2023.120593. Epub 2023 Jan 23.

DOI:10.1016/j.carbpol.2023.120593
PMID:36746584
Abstract

Wound healing is a largely unmet medical issue in trauma, burn, and diabetes. In this study, a pullulan-based and nanoparticle-loaded smart microneedle patch is designed to release drugs differentially based on the needs of wound healing. Chitosan and fucoidan are first used to prepare moxifloxacin (MOX)-loaded nanoparticles (MOXNPs) with a diameter of 258.0 ± 10.86 nm, PDI 0.19 ± 0.06, and surface charge 45.1 ± 3.9 mV. MOXNPs, lidocaine (LH), and thrombin (TH) are then incorporated to a 30 % (w/w) pullulan-based microneedle patch (TH + LH + MOXNPs@MN). TH + LH + MOXNPs@MN possesses uniform and cone-shaped microneedles with a length of 725 μm, demonstrating good biocompatibility, sufficient strength for skin penetration, fast skin dissolution within 55 ± 5 min, rapid release of TH and LH within 1 h, and sustained release of MOX for 24 h. TH + LH + MOXNPs@MN heals mice skin wounds completely within 7 days and restores collagen deposition with accelerated cell proliferation, granulation, and reduced pro-inflammatory cytokines. In conclusion, this study utilizes combined polysaccharides to develop a smart multifunctional microneedle platform that achieves rapid hemostasis/analgesia and sustained bactericidal action. The smart and combined therapy is a potential strategy for high-quality wound healing.

摘要

伤口愈合在创伤、烧伤和糖尿病领域是一个很大程度上未得到解决的医学问题。在本研究中,设计了一种基于普鲁兰多糖且负载纳米颗粒的智能微针贴片,以根据伤口愈合的需求差异释放药物。首先使用壳聚糖和岩藻依聚糖制备直径为258.0 ± 10.86 nm、多分散指数(PDI)为0.19 ± 0.06且表面电荷为45.1 ± 3.9 mV的载莫西沙星(MOX)纳米颗粒(MOXNPs)。然后将MOXNPs、利多卡因(LH)和凝血酶(TH)掺入30%(w/w)的基于普鲁兰多糖的微针贴片中(TH + LH + MOXNPs@MN)。TH + LH + MOXNPs@MN具有长度为725 μm的均匀锥形微针,表现出良好的生物相容性、足够的皮肤穿透强度、在55 ± 5分钟内快速皮肤溶解、在1小时内快速释放TH和LH以及MOX持续释放24小时。TH + LH + MOXNPs@MN在7天内完全愈合小鼠皮肤伤口,并通过加速细胞增殖、肉芽形成和减少促炎细胞因子来恢复胶原蛋白沉积。总之,本研究利用复合多糖开发了一个智能多功能微针平台,该平台实现了快速止血/镇痛和持续杀菌作用。这种智能联合疗法是高质量伤口愈合的一种潜在策略。

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