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载有基质金属蛋白酶抑制剂药物的 RGD 肽接枝聚己二酸丁二醇酯-对苯二甲酸酯/明胶电纺纳米纤维缓解伤口:一项研究。

RGD peptide grafted polybutylene adipate--terephthalate/gelatin electrospun nanofibers loaded with a matrix metalloproteinase inhibitor drug for alleviating of wounds: an / study.

机构信息

Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Drug Dev Ind Pharm. 2020 Mar;46(3):484-497. doi: 10.1080/03639045.2020.1730397. Epub 2020 Mar 3.

Abstract

The objective of the present study was the fabrication of a wound dressing membrane based on RGD modified polybutylene adipate--terephthalate (PBAT)/gelatin nanofibrous structures loaded with doxycycline (DOX). This type of nanofiber for wound healing has not been reported so far and is quite novel. PBAT and gelatin nanofibers were separately electrospun using double needles electrospinning setup. Electrospinning variables were optimized to obtain bead-free thin nanofibers. The amount of drug loaded and release were measured in different concentrations of DOX and PBAT. MMPs inhibition was studied by polyacrylamide gel-zymography. Then, surface of the nanofibers was modified with RGD peptide, and their antimicrobial effect was investigated on and . Effect of developed nanofibrous membranes on L929 fibroblast cells proliferation, adhesion and closure of excised wounds in rat were also studied. PBAT/gelatin nanofibrous structures with average fiber diameter of 75-529 nm were developed successfully. Drug release study revealed that about 65% of DOX was released from the optimized formulation (PD) after 20 h. The developed DOX loaded membrane inhibited the MMPs activity and showed no cytotoxicity. RGD surface-modified PBAT/gelatin nanofibers significantly improved the wound closure and histopathological results (re-epithelialization, collagen deposition, and angiogenesis) in rats compared to the control groups. Overall, RGD immobilized PBAT/gelatin nanofibrous membrane may have a potential application for wound healing.

摘要

本研究的目的是制备一种基于 RGD 修饰的聚丁二酸丁二醇酯-对苯二甲酸酯(PBAT)/明胶纳米纤维结构负载多西环素(DOX)的伤口敷料膜。到目前为止,还没有报道过这种用于伤口愈合的纳米纤维,它是非常新颖的。使用双针静电纺丝装置分别将 PBAT 和明胶电纺成纳米纤维。优化静电纺丝参数以获得无珠的细纳米纤维。在不同浓度的 DOX 和 PBAT 下测量载药量和释放量。通过聚丙烯酰胺凝胶-酶谱法研究 MMPs 抑制作用。然后,用 RGD 肽修饰纳米纤维的表面,并研究其对 和 的抗菌效果。还研究了开发的纳米纤维膜对 L929 成纤维细胞增殖、细胞黏附和大鼠切口闭合的影响。成功制备了平均纤维直径为 75-529nm 的 PBAT/明胶纳米纤维结构。药物释放研究表明,优化配方(PD)在 20 小时后释放了约 65%的 DOX。开发的负载 DOX 的膜抑制了 MMPs 的活性,且无细胞毒性。与对照组相比,RGD 固定化 PBAT/明胶纳米纤维显著改善了大鼠的伤口闭合和组织病理学结果(上皮再形成、胶原沉积和血管生成)。总体而言,RGD 固定化 PBAT/明胶纳米纤维膜在伤口愈合方面可能具有潜在的应用前景。

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