用于治疗糖尿病足溃疡混合细菌-真菌感染的含药多靶点海藻酸盐敷料。

Medicated multi-targeted alginate-based dressings for potential treatment of mixed bacterial-fungal infections in diabetic foot ulcers.

机构信息

School of Science, Faculty of Engineering and Science, University of Greenwich, Medway, Central Ave., Chatham Maritime, Kent ME4 4TB, UK.

出版信息

Int J Pharm. 2021 Sep 5;606:120903. doi: 10.1016/j.ijpharm.2021.120903. Epub 2021 Jul 19.

DOI:10.1016/j.ijpharm.2021.120903

PMID:34293470

Abstract

Recently developed medicated dressings target either bacterial or fungal infection only, which is not effective for the treatment of mixed infections common in diabetic foot ulcers (DFUs). This study aimed to develop advanced bioactive alginate-based dressings (films and wafers) to deliver therapeutically relevant doses of ciprofloxacin (CIP) and fluconazole (FLU) to target mixed bacterial and fungal infections in DFUs. The alginate compatibility with the drugs was confirmed by SEM, XRD, FTIR and texture analysis, while the medicated wafers showed better fluid handling properties than the films in the presence of simulated wound fluid. The dressings showed initial fast release of FLU followed by sustained release of CIP which completely eradicated E. coli, S. aureus, P. aeruginosa and reduced fungal load (C. albicans) by 10-fold within 24 h. Moreover, the medicated dressings were biocompatible (>70% cell viability over 72 h) with human primary adult keratinocytes and in-vitro scratch assay showed 65-68% wound closure within 7 days.

摘要

最近开发的药用敷料仅针对细菌或真菌感染，对于治疗糖尿病足溃疡（DFU）中常见的混合感染效果不佳。本研究旨在开发先进的基于海藻酸盐的敷料（薄膜和薄片），以将治疗相关剂量的环丙沙星（CIP）和氟康唑（FLU）递送至 DFU 中的混合细菌和真菌感染部位。SEM、XRD、FTIR 和质地分析证实了海藻酸盐与药物的相容性，而与模拟伤口液一起时，载药薄片的流体处理性能优于薄膜。敷料显示出 FLU 的初始快速释放，随后是 CIP 的持续释放，在 24 小时内完全消除了大肠杆菌、金黄色葡萄球菌、铜绿假单胞菌，并将真菌负荷（白色念珠菌）降低了 10 倍。此外，载药敷料与人原代成人生发角质细胞具有生物相容性（72 小时内超过 70%的细胞活力），体外划痕试验显示 7 天内伤口闭合率为 65-68%。