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含抗生物膜和抗菌剂的水凝胶有益于与生物膜相关的伤口感染:配方特性和体外研究。

Hydrogels Containing Antibiofilm and Antimicrobial Agents Beneficial for Biofilm-Associated Wound Infection: Formulation Characterizations and In vitro Study.

机构信息

Center for Drug Delivery Research, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia.

出版信息

AAPS PharmSciTech. 2018 Apr;19(3):1219-1230. doi: 10.1208/s12249-017-0937-4. Epub 2017 Dec 26.

Abstract

Bacterial biofilm which adheres onto wound surface is shown to be impervious to antibiotics and this in turn delays wound healing. Previous studies showed that antibiofilm agents such as xylitol and ethylenediaminetetraacetic acid (EDTA) prevent bacterial adherence onto surfaces. Formulation of a wound dressing containing antibiofilm agents may be a plausible strategy in breaking the biofilm on wound surfaces and at the same time increase the efficacy of the antibiotic. The purpose of this study was to develop hydrogel formulations containing antibiofilm agents along with antibiotic (gentamicin) for bacterial biofilm-associated wound infection. Sodium carboxymethyl cellulose (NaCMC) hydrogels loaded with antibiofilm agents and antibiotic were prepared. The hydrogels were characterized for their physical properties, rheology, Fourier transform infrared spectroscopy (FTIR), drug content uniformity, differential scanning calorimetry (DSC) and in vitro drug release study. The antibiofilm (Crystal Violet staining and XTT assay) and antibacterial performances of the hydrogels against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli were assessed in vitro. The formulated hydrogels showed adequate release of both antibiofilm agents (xylitol and EDTA). Both antimicrobial and antibiofilm tests showed promising results and demonstrated that the combination of xylitol, EDTA, and gentamicin had an additive effect against both Gram-positive and Gram-negative bacteria. In summary, NaCMC (sodium carboxymethyl cellulose) hydrogels containing the combination of antimicrobial and antibiofilm agents were successfully developed and this can be a new strategy in combating biofilm in wound infection which in turn accelerate wound healing.

摘要

细菌生物膜会黏附在伤口表面,使其对抗生素具有抗药性,从而导致伤口愈合延迟。先前的研究表明,木糖醇和乙二胺四乙酸(EDTA)等抗生物膜剂可防止细菌黏附在表面。在伤口敷料中加入抗生物膜剂可能是打破伤口表面生物膜的一种合理策略,同时提高抗生素的疗效。本研究旨在开发含有抗生物膜剂(包括抗生素庆大霉素)的水凝胶制剂,用于治疗细菌生物膜相关的伤口感染。制备了负载有抗生物膜剂和抗生素的羧甲基纤维素钠(NaCMC)水凝胶。对水凝胶的物理性质、流变学、傅里叶变换红外光谱(FTIR)、药物含量均匀性、差示扫描量热法(DSC)和体外药物释放进行了表征。评估了水凝胶对金黄色葡萄球菌、枯草芽孢杆菌、铜绿假单胞菌和大肠杆菌的抗生物膜(结晶紫染色和 XTT 测定)和抗菌性能。所制备的水凝胶能充分释放两种抗生物膜剂(木糖醇和 EDTA)。抗菌和抗生物膜试验均取得了良好的效果,表明木糖醇、EDTA 和庆大霉素的组合对革兰氏阳性菌和革兰氏阴性菌均具有协同作用。综上所述,成功开发了含有抗菌和抗生物膜剂的 NaCMC(羧甲基纤维素钠)水凝胶,这可能是一种对抗伤口感染生物膜的新策略,从而加速伤口愈合。

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