Anti-biofilm activity of chitosan gels formulated with silver nanoparticles and their cytotoxic effect on human fibroblasts
Anti-biofilm activity of chitosan gels formulated with silver nanoparticles and their cytotoxic effect on human fibroblasts
复制标题
DOI：
10.1016/j.msec.2015.11.036
复制
发表时间：
2016-03-01
影响因子：
7.9
通讯作者：
Martinez-Gutierrez, F.
中科院分区：
文献类型：
--
作者：
Perez-Diaz, M.;Alvarado-Gomez, E.;Martinez-Gutierrez, F.
慢性创面多菌种生物膜的形成是一个严重的健康问题，主要产生对抗菌素治疗的强烈耐药机制。纳米银(AgNPs)作为广谱抗菌剂的应用已有研究。然而，它们的细胞毒性作用限制了它在医学领域的使用。本研究的目的是以磺胺嘧啶银(SSD)为标准药物，评价载银纳米粒壳聚糖凝胶制剂对临床分离菌株的抗生物被膜能力以及对人原代成纤维细胞的细胞毒作用。在模拟人体皮肤营养物质流动的条件下，使用标准滴流反应器(DFR)对从慢性创面感染患者体内获得的金黄色葡萄球菌、苯唑西林耐药(MRSA)和铜绿假单胞菌多菌种生物膜进行了研究。当壳聚糖凝胶与AgNPs的浓度为100ppm时，壳聚糖凝胶和SSD对MRSA的抑菌率均为6.0，而添加AgNPs的壳聚糖凝胶的抗菌活性需增加到1000ppm才能达到3.3的对数减少率，而SSD对两种细菌的抑制率与阴性对照相比均有所降低。对原代成纤维细胞的生物相容性评价表明，含银纳米粒的壳聚糖凝胶即使在高浓度下也能获得更好的生物相容性，而SSD则能杀死所有的原代成纤维细胞。综上所述，载银壳聚糖凝胶制剂能有效地防止生物膜的形成，杀灭已建立的生物膜中的细菌，提示载银壳聚糖凝胶可用于慢性创面感染的预防和治疗。载银纳米粒的壳聚糖凝胶制剂的生物相容性具有统计学意义，这是一个进步；然而，要将这项技术转化为治疗和预防策略，还需要进一步的研究和开发。(C)2015爱思唯尔B.V.保留所有权利。
The development of multi-species biofilms in chronic wounds is a serious health problem that primarily generates strong resistance mechanisms to antimicrobial therapy. The use of silver nanoparticles (AgNPs) as a broadspectrum antimicrobial agent has been studied previously. However, their cytotoxic effects limit its use within the medical area. The purpose of this study was to evaluate the anti-biofilm capacity of chitosan gel formulations loaded with AgNPs, using silver sulfadiazine (SSD) as a standard treatment, on strains of clinical isolates, as well as their cytotoxic effect on human primary fibroblasts. Multi-species biofilm of Staphylococcus aureus oxacillin resistant (MRSA) and Pseudomonas aeruginosa obtained from a patient with chronic wound infection were carried out using a standard Drip Flow Reactor (DFR) under conditions that mimic the flow of nutrients in the human skin. Anti-biofilm activity of chitosan gels and SSD showed a log-reduction of 6.0 for MRSA when chitosan gel with AgNPs at a concentration of 100 ppm was used, however it was necessary to increase the concentration of the chitosan gel with AgNPs to 1000 ppm to get a log-reduction of 3.3, while the SSD showed a total reduction of both bacteria in comparison with the negative control. The biocompatibility evaluation on primary fibroblasts showed better results when the chitosan gels with AgNPs were tested even in the high concentration, in contrast with SSD, which killed all the primary fibroblasts. In conclusion, chitosan gel formulations loaded with AgNPs effectively prevent the formation of biofilm and kill bacteria in established biofilm, which suggest that chitosan gels with AgNPs could be used for prevention and treatment of infections in chronic wounds. The statistic significance of the biocompatibility of chitosan gel formulations loaded with AgNPs represents an advance; however further research and development are necessary to translate this technology into therapeutic and preventive strategies. (C) 2015 Elsevier B.V. All rights reserved.