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一种易于使用的抗菌水凝胶能有效杀灭细菌、真菌和流感病毒。

An easy-to-use antimicrobial hydrogel effectively kills bacteria, fungi, and influenza virus.

作者信息

Bhattacharjee Brinta, Jolly Logia, Mukherjee Riya, Haldar Jayanta

机构信息

Antimicrobial Research Laboratory, New Chemistry Unit, Jakkur, Bengaluru 560064, Karnataka, India.

Antimicrobial Research Laboratory, School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Jakkur, Bengaluru 560064, Karnataka, India.

出版信息

Biomater Sci. 2022 Apr 12;10(8):2014-2028. doi: 10.1039/d2bm00134a.

Abstract

Various drug resistant pathogens such as bacteria, fungi and viruses enter a host through different routes, which can lead to health-related problems and even fatalities. Propagation of these infectious microbes majorly occurs through the mucosal openings or upon topical contact. To curb their transmission or to cure infections associated with these pathogens, herein we describe the development of an antimicrobial hydrogel, based on a water soluble quaternary lipophilic polyethyleneimine derivative (QPEINH-C). The cationic polymer QPEINH-C exhibited antibacterial activity against drug-resistant Gram-positive bacteria (MIC = 10-62 μg mL) and Gram-negative bacteria (MIC = 117-123 μg mL). The derivative showed killing of human pathogenic fungi (MIC = 58-67 μg mL), including their clinical isolates. The rapid bactericidal and fungicidal nature were confirmed from the fast inactivation kinetics of bacterial cells (methicillin resistant and vancomycin resistant ) within 3-6 hours and within 1 h with ∼5-6 log reduction in the microbial burden. This antibacterial and antifungal cationic polymer was then used to construct an antimicrobial shear-thinning hydrogel (Bacfuvir), through non-covalent crosslinking with biocompatible gellan and polyvinyl alcohol (PVA). This hydrogel displayed ∼5-7 log reduction of numerous multidrug-resistant bacteria and their stationary phase cells which are insusceptible to conventional antibiotics. In addition, >99.9 % viable bacterial burden was reduced from preformed biofilm matrices of drug-resistant bacteria. Alongside, fluconazole-resistant strains were killed completely within 15-60 min upon exposure to Bacfuvir gel. Most importantly, MRSA and cells were reduced (3-4 log) in polymicrobial biofilms after hydrogel treatment. The hydrogel exhibited 99.9 % reduction of influenza viruses in a rapid manner. Due to the biocompatibility of Bacfuvir gel on topical application in a murine model and easy administration owing to its shear-thinning behaviour, this hydrogel can markedly contribute to mitigating drug-resistant bacterial, fungal and viral infections in healthcare settings.

摘要

各种耐药病原体,如细菌、真菌和病毒,通过不同途径进入宿主,这可能导致与健康相关的问题甚至死亡。这些传染性微生物主要通过粘膜开口或局部接触进行传播。为了抑制它们的传播或治愈与这些病原体相关的感染,在此我们描述了一种基于水溶性季铵化亲脂性聚乙烯亚胺衍生物(QPEINH-C)的抗菌水凝胶的开发。阳离子聚合物QPEINH-C对耐药革兰氏阳性菌(MIC = 10 - 62 μg/mL)和革兰氏阴性菌(MIC = 117 - 123 μg/mL)表现出抗菌活性。该衍生物对包括临床分离株在内的人类致病真菌(MIC = 58 - 67 μg/mL)具有杀灭作用。从细菌细胞(耐甲氧西林和耐万古霉素)在3 - 6小时内的快速失活动力学以及在1小时内微生物负荷降低约5 - 6个对数级,证实了其快速杀菌和杀真菌特性。然后,这种抗菌和抗真菌阳离子聚合物通过与生物相容性结冷胶和聚乙烯醇(PVA)进行非共价交联,用于构建抗菌剪切变稀水凝胶(Bacfuvir)。这种水凝胶对许多多重耐药细菌及其对传统抗生素不敏感的稳定期细胞显示出约5 - 7个对数级的减少。此外,耐药细菌预先形成的生物膜基质中>99.9%的活菌负荷降低。同时,耐氟康唑菌株在接触Bacfuvir凝胶后15 - 60分钟内被完全杀灭。最重要的是,水凝胶处理后,多微生物生物膜中的耐甲氧西林金黄色葡萄球菌和 细胞减少了(3 - 4个对数级)。该水凝胶能快速使流感病毒减少99.9%。由于Bacfuvir凝胶在小鼠模型局部应用时具有生物相容性,且因其剪切变稀行为易于给药,这种水凝胶可显著有助于减轻医疗环境中耐药细菌、真菌和病毒感染。

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