Nitric oxide-releasing chitosan oligosaccharides as antibacterial agents

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• 作者：Yuan Lu ; Danielle L. Slomberg ; Mark H. Schoenfisch
• 关键词：Drug release ; Nitric oxide ; Chitosan ; Antibacterial ; Biodegradable
• 刊名：Biomaterials
• 出版年：February, 2014
• 年：2014
• 卷：35
• 期：5
• 页码：1716-1724
• 全文大小：1189 K

文摘

Secondary amine-functionalized chitosan oligosaccharides of different molecular weights (i.e., 鈭?500, 5000, 10,000) were synthesized by grafting 2-methyl aziridine from the primary amines on chitosan oligosaccharides, followed by reaction with nitric oxide (NO) gas under basic conditions to yield N-diazeniumdiolate NO donors. The total NO storage, maximum NO flux, and half-life of the resulting NO-releasing chitosan oligosaccharides were controlled by the molar ratio of 2-methyl aziridine to primary amines (e.g., 1:1, 2:1) and the functional group surrounding the N-diazeniumdiolates (e.g., polyethylene glycol (PEG) chains), respectively. The secondary amine-modified chitosan oligosaccharides greatly increased the NO payload over existing biodegradable macromolecular NO donors. In addition, the water-solubility of the chitosan oligosaccharides enabled their penetration across the extracellular polysaccharides matrix of Pseudomonas aeruginosa biofilms and association with embedded bacteria. The effectiveness of these chitosan oligosaccharides at biofilm eradication was shown to depend on both the molecular weight and ionic characteristics. Low molecular weight and cationic chitosan oligosaccharides exhibited rapid association with bacteria throughout the entire biofilm, leading to enhanced biofilm killing. At concentrations resulting in 5-log killing of bacteria in Pseudomonas aeruginosa (P. aeruginosa) biofilms, the NO-releasing and control chitosan oligosaccharides elicited no significant cytotoxicity to mouse fibroblast L929 cells in聽vitro.