S-Nitrosothiol-modified nitric oxide-releasing chitosan oligosaccharides as antibacterial agents. (15th January 2015)

• Record Type: Journal Article
• Authors: Lu, Yuan; Shah, Anand; Hunter, Rebecca A.; Soto, Robert J.; Schoenfisch, Mark H.
• Is Part Of: Acta biomaterialia. Volume 12(2015)
• Page Start: 62
• Page End: 69
• Publication Date: 2015-01-15
• Subjects: S-Nitrosothiol -- Nitric oxide -- Chitosan -- Ascorbic acid -- Synergy; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2014.10.028
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: S -Nitrosothiol-modified chitosan oligosaccharides were synthesized by reaction with 2-iminothiolane hydrochloride and 3-acetamido-4, 4-dimethylthietan-2-one, followed by thiol nitrosation. The resulting nitric oxide (NO)-releasing chitosan oligosaccharides stored ∼0.3 μmol NO mg −1 chitosan. Both the chemical structure of the nitrosothiol (i.e. primary and tertiary) and the use of ascorbic acid as a trigger for NO donor decomposition were used to control the NO-release kinetics. With ascorbic acid, the S -nitrosothiol-modified chitosan oligosaccharides elicited a 4-log reduction in Pseudomonas aeruginosa viability. Confocal microscopy indicated that the primary S -nitrosothiol-modified chitosan oligosaccharides associated more with the bacteria relative to the tertiary S -nitrosothiol system. The primary S -nitrosothiol-modified chitosan oligosaccharides elicited minimal toxicity towards L929 mouse fibroblast cells at the concentration necessary for a 4-log reduction in bacterial viability, further demonstrating the potential of S -nitrosothiol-modified chitosan oligosaccharides as NO-release therapeutics.