Low and high molecular weight alginate biopolymers were chemically modified to store and release potentially therapeutic levels of nitric oxide (NO). Carbodiimide chemistry was first used to modify carboxylic acid functional groups with a series of small molecule alkyl amines. The resulting secondary amines were subsequently converted to N-diazeniumdiolate NO donors via reaction with NO gas under basic conditions. NO donor-modified alginates stored between 0.4–0.6 μmol NO·mg^–1. In aqueous solution, the NO-release kinetics were diverse (0.3–13 h half-lives), dependent on the precursor amine structure. The liberated NO showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus with pathogen eradication efficiency dependent on both molecular weight and NO-release kinetics. The combination of lower molecular weight (∼5 kDa) alginates with moderate NO-release durations (half-life of ∼4 h) resulted in enhanced killing of both planktonic and biofilm-based bacteria. Toxicity against human respiratory epithelial (A549) cells proved negligible at NO-releasing alginate concentrations required to achieve a 5-log reduction in viability in the biofilm eradication assay.

中文翻译：

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释放一氧化氮的藻酸盐

低分子量和高分子量藻酸盐生物聚合物经过化学修饰，可储存和释放潜在治疗水平的一氧化氮 (NO)。碳二亚胺化学首先用一系列小分子烷基胺来修饰羧酸官能团。所得仲胺随后通过在碱性条件下与NO气体反应转化为N-二醇二氮烯鎓NO供体。NO 供体修饰的藻酸盐储存在 0.4–0.6 μmol NO·mg ^–1之间。在水溶液中，NO 释放动力学各不相同（半衰期为 0.3-13 小时），具体取决于前体胺结构。释放的 NO 对铜绿假单胞菌和金黄色葡萄球菌具有杀菌活性，其病原体根除效率取决于分子量和 NO 释放动力学。较低分子量（~5 kDa）藻酸盐与中等 NO 释放持续时间（半衰期~4 小时）的组合可增强对浮游细菌和生物膜细菌的杀灭作用。事实证明，在生物膜根除测定中，在释放 NO 的藻酸盐浓度下，实现存活率降低 5 个对数级，对人呼吸道上皮 (A549) 细胞的毒性可以忽略不计。