Chitosan is a cationic polymer of natural origin and has been widely explored as a pharmaceutical excipient for a broad\r\nrange of biomedical applications. While generally considered safe and biocompatible, chitosan has the ability to induce\r\ninflammatory reactions, which varies with the physical and chemical properties. We hypothesized that the previously\r\nreported zwitterionic chitosan (ZWC) derivative had relatively low pro-inflammatory potential because of the aqueous\r\nsolubility and reduced amine content. To test this, we compared various chitosans with different aqueous solubilities or\r\nprimary amine contents with respect to the intraperitoneal (IP) biocompatibility and the propensity to induce proinflammatory\r\ncytokine production from macrophages. ZWC was relatively well tolerated in ICR mice after IP administration\r\nand had no pro-inflammatory effect on nai�¨ve macrophages. Comparison with other chitosans indicates that these\r\nproperties are mainly due to the aqueous solubility at neutral pH and relatively low molecular weight of ZWC. Interestingly,\r\nZWC had a unique ability to suppress cytokine/chemokine production in macrophages challenged with lipopolysaccharide\r\n(LPS). This effect is likely due to the strong affinity of ZWC to LPS, which inactivates the pro-inflammatory function of LPS,\r\nand appears to be related to the reduced amine content. Our finding warrants further investigation of ZWC as a functional\r\nbiomaterial.
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