Quaternized Polysaccharide-Based Cationic Micelles as a Macromolecular Approach to Eradicate Multidrug-Resistant Bacterial Infections while Mitigating Antimicrobial Resistance.

Microbial infections and microbial resistance lead to a high demand for new antimicrobial agents. Quaternized polysaccharides are cationic antimicrobial candidates; however, the limitation of homogeneous synthesis solvents that affect the molecular structure and biological activities, as well as their drug resistance remains unclear. Therefore, the authors homogeneously synthesize a series of quaternized chitin (QC) and quaternized chitosan (QCS) derivatives via a green and effective KOH/urea system and investigate their structure-activity relationship and biological activity in vivo and in vitro. Their study reveals that a proper match of degree of quaternization (DQ) and degree of deacetylation (DD') of QC or QCS is key to balance antimicrobial property and cytotoxicity. They identify QCS-2 as the optimized antimicrobial agent with a DQ of 0.46 and DD' of 82%, which exhibits effective broad-spectrum antimicrobial properties, good hemocompatibility, excellent cytocompatibility, and effective inhibition of bacterial biofilm formation and eradication of mature bacterial biofilms. Moreover, QCS-2 exhibits a low propensity for development of drug resistance and significant anti-infective effects on MRSA in vivo comparable to that of vancomycin, avoiding excessive inflammation and promoting the formation of new blood vessels, hair follicles, and collagen deposition to thus expedite wound healing.