Quaternized Polysaccharide-Based Cationic Micelles as a Macromolecular Approach to Eradicate Multidrug-Resistant...

Area of Science:

• Materials Science
• Biotechnology
• Medicinal Chemistry

Background:

• Rising antimicrobial resistance necessitates novel therapeutic agents.
• Quaternized polysaccharides are promising antimicrobial candidates, but synthesis and resistance mechanisms require further investigation.

Purpose of the Study:

• To synthesize quaternized chitin (QC) and quaternized chitosan (QCS) derivatives using a green KOH/urea system.
• To investigate the structure-activity relationship and biological efficacy of these derivatives in vitro and in vivo.
• To identify an optimized derivative for antimicrobial applications and wound healing.

Main Methods:

• Homogeneous synthesis of QC and QCS derivatives via a green KOH/urea system.
• Evaluation of structure-activity relationships by varying degree of quaternization (DQ) and degree of deacetylation (DD').
• In vitro and in vivo assays for antimicrobial activity, cytotoxicity, biofilm inhibition, hemocompatibility, and wound healing efficacy.

Main Results:

• A balanced DQ and DD' is crucial for optimizing antimicrobial properties and minimizing cytotoxicity.
• QCS-2 (DQ=0.46, DD'=82%) demonstrated broad-spectrum antimicrobial activity, good hemocompatibility, and excellent cytocompatibility.
• QCS-2 effectively inhibited and eradicated bacterial biofilms, showed low drug resistance potential, and exhibited significant in vivo anti-MRSA effects, promoting wound healing.

Conclusions:

• The KOH/urea system provides an effective green route for synthesizing QC and QCS derivatives.
• Optimized QCS derivatives offer a promising platform for developing new antimicrobial agents with enhanced efficacy and safety.
• QCS-2 presents significant potential for treating infections and accelerating wound healing, comparable to existing therapies.