The extensive use/misuse of antibiotics is a key factor for the rapid rise and global spread of multidrug-resistant (MDR) pathogens, which now pose a major threat to public health. This situation necessitates the development of innovative, biocompatible, and sustainable antimicrobial materials capable of overcoming the limitations of traditional drug-based therapies. Chitosan (CS), a cationic polymer, is an excellent candidate for various medical applications; however, its antimicrobial activity alone may be insufficient against broad-spectrum pathogens. Therefore, in this study, CS-ZnS nanocomposite hydrogel beads were successfully synthesized that demonstrated excellent antibacterial, anti-biofilm properties, as well as suppression of metabolic activity against both Gram-positive and Gram-negative MDR bacterial pathogens. In addition, the hydrogel beads showed significant antioxidant property and demonstrated hemocompatibility. The morphology of this composite was characterized using SEM and TEM, revealing Zinc sulfide (ZnS) nanoflakes sized 8 to 10 nm. The structural properties were evaluated using XRD, Raman, and FTIR spectroscopy. The findings of this study were further supported by in silico analysis, which demonstrated strong interactions with target proteins, including MecA in Staphylococcus aureus and oxacillin-hydrolyzing class D β-lactamase in Pseudomonas aeruginosa. This CS-ZnS system represents a novel, sustainable, and cost-effective biotherapeutic material with potential applications in combating MDR pathogens.
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