Preparation and Physicochemical Characterization of Chitosan-Coated Iron Oxide Nanoparticles Conjugated with Oxacillin: Antimicrobial, Antibiofilm, and Biocompatibility Activities against MRSA Staphylococcus aureus

The growing threat of antimicrobial resistance and biofilm-associated infections has critically undermined the efficacy of conventional antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) represents a clinically significant multidrug-resistant pathogen renowned for its capacity to form protective biofilms that confer resistance to therapeutic agents. The present study investigated a nanocomposite system comprising chitosan-coated iron oxide nanoparticles conjugated with oxacillin (IONPs-CS-OXA) with the aim of enhancing antimicrobial and antibiofilm efficacy against MRSA. Iron oxide nanoparticles were synthesized via chemical co-precipitation, subsequently coated with chitosan, and conjugated with oxacillin. The nanocomposite was characterized by UV-Vis spectroscopy, FT-IR, XRD, zeta potential analysis, DLS, FE-SEM, and TEM. Multidrug-resistant MRSA isolates obtained from clinical specimens were subjected to antibiotic susceptibility testing, biofilm quantification, minimum inhibitory concentration (MIC) determination, and assessment of antimicrobial and antibiofilm activity. Biocompatibility was evaluated via MTT assays using HdFn and WRL-68 cell lines. Physicochemical characterization confirmed the successful fabrication of spherical IONPs-CS-OXA nanoparticles with nanoscale dimensions and a stable surface charge. MRSA isolates demonstrated high resistance to multiple antibiotics, including oxacillin. The nanocomposite markedly enhanced antimicrobial efficacy, as evidenced by significantly lower MIC values relative to free oxacillin. Inhibition zones were notably enlarged against tested MRSA strains, while biofilm formation was reduced by 54-88%. Cytotoxicity assays confirmed minimal adverse effects on normal cells, with cell viability exceeding 80%. The synergistic interaction among chitosan, iron oxide nanoparticles, and oxacillin conferred enhanced antibacterial and antibiofilm performance alongside acceptable biocompatibility. The IONPs-CS-OXA nanocomposite constitutes a promising candidate platform that, subject to further validation, may augment antibiotic delivery and help combat multidrug-resistant MRSA infections.