Enhanced antibacterial properties of amoxicillin-loaded silver nanoparticles against Methicillin-resistant <i>Staphylococcus aureus</i> : physicochemical characterization, anti-virulence activity, and biofilm inhibition

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) presents significant challenges in healthcare and community settings due to its diverse virulence factors and increasing resistance to conventional antibiotics. Given the scarcity of effective treatments, developing innovative antibacterial strategies is essential. This study explores the potential of silver nanoparticles conjugated with acacia extracts as nanocarriers for amoxicillin to enhance antibacterial efficacy and circumvent resistance mechanisms in MRSA. The synthesized amoxicillin-loaded silver-acacia nanoparticles were characterized for their physicochemical properties, revealing spherical morphology with a minimum particle size of approximately 230 nm, a polydispersity index of 0.3, and a high negative zeta potential of -32 mV as confirmed by transmission electron microscopy. <i>In vitro</i> assays demonstrated that these nanoparticles significantly inhibited bacterial growth, achieving a reduction at a minimum inhibitory concentration (MIC) of 2 mg/mL. At this concentration, biofilm formation by MRSA was inhibited by 80%, as verified by scanning electron microscopy, and hemolytic activity on blood agar was completely suppressed. While a dose-dependent cytotoxic effect on endothelial cells was observed, the MIC concentration remained cytocompatible (<i>p</i> < 0.05). These findings underscore the promise of amoxicillin-loaded silver-acacia nanoparticles as potent antibacterial agents with minimal cytotoxicity at effective doses. This study highlights the potential of nanotechnology-enabled drug delivery to repurpose amoxicillin and offers a novel platform for combating multidrug-resistant MRSA infections, which may inform future therapeutic developments.