A silver lining in MRSA treatment: The synergistic action of poloxamer-stabilized silver nanoparticles and methicillin against antimicrobial resistance

Background: Increasing antibiotic resistance in bacterial infections, including drug-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), necessitates innovative therapeutic solutions. Silver nano- particles are promising for combating infections, but toxicity concerns emphasize the importance of factors like dosage, size, shape, and surface chemistry. Hence, exploring poloxamer as a stabilizing agent to reduce its toxicity and enhance the antibacterial effect on MRSA is investigated. Methods: Silver nanoparticles stabilized with poloxamer (AgNPs@Pol) were synthesized through the chemical reduction method and characterized using UV-visible spectrophotometer, HR-TEM, DLS, and Zeta potential measurements. Subsequently, the antibacterial activity of AgNPs@Pol alone and in combination with methicillin against MRSA and methicillin-susceptible S. aureus (MSSA) was evaluated using the broth microdilution method. Results: AgNPs@Pol showed significant efficacy against MRSA and MSSA, achieving a 100 % reduction in colony- forming units (CFU) at 9.7 mu g/ml. The minimum inhibitory concentration (MIC) against MRSA and MSSA was 8.6 mu g/ml and 4.3 mu g/ml, respectively. A synergistic effect was observed when AgNPs@Pol was combined with methicillin. Treatment with AgNPs@Pol increased reactive oxygen species (ROS) production in both strains, contributing to its antibacterial activity. Real-time qPCR analysis indicated the downregulation of genes involved in antimicrobial resistance and cell adhesion in both strains. Further, the 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) assay demonstrated low cytotoxicity for AgNPs@Pol against MCF-7, MG-63, and NIH-3T3 cell lines. Conclusion: The developed AgNPs@Pol demonstrated extensive colloidal stability, potent antibacterial activity and synergistic effect with methicillin against MRSA and MSSA. Further studies in primary cells and in vivo models may validate its potential for clinical applications.