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In this research, the effect of layer-by-layer (spray and dip) coating followed by annealing of vancomycin (VCM) and poly(ε-caprolactone) nanospheres (PCLnp) on Schanz pins for prolonged antibacterial activity was investigated. Nanospheres were prepared using the high-pressure homogenizer method and characterized by both functional groups and particle size. The in vitrorelease profile revealed that after 28 days, the cumulative release of VCM from the VCM-PCLnp coated pins was 753.68 ± 0.19 μg. The coated pins released VCM at a concentration greater than the minimum inhibitory concentration (MIC) and sustained this release for 28 days. Irritation, hemolysis, sensitization, and cytotoxicity assays confirmed that VCM-PCLnp coated pins were highly biocompatible. Additionally, antibacterial assays against methicillin-resistant Staphylococcus aureus(MRSA) revealed prolonged antibacterial resistance. Specifically, the assays demonstrated effective inhibition of Staphylococcus aureus (S. aureus),including the methicillin-resistant strain. This approach involves coating the implants with antibiotics and polymeric nanospheres using a layer-by-layer (dip and spray) method to prolong their antibacterial activity. The results of this study show great promise for successfully treating implant-associated infections. Consequently, we recommend this method for coating other medical devices.