Controlled Release of an Antibiotic Drug from Poly-L-Lactic Acid Coated Implants for Bacterial Infection Treatment

Implantation failure due to bacterial infection incurs significant medical expenditure annually, and treatment tends to be complicated. This study proposes a preventive treatment of bacterial infection in implants using an antibiotic delivery system consisting of vancomycin loaded into poly-l-lactic acid matrices. A thin layer of this antibiotic-containing polymer was formed on stainless steel surfaces using a simple dip-coating method. SEM images of the polymeric layer revealed a honeycomb structure of the PLLA network with the entrapment of vancomycin molecules inside. In the in vitrorelease study, a rapid burst release was observed, followed by a sustained release of vancomycin for approximately 3 days. To extend the release time, a drug-free topcoat of PLLA was introduced to provide a diffusion resistance layer. As expected, the formulation with the drug-free topcoat exhibited a significant extension of the release time to approximately three weeks. The amount of vancomycin released from both formulations was best fitted with the Korsmeyer-Peppas model, indicating that the mechanism of vancomycin release from PLLA coating was dominantly controlled by Fickian diffusion. The agar diffusion assay and survival assay were performed to confirm the antibacterial activity of this vancomycin delivery system. Our results showed that the proposed antibiotic delivery system using PLLA coating could be used to successfully treat bacterial infection that may occur after orthopedic implantation. For simulation, the agar diffusion assay was selected for validation which the simulation results provided the comparable data to the experimental results, ensuring that the models used in this study was appropriate. The simulation of a bone plate revealed that there was a sufficient amount of vancomycin to inhibit the growth of bacteria in the surrounding tissues and in the cortical bone, but the concentration of vancomycin in both areas exceeded the renal toxicity level. Although the concentration of vancomycin in the cortical bone was higher than toxicity level, AUC_24h explained that there was no nephrotoxicity in the bone region. However, it could not be concluded that it was renal toxic in the surrounding tissues because the threshold concentration was determined in blood plasma, not in the tissues. Additional information and analysis are necessary to confirm the toxicity of the system. In conclusion, vancomycin-loaded PLLA coated stainless steel with drug-free topcoat was the most suitable formulation in all aspects, including release profile, therapeutic efficacy, and future application.