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Background Septic arthritis is a worse condition of RA that is associated with significant morbidity and mortality. Septic arthritis develops due to direct introduction or invasion of pathogens. The objective of the present study was to formulate Vancomycin hydrochloride-loaded microspheres (VMS) based on Box–Behnken design (BBD) and evaluate its efficacy against septic arthritis. The intraarticular administration of optimized Vancomycin hydrochloride-loaded microspheres (OVMS) can reduce dose size, dosing frequency and systemic exposure with local targeted delivery. Results OVMS was further characterized for its drug–polymer compatibility using differential scanning calorimetry and Fourier transmission infrared spectroscopy. In vitro antibacterial activity was determined using the cup–plate method and in vivo anti-arthritic efficacy was evaluated by gross examination of septic arthritis. DSC and FTIR studies exhibited no interaction or incompatibilities between the drug and polymer. SEM images revealed that OVMS were spherical. It followed the first-order release rate according to Fick's law. The micromeritic properties indicated good flow property of OVMS. The zone of inhibition by OVMS was 1.5 cm against  S. aureus . In vivo antibacterial study revealed that OVMS was significant in reducing septic arthritis and bacterial load, i.e., 110.1 CFU/ml in comparison with the control group (850 CFU/ml). Conclusions Thus, OVMS may be used as an effective formulation for the treatment of septic arthritis as compared to marketed IV vancomycin injection after clinical studies.

DoE approach for development of localized controlled release microspheres of Vancomycin for treatment of septic arthritis