Optimized formulation of vancomycin loaded thermoreversible hydrogel for treatment of orthopedic infections

Abstract

The aim of the present study was to develop suitable controlled release injectable vancomycin thermoreversible chitosan/ β-glycerophosphate hydrogel system for treatment of orthopedic infections. The effect of different formulation variables on the gelation temperature was studied. The prepared vancomycin loaded Chitosan/β-glycerophosphate thermoreversible hydrogels were characterized regarding gelation temperature, in-vitro vancomycin release and enzymatic degradation rate in presence of lysozyme. Antimicrobial activity of the released vancomycin was tested against the gram-positive methicillin resistant Staphylococcus aureus (MRSA) by agar diffusion method. The results showed that chitosan/ β-glycerophosphate solution were able to form gels at body temperature depending on chitosan degree of deacetylation, concentration, pH and β-GP concentration. The prepared thermoreversible hydrogels sustained vancomycin release for 21 days. Released vancomycin concentrations ranged from 3 to 95 folds the reported minimal inhibition concentration (MIC 90) for MRSA at all release study time points. Chitosan/β-glycerophosphate thermoreversible hydrogels were enzymatically degradable and 17.57% of the gel weight remained after 21 days. The preserved antimicrobial activity found after release of the antibiotic from the hydrogel elected this delivery system for further in-vivo and toxicological investigations.