Design and evaluation of gamma-sterilized vancomycin hydrochloride-loaded poly(ε-caprolactone) microspheres for the treatment of biofilm-based medical device-related osteomyelitis

摘要

Abstract Context: There is a great necessity to find and use accomplished terminal sterilization technique for industrial manufacturing, research and development studies. Gamma (gamma)-sterilization has been commonly employed for wide range of products as indicated by the pharmacopoeias. However, carefully examination should be performed prior to administration since gamma-radiation can cause changes in drug and polymer excipients. No information is available in literature about gamma-sterilization effects on vancomycin HCI-loaded poly (ε-caprolactone) (PCL) microspheres. Objective: Formulations were developed using a different preparation approach for the treatment of medical device-related osteomyelitis, and gamma-sterilization effects on the physicochemical characterization of the formulations were examined. Methods: Water-in-oil-in-water (w/o/w) emulsion technique using polyvinyl alcohol (PVA) in inner and outer phase was applied to prepare formulations. Physicochemical properties of the formulations were investigated before and after gamma-sterilization and the antibacterial activity against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) were measured. Results: The particle size of the nonsterilized formulations were between 58 and 134 urn. 60% or 20% of vancomycin HCI were released from 42.500 Mn or 70.000-90.000 Mn PCL microspheres, respectively, in 24 h. No difference was observed in the particle size, drug-loading efficiency, morphology, in vitro release and antimicrobial activity of the formulations after gamma-sterilization (p>0.05).