BIOERODIBLE POLYANHYDRIDES FOR ANTIBIOTIC DRUG DELIVERY - INVIVO OSTEOMYELITIS TREATMENT IN A RAT MODEL SYSTEM

Acute and chronic osteomyelitis can be difficult to treat by conventio nal means. Current methods of treatment involve the use of systemic an tibiotics, the local implantation of non-degradable drug carriers, and surgical debridement. Each method has specific drawbacks. We report o n the use of a new controlled release system utilizing gentamicin and bioerodible, biocompatible polymers (polyanhydrides) designed for drug delivery applications for the treatment of clinical osteomyelitis. We compared this system's ability to reduce bacterial levels in infected bone with that of conventional non-degradable delivery systems based on polymethylmethacrylate (PMMA) and gentamicin. Polyanhydride copolym ers of bis-carboxyphenoxypropane and sebacic acid P loaded with gentam icin sulfate and PMMA/gentamicin matrices were implanted in the long b ones of Sprague-Dawley rats infected with a strain of Staphylococcus a ureus. After 3 weeks of implantation, the polymeric delivery devices w ere removed and quantitative cultures were used to determine bacterial levels in bone. The polyanhydride/gentamicin matrices demonstrated si gnificant degradation over the 3 week implantation period. Levels of b acteria, measured in colony forming units, were significantly lower in bone implanted with the polyanhydride/gentamicin release system than in long bones of control animals without an implant (p < 0.01), of ani mals with a polyanhydride polymer implant alone (p < 0.01), and of ani mals with a PMMA/gentamicin implant (p = 0.03). Bioerodible polyanhydr ides show promise as a new treatment modality for infections in bone.