Ofloxacin-delivery system of a polyanhydride and polylactide blend used in the treatment of bone infection.

We developed a local drug-release system consisting of two biodegradable polymers, poly(sebacic anhydride) (PSA) and poly-D,L-lactide (PLA), for the treatment of chronic osteomyelitis. PSA and PLA were dissolved and blended at different ratios in tetrahydrofuran. Ofloxacin was loaded with an 8:1 weight ratio of the blend to the drug. The ofloxacin-containing beads of the PSA/PLA blend were made by preheating and compressing them in a mold. The in vitro drug release showed that changing the ratio between the two polymers caused the effective ofloxacin-release duration to vary from 6 to 68 days. The ofloxacin-containing beads with 10% PSA and 90% PLA produced an inhibition zone for the bacteria Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa within 89 days of the experiment. The in vivo drug release of the beads in rabbits demonstrated that the average ofloxacin concentration in the local bone was 20.1 +/- 10.3 microg/g, while that in the plasma was 35.6 +/- 18.8 ng/mL, within 8 weeks. Roentgenography, bacterial cultures, and histological examinations showed that the local release of ofloxacin by the beads could cure osteomyelitis in rabbits. Our findings suggested that using PSA/PLA blends with different ratios as carriers for antibiotics might be useful in the treatment of chronic osteomyelitis and in the prophylaxis of bone infection.