Plaster of Paris implants containing vancomycin (60 mg/g of carrier) were prepared in order to be used as local delivery system for the treatment of bone infections. The regulation of the release rate was performed by coating the carrier with a polylactide-co-glycolide polymer composed by 10% (w/w) polyglycolic acid and 90% (w/w) racemic poly (D,L-lactic acid). The release of the antibiotic from the biodegradable matrix was evaluated in vitro. From this investigation, it is clear that the drug elution depends on the coating depth. After a burst effect occurring on the first day of the experiment, therapeutic concentrations were measured during one week when uncoated implants were used. The coating allowed decrease of the burst effect and extended efficient release to more than five weeks when the implants were embedded with six layers (162 microns) of PLA45GA10. This delivery system was implanted into the femoral condyle of rabbits. It was shown that the in vivo release was also closely regulated by the coating depth. In all bone tissues (bone marrow and cortical bone) surrounding the pellets, the drug concentration exceeded the Minimum Inhibitory Concentration for the common causative organisms of bone infections (Staphylococcus aureus) for at least four weeks without inducing serum toxic levels. Due to its cheapness, facility of use and sterilization, biocompatibility and biodegradability, plaster of Paris coated with PLA45GA10 polymer giving a controlled release of vancomycin appears to be a promising sustained release delivery system of antibiotics for the treatment of bone and joint infections.

Local antibiotic therapy by diffusion from plaster of Paris beads has proved promising in bone surgery. Sustained local delivery depends on thermostability, so we tested the antibacterial activity of 11 antibiotic solutions after storage at 37 degrees C using a microbiological method. Cephalosporins and penicillins were unstable, but aminoglycosides remained fully stable with 100% activity after 2 weeks. About 60% of the initial bactericidal activity of quinolone, glycopeptides and sodium fusidate were still detectable after 2 weeks. Release of these antibiotics from plaster of Paris beads was evaluated in vitro. Even those in the same family differed in their release rate. Plaster beads with sodium fusidate were the most effective association. A therapeutic level of glycopeptides, aminoglycosides and amoxicillin was leached for about 3 weeks. Cephalosporins and sodium amoxicillin were released in 2 to 3 days, and quinolone beads were too brittle to be used. Plaster of Paris, which is cheap, biocompatible and biodegradable, is an excellent carrier for sodium fusidate, aminoglycosides and glycopeptides.

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