Release of antibiotic from composites of hydroxyapatite and poly(lactic acid)

Abstract

We have recently revealed that a composite material prepared from hydroxyapatite and poly(lactic acid) can be used effectively as a substitute or a filler in the repair of bone defects. We have added the antibiotic Dideoxykanamycin B (DKB) to the composite to give it an antimicrobial property. To facilitate this purpose, d,l-lactic acid oligomers were synthesized. The release of the drug has been studied experimentally both in vitro and in vivo. For the study of in vivo release we prepared cylindrical composites of 40% oligomer, 40% hydroxyapatite and 20% DKB, by weight. The composites were implanted into the fenestrated tibias of rats; after predetermined periods of time the animals were sacrificed. Post implantation it has been found that the release rate of DKB gradually decreases with time; however, DKB remains at the implant site in sufficient amounts to prevent bacterial growth for a few weeks. DKB was also found to be concentrated in the kidney; however, the amount was low. The composites from the lower molecular weight oligomer showed a higher release rate.