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Abstract
Local implantation or injection of microspheres containing bisphosphonates for site-specific therapy may aid in treating several pathological conditions associated with bone destruction. Chitosan microspheres containing two antiresorption and anticalcification agents, pamidronate and suberoylbisphosphonate (SuBP), were prepared from a w/o emulsion. Various formulation variables were studied for their effect on die release rate profile of these bone-seeking agents. Polymer coating of micromatrices yielded microspheres with the most retarded release rate, and the drug delivery system was found biocompatible in endothelial cell culture. The microspheres were examined in vitro and in vivo for release kinetics and drug disposition. The release of bisphosphonate from the microspheres was faster in vitro than in vivo. Drug disposition following implantation of microspheres in the tibialis muscle resulted in a relatively increased disposition in the adjacent tibia while injection of drug solution in the tibialis muscle resulted in uniform disposition of the drug in the femorae and tibiae. Bisphosphonate released from chitosan microspheres effectively inhibited bioprosthetic tissue calcification in die rat subdermal model.