Apatite cement containing cis-diamminedichloroplatinum implanted in rabbit femur for sustained release of the anticancer drug and bone formation

Abstract

To treat malignant bone tumors, anticancer drugs are administered systemically, simultaneously with surgical therapy. However, drugs administered systemically have considerable invasive action on bone and other organs, and are also associated with various side effects. A bone-cementing material that can maintain high concentrations of anticancer drug at local sites and which can improve local structural weakness after tumor resection would constitute an ideal therapeutic means of treating malignant bone tumors. We therefore applied the concept of a drug delivery system and developed an implant containing calcium phosphate cement and the anticancer drug, cis-diamminedichloroplatinum (CDDP). The results of a sustained release test showed that the in-vitro cumulative release ratio of an implant containing 20% CDDP was over 60%, and a release rate of 0.1mg/day was maintained. Experiments in vivo, using adult rabbits implanted with 10% CDDP, showed that the platinum (Pt) concentration in local bone marrow was an average 3200μg/ tissue·g 6 weeks after implantation. The concentration of Pt in the systemically administered group was 0.2μg/tissue·g at 6 weeks. The Pt concentrations in other organs of the implanted group were: 3μg/tissue·g or less in the kidney, and 2μg/tissue·g or less in liver. These values were lower than those in the systemically administered group (3.5 and 2.1μg/tissue·g, respectively). Local bone formation was observed by 12 weeks after implantation. Our implant maintained high Pt concentrations at local sites and the bone that formed reinforced the implant.