EFFICACY OF SLOW-RELEASING ANTICANCER DRUG-DELIVERY SYSTEMS ON TRANSPLANTABLE OSTEOSARCOMAS IN RATS

New drug delivery systems for cis-diamminedichloroplatinum (CDDP) inco rporated into vehicles, such as polymethylmethacrylate (PMMA), fibrin glue (F.G.), alpha-tricalciumphosphate (TCP) and ethylenevinyleacelate copolymer (Polymer) were examined using a rat osteosarcoma model. The materials containing CDDP were directly implanted into the tumors or subcutaneous tissue of rats, and the inhibitory effects on tumor growt h and lung metastasis were evaluated. Data on in vitro kinetics of CDD P release revealed good results for both TCP and F.C., and the release pattern from TCP to be most appropriate for a slow-releasing drug del ivery system. This was supported by the results of the implantation ex periments, whereby the direct implantation of TCP containing CDDP (CDD P-TCP) into tumors, gave significantly better inhibitions of tumor gro wth and metastasis than either non-treatment (P<0.01) or subcutaneous implantation (P<0.05). In a second experiment, using different adminis tration procedures, different inhibitory effects on tumor growth and l ung metastatic potency were observed with intra-arterial and intraveno us CDDP administration, as well as with CDDP-TCP implanted subcutaneou sly. Suppression effects of CDDP (10 mg/kg)-TCP directly implanted int o tumors were equal to those of intra-arterial (2.5 mg/kg) and intrave nous (5.0 mg/kg) administrations. The present results suggest CDDP-TCP implantation to be effective as a slow-release drug delivery system f or inhibiting tumor growth and metastasis, and that it should be a use ful adjuvant to conventional. i.v. or i.a. chemotherapy.