Miura S, Mii Y, Miyauchi Y, Ohgushi H, Morishita T, Hohnoki K, Aoki M, Tamai S, Konishi Y
Department of Orthopedic Surgery, Nara Medical University.
Jpn J Clin Oncol. 1995 Jun;25(3):61-71.
New drug delivery systems for cis-diamminedichloroplatinum (CDDP) incorporated into vehicles, such as polymethylmethacrylate (PMMA), fibrin glue (F.G.), alpha-tricalciumphosphate (TCP) and ethylenevinyleacetate 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 growth and lung metastasis were evaluated. Data on in vitro kinetics of CDDP release revealed good results for both TCP and F.G., and the release pattern from TCP to be most appropriate for a slow-releasing drug delivery system. This was supported by the results of the implantation experiments, whereby the direct implantation of TCP containing CDDP (CDDP-TCP) into tumors, gave significantly better inhibitions of tumor growth and metastasis than either non-treatment (P < 0.01) or subcutaneous implantation (P < 0.05). In a second experiment, using different administration procedures, different inhibitory effects on tumor growth and lung metastatic potency were observed with intra-arterial and intravenous CDDP administration, as well as with CDDP-TCP implanted subcutaneously. Suppression effects of CDDP (10 mg/kg)-TCP directly implanted into tumors were equal to those of intra-arterial (2.5 mg/kg) and intravenous (5.0 mg/kg) administrations. The present results suggest CDDP-TCP implantation to be effective as a slow-release drug delivery system for inhibiting tumor growth and metastasis, and that it should be a useful adjuvant to conventional i.v. or i.a. chemotherapy.
利用大鼠骨肉瘤模型，对负载于聚甲基丙烯酸甲酯（PMMA）、纤维蛋白胶（F.G.）、α - 磷酸三钙（TCP）和乙烯 - 醋酸乙烯酯共聚物（聚合物）等载体中的顺二氨二氯铂（CDDP）新型给药系统进行了研究。将含CDDP的材料直接植入大鼠肿瘤或皮下组织，评估其对肿瘤生长和肺转移的抑制作用。CDDP体外释放动力学数据显示，TCP和F.G.的效果均良好，且TCP的释放模式最适合缓释给药系统。植入实验结果支持了这一点，即向肿瘤中直接植入含CDDP的TCP（CDDP - TCP），对肿瘤生长和转移的抑制作用明显优于未治疗组（P < 0.01）或皮下植入组（P < 0.05）。在第二项实验中，采用不同给药程序，观察到动脉内和静脉内给予CDDP以及皮下植入CDDP - TCP对肿瘤生长和肺转移潜能有不同的抑制作用。直接植入肿瘤的CDDP（10 mg/kg）- TCP的抑制效果与动脉内（2.5 mg/kg）和静脉内（5.0 mg/kg）给药的效果相当。目前的结果表明，CDDP - TCP植入作为一种缓释给药系统，对抑制肿瘤生长和转移有效，并且应该是传统静脉或动脉化疗的有用辅助手段。
