Kyotani S, Nishioka Y, Okamura M, Tanaka T, Miyazaki M, Ohnishi S, Yamamoto Y, Ito K, Ogiso T, Tanada S
Department of Pharmacy, Kochi Medical School Hospital, Japan.
Chem Pharm Bull (Tokyo). 1992 Oct;40(10):2814-6. doi: 10.1248/cpb.40.2814.
As an effective therapy for hepatocellular carcinoma, hepatic arterial chemo-embolization therapy has been widely used, and many embolizing materials have been extensively investigated. In the present study, we prepared various types of cis-diamminedichloroplatinum(II) (CDDP) albumin microspheres using chitin and chitosan, both of which have attracted considerable attention as new non-toxic biological polymer materials having favorable characteristics such as immune adjuvant activity, biological compatibility, and biodegradation. Hepatic artery of rabbit hepatic cancer models, which had transplanted VX2 tumors, were embolized with various types of microspheres. The anti-tumor effects and tumor-targeting of the microspheres, and the effects of the microspheres administration on the hepatic tissue were investigated. As a result, anti-tumor activity of the microspheres was increased by the addition of chitin-containing or chitosan treated materials; tumor growth rates of chitin addition and chitosan treated groups were approximately 160% and 120%, respectively, and were significantly lower than that of the non-treatment groups with a rate of approximately 580%. However, complete inhibition of tumor growth might have been impossible. Anti-tumor activity was increased by the addition of chitin-containing or chitosan treated materials. Whereas the growth inhibitory effect was insufficient, in order to potentiate anti-tumor activity, higher CDDP contents and sustained release of CDDP at a high level from microsphere and so on should be essentially improved for the near future. The CDDP level in hepatic tissue following the administration of microspheres was increased by adding chitin to the microspheres or by treating the microspheres with chitosan.(ABSTRACT TRUNCATED AT 250 WORDS)
作为肝细胞癌的一种有效治疗方法，肝动脉化疗栓塞疗法已被广泛应用，并且许多栓塞材料已得到广泛研究。在本研究中，我们使用几丁质和壳聚糖制备了各种类型的顺二氯二氨铂（II）（CDDP）白蛋白微球，这两种物质作为具有免疫佐剂活性、生物相容性和生物降解性等良好特性的新型无毒生物聚合物材料已引起了相当大的关注。用各种类型的微球栓塞移植了VX2肿瘤的兔肝癌模型的肝动脉。研究了微球的抗肿瘤作用和肿瘤靶向性，以及微球给药对肝组织的影响。结果，添加含几丁质或经壳聚糖处理的材料可提高微球的抗肿瘤活性；添加几丁质组和经壳聚糖处理组的肿瘤生长率分别约为160%和120%，明显低于未治疗组的约580%。然而，完全抑制肿瘤生长可能是不可能的。添加含几丁质或经壳聚糖处理的材料可提高抗肿瘤活性。尽管生长抑制作用不足，但为了增强抗肿瘤活性，在不久的将来应从本质上改善更高的CDDP含量以及微球中CDDP的高水平持续释放等。通过向微球中添加几丁质或用壳聚糖处理微球，给药后肝组织中的CDDP水平会升高。（摘要截选至250字）
