A Study of Embolizing Materials for Chemo-embolization Therapy of Hepatocellular Carcinoma : Antitumor Effect of cis-Diamminedichloroplatinum(II) Albumin Microspheres, Containing Chitin and Treated with Chitosan on Rabbits with VX2 Hepatic Tumors

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-tomor 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. However, no difference was observed in the platinic concentration between the tumor portion and normal portion; thus, microspheres showed no tumor-targeting. Also, no effects of microsphere administration on functions of the liver or kidneys were observed. Based on these observations, we concluded that chitin or chitosan had an antitumor effect in VX2 rabbit hepatic tumor models and thereby were effective as embolizing materials.