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肝细胞癌化疗栓塞治疗中栓塞材料的研究:几丁质浓度对顺二氯二氨铂(II)白蛋白微球性质及VX2肝细胞癌模型兔抗肿瘤效果的影响

A study of embolizing materials for chemo-embolization therapy of hepatocellular carcinoma: effects of chitin concentration on cis-diamminedichloroplatinum(II) albumin microsphere properties and antitumor effect in VX2 hepatocellular carcinoma model rabbits.

作者信息

Nishioka Y, Kyotani S, Okamura M, Ohnishi S, Yamamoto Y, Tanada S, Nakamura T

机构信息

Department of Pharmacy, Kochi Medical School Hospital, Japan.

出版信息

Biol Pharm Bull. 1993 Nov;16(11):1136-9. doi: 10.1248/bpb.16.1136.

DOI:10.1248/bpb.16.1136
PMID:8312871
Abstract

cis-Diamminedichloroplatinum(II) (CDDP) albumin microspheres were prepared with various chitin concentrations and microsphere CDDP contents, specific surface area, surface structure and other microsphere properties. CDDP release in vitro and the antitumor effect in VX2 tumor model rabbits were investigated. CDDP content was increased as the concentration of chitin increased; at a chitin concentration of 6.0% it was about 2 times that without chitin. Specific surface area also increased with chitin concentration. CDDP release rate from various microspheres in vitro was suppressed as chitin concentration increased. Thus, microsphere properties, especially surface structure, are affected by an increase in chitin concentration. In experiments in vivo, various microspheres were injected into the hepatic artery of VX2 hepatocellular carcinoma model rabbits, and the effects of the chitin concentration on the time course of blood platinum (Pt) level and the antitumor effect were assessed. The blood Pt concentration increased with increase in chitin concentration, with a maximum of 0.45 microgram/ml at a concentration of 6.0%, even 7 d following microsphere administration. Tumor growth was suppressed when the chitin concentration was increased. Tissue Pt concentrations also increased in the presence of chitin. These findings suggest that increasing the chitin concentration might promote microsphere decomposition and hence CDDP release in vivo, thus improving immunopotentiating activity and resulting in enhanced CDDP antitumor effect. The detailed mechanisms of the action, however remains to be studied.

摘要

采用不同的甲壳素浓度、微球顺铂(CDDP)含量、比表面积、表面结构及其他微球性质制备了顺二氨二氯铂(II)(CDDP)白蛋白微球。研究了CDDP的体外释放及对VX2肿瘤模型兔的抗肿瘤作用。随着甲壳素浓度的增加,CDDP含量升高;甲壳素浓度为6.0%时,其含量约为无甲壳素时的2倍。比表面积也随甲壳素浓度的增加而增大。随着甲壳素浓度的增加,各种微球在体外的CDDP释放速率受到抑制。因此,微球性质,尤其是表面结构,受甲壳素浓度增加的影响。在体内实验中,将各种微球注入VX2肝细胞癌模型兔的肝动脉,评估甲壳素浓度对血铂(Pt)水平时间进程和抗肿瘤作用的影响。血Pt浓度随甲壳素浓度的增加而升高,在浓度为6.0%时,即使在微球给药7 d后,血Pt浓度最高可达0.45μg/ml。当甲壳素浓度增加时,肿瘤生长受到抑制。在有甲壳素存在的情况下,组织Pt浓度也升高。这些发现表明,增加甲壳素浓度可能促进微球分解,从而促进CDDP在体内的释放,从而提高免疫增强活性,增强CDDP的抗肿瘤作用。然而,其详细作用机制仍有待研究。

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