Poly(ethylene glycol) multiblock copolymer as a carrier of anti-cancer drug doxorubicin
Poly(ethylene glycol) multiblock copolymer as a carrier of anti-cancer drug doxorubicin
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DOI：
10.1021/bc990092l
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发表时间：
2000-03-01
影响因子：
4.7
通讯作者：
Schacht, EH
中科院分区：
文献类型：
--
作者：
Pechar, M;Ulbrich, K;Schacht, EH
合成了一种基于可生物降解的聚乙二醇型嵌段共聚物的新型水溶性聚合物药物载体体系。通过二胺与聚乙二醇双(琥珀酰亚胺碳酸酯)的界面缩聚反应，制备了由分子量为2000的聚乙二醇链段组成的带有氨基端基的聚乙二醇单嵌段共聚物。由谷氨酸和赖氨酸残基组成的寡肽二胺的结构被设计为组织蛋白酶B的底物，组织蛋白酶B是一种溶酶体酶，被认为是体内降解聚合物载体的酶之一。载体中包含的每个寡肽块包含三个羧基，其中一些用于通过四肽间隔物Gly-Phe-Leu-Gly连接抗癌药物阿霉素(Dox)。这种四肽间隔区对酶解很敏感。此外，还展示了Dox的体外释放和组织蛋白酶B对聚合链的降解，以及对该结合物的体内抗癌活性的初步评价。
The synthesis of a novel water-soluble polymer drug carrier system based on biodegradable poly(ethylene glycol) block copolymer is described in this paper. The copolymer consisting of PEG blocks of molecular weight 2000 Linked by means of an oligopeptide with amino end groups was prepared by interfacial polycondensation of the diamine and PEG bis(succinimidyl carbonate). The structure of the oligopeptide diamine consisting of glutamic acid and lysine residues was designed as a substrate for cathepsin B, a lysosomal enzyme, which was assumed to be one of the enzymes responsible for the degradation of the polymer carrier in vivo. Each of the oligopeptide blocks incorporated in the carrier contained three carboxylic groups of which some were used for attachment of an anti-cancer drug, doxorubicin (Dox), via a tetrapeptide spacer Gly-Phe-Leu-Gly. This tetrapeptide spacer is susceptible to enzymatic hydrolysis. In vitro release of Dox and the degradation of the polymer chain by cathepsin B as well as preliminary evaluation of in vivo anti-cancer activity of the conjugate are also demonstrated.