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Creation ofPolumeric Drugs and Drug Carriers Possessing Pilot Molecules on the Surface and Their Application for Targeting Therapy

表面具有先导分子的高分子药物和药物载体的制备及其在靶向治疗中的应用

基本信息

批准号：
11480261
负责人：
YUKIO Nagasaki
金额：
$ 6.21万
依托单位：
SCIENCE UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

We have been focusing on synthesis of several types of heterotelechelic poly(ethylene glycol), which denotes PEG possessing a functional group at one end and another functional group at the other chain end, both selectively and quantitatively. Utilizing these heteroPEG, lactose-PEG-SOD conjugate were prepared. The conjugate was found to incorporate preferentially to hepatocells such as HepG2 and HL60, via receptor mediated endocytosis.Using heteroPEG as macroinitiator for an anionic ring opening polymerization of lactide, PEG/PLA amphiphilic block copolymers possessing a functional group at PEG chain end were synthesized. The block copolymer forms core-shell type polymeric micelle in aqueous media having several tens nanometer size. The core-shell type polymeric micelle can solubilize hydrophobic drugs, which increases drug circulation in blood stream and reduces a toxicity of the drug due to the separation of the drug from the blood and tissues by the hydrophilic shell of the micelle. Consequently, polymer micelle-drug complexes show remarkable improvement in drug efficiencies, which is anticipated as one of the new nano-technology sciences for next generation.The most important point of the polymeric micelles thus prepared was the surface of the micelle. Since the PEG chain end locates on the periphery of the micelle, the surface should be functionalized by the PEG end group. Several ligands were installed on the surface of the PEG/PLA micelle. Finally, we observed specific interaction of the ligands on the micelle surface and receptor not only protein but also specific cells.On the basis of the investigations, new active targeting techniques will be opened.

我们一直专注于合成几种类型的heterotelechelic聚（乙二醇），这是指PEG具有一个功能团在一端和另一个功能团在另一个链端，无论是选择性和定量。利用这些杂聚乙二醇制备乳糖-聚乙二醇-超氧化物歧化酶结合物。以聚乙二醇（PEG）为大分子引发剂，通过丙交酯的阴离子开环聚合，合成了PEG/PLA两亲性嵌段共聚物。该嵌段共聚物在水介质中形成核-壳型聚合物胶束，粒径为几十纳米。核-壳型聚合物胶束可以溶解疏水性药物，这增加了血流中的药物循环，并由于胶束的亲水性壳将药物与血液和组织分离而降低了药物的毒性。因此，聚合物胶束-药物复合物在药物效率方面有显著的提高，有望成为下一代纳米技术的新领域之一。由于PEG链端位于胶束的外围，因此表面应该由PEG端基官能化。在PEG/PLA胶束表面安装了几个配体。最后，我们观察到胶束表面的配体不仅与蛋白质而且与特定细胞的特异性相互作用，在此基础上，将开辟新的主动靶向技术。