Park Eun Kyoung, Kim So Yeon, Lee Sang Bong, Lee Young Moo
School of Chemical Engineering, College of Engineering, Hanyang University, Seoul, South Korea.
J Control Release. 2005 Dec 5;109(1-3):158-68. doi: 10.1016/j.jconrel.2005.09.039. Epub 2005 Nov 2.
Amphiphilic block copolymers composed of methoxy poly(ethylene glycol) (MPEG) and poly(epsilon-caprolactone) (PCL) were synthesized and then conjugated with folic acid to produce a folate-receptor-targeted drug carrier for tumor-specific drug delivery. Folate-conjugated MPEG/PCL micelles containing the anticancer drug paclitaxel were prepared by micelle formation in aqueous medium. The size of the folate-conjugated MPEG/PCL micelles formed was about 50-130 nm, depending on the molecular weight of block copolymers, and was maintained at less than 150 nm even after loading with paclitaxel. The in vitro release profile of the paclitaxel from the MPEG/PCL micelles exhibited no initial burst release and showed sustained release. Paclitaxel-loaded folate-conjugated MPEG/PCL micelles (PFOL50) exhibited much higher cytotoxicity for cancer cells, such as MCF-7 and HeLa cells, than MPEG/PCL micelles without the folate group (PMEP50). Confocal image analysis revealed that fluorescent paclitaxel-loaded PFOL50 micelles were endocytosed into MCF-7 cells through the interaction with overexpressed folate receptors on the surface of the cancer cells.
合成了由甲氧基聚（乙二醇）（MPEG）和聚（ε-己内酯）（PCL）组成的两亲性嵌段共聚物，然后将其与叶酸共轭，以制备用于肿瘤特异性药物递送的叶酸受体靶向药物载体。通过在水性介质中形成胶束来制备含有抗癌药物紫杉醇的叶酸共轭MPEG/PCL胶束。形成的叶酸共轭MPEG/PCL胶束的大小约为50-130nm，这取决于嵌段共聚物的分子量，并且即使在负载紫杉醇后也保持在150nm以下。紫杉醇从MPEG/PCL胶束中的体外释放曲线没有显示出初始突释，而是呈现出持续释放。负载紫杉醇的叶酸共轭MPEG/PCL胶束（PFOL50）对癌细胞，如MCF-7和HeLa细胞，显示出比没有叶酸基团的MPEG/PCL胶束（PMEP50）更高的细胞毒性。共聚焦图像分析表明，负载荧光紫杉醇的PFOL50胶束通过与癌细胞表面过度表达的叶酸受体相互作用而被内吞到MCF-7细胞中。
