Micellar carriers based on block copolymers of poly(e-caprolactone) and poly(ethylene glycol) for doxorubicin delivery
Micellar carriers based on block copolymers of poly(e-caprolactone) and poly(ethylene glycol) for doxorubicin delivery
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DOI：
10.1016/j.jconrel.2004.06.003
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发表时间：
2004-08-27
影响因子：
10.8
通讯作者：
Gao, JM
中科院分区：
文献类型：
--
作者：
Shuai, XT;Ai, H;Gao, JM
合成了不同组成的聚己内酯（PCL）和单甲氧基聚乙二醇（MPEG）的嵌段共聚物。两亲性嵌段共聚物在水溶液中自组装成纳米胶束，其疏水核包裹阿霉素（DOX）。胶束直径随着共聚物组合物中PCL嵌段长度（2.5-24.7 kDa）的增加而从22.9 nm增加到104.9 nm。溶血性研究表明，游离DOX在200 μ g/ml时引起11%的溶血，而在相同药物浓度下用DOX负载的胶束没有检测到溶血。在37 ℃下的体外研究表明，在pH 5.0下从胶束中释放DOX比在pH 7.4下快得多。共聚焦激光扫描显微镜（CLSM）表明，DOX负载胶束积累主要是在细胞质中，而不是细胞核，在自由DOX相反。与体外释放和CLSM结果一致，细胞毒性研究表明，DOX负载的胶束在人MCF-7乳腺癌细胞中表现出延迟的细胞毒性。(C)2004 Elsevier B. V.保留所有权利。
Diblock copolymers of poly(epsilon-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hernolytic studies showed that free DOX caused 11% hemolysis at 200 mug ml(-1), while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 degreesC demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. (C) 2004 Elsevier B.V. All rights reserved.