Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier
Glycyrrhetinic acid-functionalized degradable micelles as liver-targeted drug carrier
复制标题
甘草次酸功能化可降解胶束作为肝脏靶向药物载体
DOI：
10.1007/s10856-011-4262-2
复制
发表时间：
2011-04-01
影响因子：
3.7
通讯作者：
Yuan, Zhi
中科院分区：
文献类型：
--
作者：
Huang, Wei;Wang, Wei;Yuan, Zhi
近年来，人们致力于研究功能化胶束作为靶向药物递送载体的应用。本研究制备了甘草次酸（GA，一种肝脏靶向配体）修饰的聚乙二醇-b-聚（γ-苄基L-谷氨酸）胶束，并对其作为潜在的肝脏靶向药物载体进行了评估。研究了胶束的聚集行为、稳定性、尺寸和形态。抗癌药物阿霉素（DOX）被封装在胶束中。研究了载有DOX的胶束的药物释放曲线、体内分布以及对肝癌QGY-7703细胞的细胞毒性。结果表明，释放曲线与 pH 值相关，符合 Fickian 扩散动力学。胶束显着靶向肝脏，诱导的 DOX 浓度比游离 DOX 中心点 HCl 高 4.9 倍。与 DOX 中心点 HCl 相比，负载 DOX 的胶束表现出几乎两倍的细胞毒性，并且细胞毒性呈时间和剂量依赖性。这些结果表明，GA 功能化胶束代表了一种有前途的肝脏药物递送载体。
Recently, many efforts have been devoted to investigating the application of functionalized micelles as targeted drug delivery carriers. In this study, glycyrrhetinic acid (GA, a liver targeting ligand) modified poly(ethylene glycol)-b-poly(gamma-benzyl l-glutamate) micelles were prepared and evaluated as a potential liver-targeted drug carrier. The aggregation behavior, stability, size and morphology of the micelles were investigated. Anticancer drug doxorubicin (DOX) was encapsulated in the micelles. The drug release profile, in vivo distribution and the cytotoxicity against hepatic carcinoma QGY-7703 cells of DOX-loaded micelles were studied. The results indicated that the release profile was pH-dependent with Fickian diffusion kinetics. The micelles were remarkably targeted to the liver, inducing a 4.9-fold higher DOX concentration than that for free DOX center dot HCl. The DOX-loaded micelles exhibited almost twofold more potent cytotoxicity compared with DOX center dot HCl, and the cytotoxicity was time- and dosage-dependent. These results suggest that GA-functionalized micelles represent a promising carrier for drug delivery to the liver.