Key Laboratory of Functional Polymer Materials, Ministry of Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, China.
J Mater Sci Mater Med. 2011 Apr;22(4):853-63. doi: 10.1007/s10856-011-4262-2. Epub 2011 Mar 4.
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(γ-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 · HCl. The DOX-loaded micelles exhibited almost twofold more potent cytotoxicity compared with DOX · 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.
最近，人们致力于研究功能化胶束作为靶向药物传递载体的应用。在本研究中，制备了甘草次酸（GA，肝靶向配体）修饰的聚乙二醇-b-聚（γ-苄基 L-谷氨酸）胶束，并将其作为潜在的肝靶向药物载体进行了评价。考察了胶束的聚集行为、稳定性、粒径和形态。将抗癌药物阿霉素（DOX）包封在胶束中。研究了载药胶束的体外释药行为、体内分布以及对肝癌 QGY-7703 细胞的细胞毒性。结果表明，载药胶束的体外释药行为具有明显的 pH 依赖性，符合菲克扩散动力学。与游离 DOX·HCl 相比，胶束对肝脏具有明显的靶向性，使 DOX 的浓度增加了 4.9 倍。与 DOX·HCl 相比，载药胶束的细胞毒性提高了近两倍，且细胞毒性具有时间和剂量依赖性。这些结果表明，GA 功能化胶束是一种有前途的肝靶向药物传递载体。
