Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, 100191, Beijing, Haidian, People's Republic of China.
Nanoscale Res Lett. 2009 Sep 16;4(12):1502-11. doi: 10.1007/s11671-009-9427-2.
A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 μg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-β-CD inclusion were observed at the same dose in H22human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug.
一系列单甲氧基聚乙二醇-聚乳酸（mPEG-PLA）两亲嵌段共聚物被合成，mPEG-PLA 胶束被制备并用作一种纳米载体，用于溶解和输送有前途的抗癌药物乙硒啉。乙硒啉通过透析法有效地包封到胶束中，在冻干前其在水中的溶解度显著提高至 82μg/mL。载乙硒啉胶束的平均粒径为 51 至 98nm，具有较窄的粒径分布，且取决于 PLA 嵌段的长度。体外溶血研究表明，mPEG-PLA 共聚物和载乙硒啉的聚合物胶束对红细胞没有溶血作用。在相同剂量下，载乙硒啉聚合物胶束与乙硒啉-HP-β-CD 包合物相比，在荷 H22 人肝癌细胞的小鼠模型中具有增强的抗肿瘤疗效和降低的毒性作用。这些结果表明，mPEG-PLA 聚合物胶束纳米粒作为纳米载体具有很大的潜力，可有效溶解疏水性乙硒啉，并进一步降低药物的副作用和毒性。
