Self-assembled polymeric micellar nanoparticles as nanocarriers for poorly soluble anticancer drug ethaselen.
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.
Li
Xinru
X
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, 100191, Beijing, Haidian, People's Republic of China. yanliu@bjmu.edu.cn.
Yang
Zhuoli
Z
Yang
Kewei
K
Zhou
Yanxia
Y
Chen
Xingwei
X
Zhang
Yanhui
Y
Wang
Fei
F
Liu
Yan
Y
Ren
Lijun
L