Self-Assembled Polymeric Micellar Nanoparticles as Nanocarriers for Poorly Soluble Anticancer Drug Ethaselen

Xinru Li,Lijun Ren,Yanhui Zhang,Fei Wang,Yanxia Zhou,Kewei Yang,Zhuoli Yang,Xingwei Chen,Yan Liu

doi:10.1007/s11671-009-9427-2

Abstract

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.

Highlights

BBSKE (Fig. 1), chemically named (1,2-[bis(1,2-benzisoselenazol-3(2H)-one)]ethane), is a novel organic selenium compound, which is one of the derivatives of ethaselen (For convenience, ethaselen is referred to BBSKE in this study)
Results and Discussion mPEG-PLA copolymers were synthesized by ring-opening polymerization of D,L-dilactide by using mPEG as initiator
The diameter derived from transmission electron microscopy (TEM) was lower than that from dynamic light scattering (DLS), which could be assigned to the dehydration and shrinkage of the micelles during drying. These results indicated that the ethaselen-loaded polymeric micelles were well dispersed in aqueous media and formed homogeneous nanosized micelle structures

Summary

Introduction

BBSKE (Fig. 1), chemically named (1,2-[bis(1,2-benzisoselenazol-3(2H)-one)]ethane), is a novel organic selenium compound, which is one of the derivatives of ethaselen (For convenience, ethaselen is referred to BBSKE in this study). It showed a positive antitumor activity and became a potential anticancer agent with lower toxicity and side effects [1, 2]. Ethaselen is poorly soluble in water (2.57 lg/mL) and in commonly used organic solvents such as methanol, ethanol, ether and chloroform. Its bioavailability by oral administration is considerably low. Poor solubility creates major obstacles for formulations and successful chemotherapy with ethaselen. Several methods including drug delivery systems were investigated [3], developing a ethaselen delivery system for higher selectivity, efficient solubilization and delivery of ethaselen to the intended site without provoking any adverse reactions is still a challenge

Methods

Results

Conclusion