Effect of etanidazole-loaded nanoparticles on radiosensitization of hypoxic tumor cells

Objective: To prepare active and controlled etanidazole-loaded nanoparticles and to determine the ability to radiosensitize hypoxie human breast carcinoma cells (MCF-7) and human carcinoma cervices cells (HeLa). Methods: The poly (D, L-lactide-co-glycolide)(PLGA) nanoparticles containing etanidazole were prepared by w/o/w emulsification-solvent evaporation method. The drug loading efficiency, the encapsulation efficiency (EE) and the release profile in vitro were measured by high-performance liquid chromatography. The morphology of the etanidazole-loaded nanoparticles was investigated by transmission electron microscope. The size distribution of nanoparticles was determined by laser diffraction analyzer. Cell viability was measured by the ability of single cell to form colonies in vitro. Results: The prepared nanoparticles were spherical in shape with sizes between 90 and 190 nm. The drug loading efficiency and EE was 1.66% and 18.02%, respectively. The drug release pattern was biphasic with a fast release rate followed by a slow one. Co- culture of hypoxic MCF-7 and HeLa cells with etanidazole-loaded nanoparticles and free etanidazole demonstrated that released etanidazole effectively sensitized hypoxic tumor cells to irradiation. Compared with free etanidazole, radiosensitization of etanidazole-loaded nanoparticles was more significant. Conclusions: It is demonstrated that etanidazole can be effectively released from a biodegradable PLGA nanoparticle delivery system while maintaining potent radiosensitizing ability for hypoxic tumor cells. (authors)