Cytotoxic Effects of Targeted Galactosylated Pluronic F127/PluronicL122 Nano-Sized Micelles Loaded with Doxorubicin in Human Hepatocellular Carcinoma Cell Line

Abstract

Background: Asialoglycoprotein receptors are among the most important over-expressed receptors in hepatocellular carcinoma (HepG2). Decorating drug carrier to specific ligands of these receptors can enhance their absorption to cells and elevate their permeability to hepatoma cells. This can reduce the side effects of the drug in nonspecific tissues and enhance drug efficiency. The aim of the present work was to evaluate the cytotoxicity of doxorubicin-loaded mixed micelles of galactosylated Pluronic F127/L122 on HepG2 cells. Methods: Galactosylated Pluronic F127 was synthesized. Doxorubicin-loaded nano-sized micelles were prepared by direct dissolution method. Based on particle size, zeta potential, polydispersity index, loading efficiency and release efficiency of doxorubicin from nano-sized micelles, optimized micelles were used for cytotoxicity test on HepG2 cells by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Findings: The optimum targeted nano-sized micelles had particle size of 197.9 ± 2.1 nm, zeta potential of 18.6 mv, polydispersity index of 0.308 ± 0.058, loading efficiency of 78.3 ± 0.3%, and drug release efficiency of 32.5 ± 0.5% (until the third hour). Nano-sized micelles loaded with doxorubicin in concentrations of 0.2, 0.8, 3, 6 μM caused significantly higher cytotoxicity compared to non-targeted nano-sized micelles and free doxorubicin. Conclusion: Mixed targeted nano-sized micelles of galactosylated Pluronic F127 and Pluronic L122 loaded with doxorubicin showed more efficiency and specificity to toxicity against HepG2 cells than non-targeted nanoparticles and free drug. Keywords: Targeted mixed nano-sized micelles, Doxorubicin, Hepatocellular carcinoma, HepG2, 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay