Cytotoxic Effects of Chitosan/Retinoic Acid/Albumin Targeted Nanoparticles Loaded with Doxorubicin on Human Hepatoma Cells

Abstract

Background: Anthracyclines are used to treat different types of cancer including hepatocellular carcinoma. However, they have various side effects such as cardiotoxicity. Designing a drug delivery system which targets retinoic acid receptors in hepatocellular carcinoma can reduce these side effects. Methods: Chitosan/retinoic acid/albumin nanoparticles were prepared using a coacervation method. Nanoparticles which were optimized according to their particle size, zeta potential, polydispersity index, loading efficiency and release of doxorubicin, were used for further tests of cytotoxicity on HepG2 cells [by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] and cellular uptake tests (by fluorescent microscopy). Findings: The optimum targeted nanoparticles (with particle size of 286 ± 50.0 nm, zeta potential of 30.5 ± 3.6 mv, polydispersity index of 0.50 ± 0.06, loading efficiency of 43.6 ± 13.5%, and drug release of 56.17 ± 6.00%) in a concentration of 0.5 mg/ml were two to three times more cytotoxic than non-targeted nanoparticles and free drug. Their cellular uptake was also more. Conclusion: Chitosan/retinoic acid/albumin targeted nanoparticles loaded with doxorubicin could affect HepG2 cells more effectively than non-targeted nanoparticles and free drug. Keywords: Chitosan/retinoic acid/albumin nanoparticles, Doxorubicin, HepG2, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay