Nasrin Ghassemi-Barghi
Isfahan University of Medical Sciences, Iran
Title: Recombinant human erythropoietin loading chitosan–tripolyphosphate nanoparticles: Application in attenuating mitoxantrone-induced genotoxicity in HepG2 cells
Biography
Biography: Nasrin Ghassemi-Barghi
Abstract
Mitoxantrone is an anti-neoplastic anthracenedione derivative that inhibits DNA replication and induces single and double strand breaks by intercalating in DNA through hydrogen bonding. Mitoxantrone is used in the treatment of certain types of cancer such as acute myeloid leukemia and is one of the few drugs approved for the treatment of progressive multiple sclerosis (MS).As a Topoisomerase II (TOP2) inhibitors ,mitoxantrone cause DNA damage in normal cells through apoptosis, mitochondrial dysfunction, free radical generation and lipid peroxidation. Erythropoietin (EPO) is an essential glycoprotein that facilitates red blood cell maturation from erythroid progenitors and mediates erythropoiesis. The use of recombinant human EPO (rHu-EPO) dramatically changed management of anemic patients with chronic kidney disease and improved their quality of life. Besides, recent research’s showed that (EPO) was a major component of tissue-protective system. EPO prevents apoptosis, reactive oxygen species generation and lipid peroxidation process. But the long-term or frequent administration of rHu-EPO due to its short half-life and high doses associated with adverse side effects such arterial hypertension, cerebral convulsion/hypertensive encephalopathy; thrombo-embolism,iron deficiency and influenza-like syndrome. One of the major reasons for the growing interest in nano-drug delivery systems is the potential to generate targeted delivery, decreased in doses and triggered release of drugs to specific cells and tissues. Therefor in this study we report first, the production and characterization of nanoparticles using the ionotropic gelation method between the biopolymer chitosan (CS) and tripolyphosphate (TPP) ion with simultaneous encapsulation of the glycoprotein rHu-EPO and subsequently explore the effect of CS-TPP-EPO nanoparticles in mitoxantrone-induced genotoxicity. For this purpose cells were incubated with regular rHu-EPO and rHu-EPO loading (CS-TPP) nanoparticle and mitoxantrone in pre and co-treatment condition. Our results showed that both regular rHu-EPO and rHu-EPO loading chitosan tripolyphosphate nanoparticles reduced the effects of mitoxantrone significantly by reduction of the level of DNA damage measured with the comet assay.