Biochemical effects of deferasirox and deferasirox-loaded nanomicellesin iron-intoxicated rats.


Rahdar A(1), Hajinezhad MR(2), Sargazi S(3), Bilal M(4), Barani M(5), Karimi P(6), Kyzas GZ(7).
Author information:
(1)Department of Physics, University of Zabol, Zabol, P. O. Box 98613-35856, Iran. Electronic address: [Email]
(2)Basic Veterinary Science Department, Veterinary medicine Faculty, University of Zabol, Zabol, P. O. Box. 98613-35856, Iran. Electronic address: [Email]
(3)Cellular and molecule Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.
(4)School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China.
(5)Department of Chemistry, Shahid Bahonar University of Kerman, Kerman, Iran.
(6)Department of Chemistry, University of Zabol, Zabol, P. O. Box 98613-35856, Iran. Electronic address: [Email]
(7)Department of Chemistry, International Hellenic University, Kavala, Greece. Electronic address: [Email]


Deferasirox (DFX) was formulated into oil-in-water microemulsions in the presence of pluronicto improve its oral bioavailability. The size of the DFX-loadedmicroemulsions system measured by dynamic light scattering (DLS) was about 9 nm. The anti-proliferative and anti-lipid peroxidation effects of DFX and DFX-loaded microemulsions were assessed on Human umbilical vein endothelial (HUVEC) cells. Our in vitro results showed that HUVEC cells are more susceptible to free DFX as compared to DFX-loaded microemulsions. Although both free and encapsulated DFX attenuated FeCl3-induced lipid peroxidation, after 6 and 12 h treatment, DFX-loaded microemulsions did not appear a better ameliorator than DFX. To compare the in vivo efficacy of free DFX and DFX-loaded microemulsions in iron- intoxicated rats, the animals were orally administered with 25 mg/kg DFX, or 25 mg/kg DFX microemulsions, respectively. In vivo gavage handling of free DFX significantly increased serum biochemical parameters. There was also a significant increase in lipid peroxidation in rats who received free DFX compared to those in the control rats. Treatment with DFX-loaded microemulsions restored the elevated levels of serum AST, ALT, and creatinine levels and also reduced liver MDA content. Histopathological analysis of renal and hepatic tissues was in line with the biochemical results. In conclusion, DFX-loaded microemulsions induce less toxicity than free DFX and appear a more desirable and safer drug carrier in combating the iron-overload complications. Theoretical simulations are performed to get better insight regarding interactions between DFX and surfactant F127.