Department of Physics, University of Zabol, Zabol, P. O. Box 98613-35856, Iran.
Basic Veterinary Science Department, Veterinary medicine Faculty, University of Zabol, Zabol, P. O. Box. 98613-35856, Iran.
Life Sci. 2021 Apr 1;270:119146. doi: 10.1016/j.lfs.2021.119146. Epub 2021 Feb 2.
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 FeCl-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.
地拉罗司（DFX）在普朗尼克的存在下被制成油包水乳剂，以提高其口服生物利用度。动态光散射（DLS）测量的 DFX 载药微乳系统的粒径约为 9nm。在人脐静脉内皮（HUVEC）细胞上评估了 DFX 和 DFX 载药微乳的抗增殖和抗脂质过氧化作用。我们的体外结果表明，与 DFX 载药微乳相比，HUVEC 细胞对游离 DFX 更敏感。虽然游离和包封的 DFX 均能减弱 FeCl 诱导的脂质过氧化，但在 6 和 12h 处理后，DFX 载药微乳似乎不如 DFX 改善。为了比较游离 DFX 和 DFX 载药微乳在铁中毒大鼠体内的疗效，分别给大鼠口服 25mg/kg DFX 或 25mg/kg DFX 载药微乳。游离 DFX 的体内灌胃处理显著增加了血清生化参数。与对照组大鼠相比，接受游离 DFX 的大鼠脂质过氧化也明显增加。DFX 载药微乳的治疗恢复了血清 AST、ALT 和肌酐水平的升高，并降低了肝脏 MDA 含量。肾和肝组织的组织病理学分析与生化结果一致。总之，DFX 载药微乳引起的毒性比游离 DFX 小，在对抗铁过载并发症方面似乎是一种更理想、更安全的药物载体。进行了理论模拟，以更好地了解 DFX 与表面活性剂 F127 之间的相互作用。
