151. Polymeric Nanoparticles Enhance the Ability of Deferoxamine To Deplete Hepatic and Systemic Iron
- Author
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Gregory J. Anderson, Linhao You, Yongwei Wang, Guangjun Nie, Tianqing Liu, Shanshan Guo, Gang Liu, David M. Frazer, and Jiaqi Xu
- Subjects
0301 basic medicine ,Iron Chelator ,Chemistry ,Mechanical Engineering ,Tissue iron ,Half-life ,Bioengineering ,General Chemistry ,Pharmacology ,Condensed Matter Physics ,Polymeric nanoparticles ,Deferoxamine ,Excretion ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine ,Iron dextran ,General Materials Science ,Hepatic iron ,030215 immunology ,medicine.drug - Abstract
Chelators are commonly used to remove excess iron in iron-loading disorders. Deferoxamine (DFO) is an effective and safe iron chelator but an onerous parenteral administration regimen limits its routine use. To develop more effective methods for delivering iron chelators, we examined whether amphiphilic copolymer nanoparticles (NPs) could deliver DFO more efficiently. Physical characterization showed a uniform and stable preparation of DFO nanoparticles (DFO-NPs) with an average diameter of 105.3 nm. In macrophage (RAW264.7) and hepatoma (HepG2) cell lines, DFO-NPs proved more effective at depleting iron than free DFO. In wild-type mice previously loaded with iron dextran, as well as Hbbth3/+ and Hfe–/– mice, which are predisposed to iron loading, DFO-NPs (40 mg/kg DFO; alternate days; 4 weeks) reduced hepatic iron levels by 71, 46, and 37%, respectively, whereas the equivalent values for free DFO were 53, 7, and 15%. Staining for tissue iron and urinary iron excretion confirmed these findings. Pharmacoki...
- Published
- 2018