Polymeric Nanoparticles Enhance the Ability of Deferoxamine to Deplete Hepatic and Systemic Iron

Shanshan Guo, Gang Liu, David M. Frazer, Tianqing Liu, Linhao You, Jiaqi Xu, Yongwei Wang, Gregory J. Anderson, Guangjun Nie

Research output: Contribution to journalArticle

7 Scopus citations

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. Pharmacokinetic analysis showed that NP-encapsulated DFO had a much longer elimination half-life than free DFO (48.63 ± 28.80 vs 1.46 ± 0.59 h), and that DFO-NPs could be readily taken up by tissues and in particular by hepatic Kupffer cells. In vitro, DFO-NPs were less toxic to several cell lines than free DFO, and in vivo they did not elicit any specific inflammatory responses or histological changes. Our results suggest that using a nanoformulation of DFO is a valuable strategy for improving its efficiency as an iron chelator and that this could broaden its clinical use for the treatment of human iron overload disorders.

Original languageEnglish (US)
Pages (from-to)5782-5790
Number of pages9
JournalNano Letters
Volume18
Issue number9
DOIs
StatePublished - Sep 12 2018

Keywords

  • Nanoformulation
  • deferoxamine
  • half-life
  • iron chelation
  • iron overload
  • macrophages

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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