Pharmaceutical iron formulations do not cross a model of the human blood-brain barrier

Brian Chiou, Emma H. Neal, Aaron B. Bowman, Ethan S. Lippmann, Ian Simpson, James Connor

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Whether iron formulations used therapeutically for a variety of conditions involving iron deficiency can deliver iron to the brain is a significant clinical question given the impact that iron loading has on the brain in neurodegenerative diseases. In this study, we examine the ability of 5 pharmaceutical iron formulations that are given intravenously for treatment of iron deficiency to cross an in vitro model of the blood-brain barrier. The model uses human brain endothelial cells derived from induced pluripotent stem cells. We report that, compared to the natural iron delivery proteins, transferrin and H-ferritin, the pharmaceutical iron formulations neither cross the blood-brain barrier model nor significantly load the endothelial cells with iron. Furthermore, we report that mimicking brain iron sufficiency or deficiency by exposing the endothelial cells to apo- or holo-transferrin does not alter the amount of iron compound transported by or loaded into the cells. Coupled with previous studies, we propose that pharmaceutical iron formulations must first be processed in macrophages to make iron bioavailable. The results of this study have significant clinical and mechanistic implications for the use of therapeutic iron formulations.

Original languageEnglish (US)
Article numbere0198775
JournalPloS one
Volume13
Issue number6
DOIs
StatePublished - Jun 1 2018

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Drug Compounding
blood-brain barrier
Blood-Brain Barrier
Iron
iron
drugs
Pharmaceutical Preparations
Brain
Endothelial cells
transferrin
Transferrin
endothelial cells
brain
Endothelial Cells
Iron Compounds
Neurodegenerative diseases
Apoferritins
Induced Pluripotent Stem Cells
Macrophages
neurodegenerative diseases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chiou, Brian ; Neal, Emma H. ; Bowman, Aaron B. ; Lippmann, Ethan S. ; Simpson, Ian ; Connor, James. / Pharmaceutical iron formulations do not cross a model of the human blood-brain barrier. In: PloS one. 2018 ; Vol. 13, No. 6.
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Pharmaceutical iron formulations do not cross a model of the human blood-brain barrier. / Chiou, Brian; Neal, Emma H.; Bowman, Aaron B.; Lippmann, Ethan S.; Simpson, Ian; Connor, James.

In: PloS one, Vol. 13, No. 6, e0198775, 01.06.2018.

Research output: Contribution to journalArticle

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