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

Authors :
Chiou, Brian
Neal, Emma H.
Bowman, Aaron B.
Lippmann, Ethan S.
Simpson, Ian A.
Connor, James R.
Source :
PLoS ONE; 6/11/2018, Vol. 13 Issue 6, p1-12, 12p
Publication Year :
2018

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19326203
Volume :
13
Issue :
6
Database :
Complementary Index
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
130089287
Full Text :
https://doi.org/10.1371/journal.pone.0198775