Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women

Jeannine Baumgartner,Hans Christian Winkler,Florentine Hilty,Siriporn Tuntipopipat,Michael B Zimmermann,Phatchari Mankong,Lizelle Zandberg,Sueppong Gowachirapant,Jan Rijn Zeevaart,Cor Bester

doi:10.1038/s41598-022-06701-x

Abstract

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g−1 and 188 m2g−1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g−1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.

Highlights

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear
Amorphous ferric orthophosphate with a SSA of 25 m 2 g−1 served as reference compound for BET and X-ray diffraction (XRD) measurements. FePO4-NPs for the human study were produced from stable isotope (57Fe) enriched precursors, bulk FePO4 and FeSO4 from (58Fe) enriched precursors
Previous in vitro studies suggested that gastrointestinal uptake of iron NPs could occur through several mechanisms[13,26,27]

Summary

Introduction

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Our study objectives were: (1) in mouse models, (i) to compare Hb trajectories (iron absorption and utilization) in intestine-specific DMT1 partial knockdown (DMT1int/int) mice and homozygously floxed (DMT1fl/fl) controls fed diets containing FePO4-NP (SSA 98 m2g−1) or FeSO4 (positive reference compound) for 18 days; and (ii) to compare absorption and biodistribution of iron from a single oral dose of F ePO4-NP (SSA 98 m2g−1) and FeSO4 labelled with radioactive iron (59Fe) in iron deficient anemic DMT1int/int and D MT1fl/fl control mice; (2) in iron deficient anemic women, to measure iron absorption and erythrocyte iron utilization (bioavailability) from a rice and vegetable meal fortified with large and small FePO4-NP (SSA 98 m2 g−1 and 188 m2 g−1) labeled with a stable iron isotope (57Fe), compared to 58Fe-labeled bulk F ePO4 and F eSO4 as negative and positive reference compounds, respectively

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Results

Conclusion