Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans

Abstract

Iron deficiency is the most common nutritional disorder worldwide with substantial impact on health and economy. Current treatments predominantly rely on soluble iron which adversely affects the gastrointestinal tract. We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents. Nano Fe(III) absorption in humans correlated with serum iron increase ( P < 0.0001) and direct in vitro cellular uptake ( P = 0.001), but not with gastric solubility. The most promising preparation (iron hydroxide adipate tartrate: IHAT) showed ~80% relative bioavailability to Fe(II) sulfate in humans and, in a rodent model, IHAT was equivalent to Fe(II) sulfate at repleting haemoglobin. Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota. In cellular models, IHAT was 14-fold less toxic than Fe(II) sulfate/ascorbate. Nano Fe(III) manifests minimal acute intestinal toxicity in cellular and murine models and shows efficacy at treating iron deficiency anaemia.

From the Clinical Editor

This paper reports the development of novel nano-Fe(III) formulations, with the goal of achieving a magnitude less intestinal toxicity and excellent bioavailability in the treatment of iron deficiency anemia. Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition.

Graphical Abstract

Current oral treatment of iron deficiency anaemia is based upon soluble iron compounds, all of which have undesirable gastrointestinal effects. However, natural dietary iron (III) may be nano-formed ligand-modified iron hydroxide particles that are acquired endocytically and thus not soluble or available for adverse effects. Here, a series of five different nano Fe(III) hydroxide particles was developed: absorption in humans matched endocytic uptake by gut epithelial cells but not solubility in (stomach) acid. In murine and cellular models nano iron(III) treated iron deficiency anaemia as well as ferrous sulfate but, unlike the latter, was safe to the gut environment.