Gum Arabic-Stabilized Ferric Oxyhydroxide Nanoparticles for Efficient and Targeted Intestinal Delivery of Bioavailable Iron

Nanostructured iron(III) compounds are promising food fortificants with desirable iron bioavailability and food compatibility. Here, gum arabic (GA) solubilized 252 mg of iron(III) per g at neutral pH in the form of GA-stabilized ferric oxyhydroxide nanoparticles (GA-FeONPs) with Z-average size of 142.7 ± 5.9 nm and ζ-potential of -20.50 ± 1.25 mV. Calcein-fluorescence-quenching assay revealed well-absorbed iron from GA-FeONPs by polarized Caco-2 cells due to efficient macropinocytic internalization and asialoglycoprotein receptor-mediated specific endocytosis facilitated by the polypeptide and arabinogalactan fractions of GA, respectively, with endocytosed GA-FeONPs being in part basolaterally transcytosed and in another part degraded into cellular labile iron pool. GA-FeONPs showed good colloidal stability under varied pH, gastrointestinal, thermal processing, and spray/freeze drying conditions and displayed remarkably weaker pro-oxidant activity than FeSO4 in glyceryl trilinoleate emulsion (P < 0.05). Oral pharmacokinetics unveiled desirable iron bioavailability of GA-FeONPs relative to FeSO4, i.e., 124.27 ± 5.91% in aqueous solution and 161.64 ± 5.01% in milk. Overall, GA-FeONPs are a promising novel iron fortificant with food-compatible, efficient, and targeted intestinal iron delivery and sustained iron-release properties.