pH-Triggered, Synbiotic Hydrogel Beads for <i>In Vivo</i> Therapy of Iron Deficiency Anemia and Reduced Inflammatory Response

Abstract

Iron deficiency anemia (IDA) is the most common nutritional disorder worldwide nearly affecting two billion people. The efficacies of conventional oral iron supplements are mixed, intravenous iron administration acquaintances with finite but crucial risks. Usually, only 5-20% iron is absorbed in the duodenum while the remaining fraction reaches the colon, affecting the gut microbes and can significantly impact intestinal inflammatory responses. Therefore, administration of gut bacterial modulators such as probiotics, prebiotics, and any other dietary molecules that can stimulate healthy gut bacteria can enhance iron absorption without any adverse side effects. In this study, we have prepared an iron supplement to avoid the side effects of conventional oral iron supplements. The formulation includes co-encapsulation of iron with anti-inflammatory probiotic bacteria within alginate/starch hydrogels (B + I-Dex (H)), which has been demonstrated to be efficient in mitigating IDA <i>in vivo</i>. As intestinal pH increases, the pore size of hydrogel increases due to ionic interactions and thus releases the encapsulated bacteria and iron. The field emission scanning electron microscopy (FESEM) analysis confirmed the porous structure of hydrogel beads, and <i>in vitro</i> release studies showed a sustained release of iron and bacteria at intestinal pH. The hydrogel was found to be nontoxic and biocompatible in Caco2 cell lines. The formulation showed efficient <i>in vitro</i> and <i>in vivo</i> iron bioavailability in Fe depletion-repletion studies. B + I-Dex (H) was observed to generate less inflammatory response than FeSO₄ or nonencapsulated iron dextran (I-Dex) <i>in vivo</i>. We entrust that this duly functional hydrogel formulation could be further utilized or modified for the development of oral therapeutics for IDA.