Hyaluronic Acid Hydrogel-Based Oral Delivery of Iron Supplemented with Probiotic and Prebiotic Ameliorates Iron-Deficiency Anaemia

The oral iron supplementation leads to gut dysbiosis, further activating intestinal inflammatory response leading to inflammatory bowel syndrome. Iron salt supplementation combined with synbiotics has become an effective strategy to tackle gut health with iron-deficiency anaemia. Progressing toward targeted and sustained release of oral drug delivery, in this work, we have developed thiolated-hyaluronic acid encapsulated synbiotic hydrogel (HASH + BIDF) comprising iron dextran (ID), soluble millet dietary fiber (DF), and probiotic <i>Lactobacillus rhamnosus</i> (<i>LR</i>). The consumption of developed HASH + BIDF was able to recover the hemoglobin (Hb) levels among diet-induced anemic mice (Hb ∼ 9.5) in a treatment period of 2 weeks (Hb ∼ 14.4). In vivo conditions marked recovery of iron marker mRNA levels. DMT-1 from ∼11.13-fold change in anemic to 0.25-fold change after HASH + BIDF treatment, and DcytB expression change from ∼50.96-fold expression under anemic conditions to ∼0.3-fold in the HASH + BIDF supplemented group were observed. Estimating the ferritin protein expression provided significant enhancement in HASH + BIDF indicating replenishment of metabolic iron stores with oral formulation. Lowered expression of TNF-α and IL-6 in intestinal tissues in both Western blotting and immunofluorescence after treatment with HASH + BIDF indicated the anti-inflammatory response of the prepared formulation. The findings suggested a step toward the development of an integrated oral iron supplementation medium with improved bioavailability and reduced gut inflammation.