pH-Responsive Sustained-Release Hydrogel Microspheres for the Protection, Delivery and Release of Oral Polysaccharide Iron

Oral administration of polysaccharide-iron complexes (UCP-Fe(III)) is limited by their degradation in the gastric environment, which reduces bioavailability. We developed core-shell sodium alginate/chitosan hydrogel microsphere for pH-responsive UCP-Fe(III) delivery. High sodium alginate (SA) concentrations increased viscosity and storage modulus, enhancing mechanical stability. The encapsulation efficiency of UCP-Fe(III) reached 94.41% using 2.0% SA. Noncovalent interactions between UCP-Fe(III) and SA contributed to enhanced hardness and chewiness of the microspheres, while higher SA concentrations promoted a denser cross-linked network. The hydrogel microspheres showed low swelling in simulated gastric fluid (SGF, pH 2.0; swelling ratio: 467.33-588.50%) but rapid swelling in simulated intestinal fluid (SIF, pH 7.4; swelling ratio: 800-962.17%), indicating significant pH responsiveness. They effectively prevented premature release (only 12.14-23.48% in SGF after 2 h) while enabling sustained release (87.60-95.16% in SIF after 6 h). This study provides a new strategy for developing oral iron supplements with pH-responsive sustained-release properties.