Intestinal-specific oral delivery of lactoferrin with alginate-based composite and hybrid CaCO₃-hydrogel beads

Sodium alginate hydrogel beads and sodium alginate/gellan gum composite hydrogel beads crosslinked by calcium chloride were prepared with different alginate concentrations (3-20 mg·mL^-1). Additionally, a simple method for growing CaCO₃in situ on the hydrogel to create novel inorganic-organic hybrid hydrogel beads was presented. FT-IR analysis revealed the involvement of hydrogen bonding and electrostatic interactions in bead formation. Swelling behavior in acidic conditions showed a maximum of 13 g/g for composite hydrogels and CaCO₃-incorporated hybrid hydrogels. Lactoferrin encapsulation efficiency within these hydrogels ranged from 44.9 to 56.6%. In vitro release experiments demonstrated that these hydrogel beads withstand harsh gastric environments with <16% cumulative release of lactoferrin, achieving controlled release in intestinal surroundings. While composite sodium alginate/gellan gum beads exhibited slower gastrointestinal lactoferrin digestion, facile synthesis and pH responsiveness of CaCO₃-incorporated hybrid hydrogel also provide new possibilities for future studies to construct a novel inorganic-organic synergetic system for intestinal-specific oral delivery.