Core-shell hydrogel beads co-encapsulating kunitz-type trypsin inhibitor: A synergistic strategy for enhanced...

This study repurposed Kunitz-type trypsin inhibitor (KTI) as a synergistic component for oral peptide co-delivery to overcome the burst release and enzymatic degradation of liraglutide. A pH-responsive chitosan (CS)‑sodium alginate (ALG) core-shell hydrogel co-delivery system co-encapsulating KTI and liraglutide, named ACKL (ALG-CS-KTI-liraglutide), was accordingly constructed. The optimized microspheres, with a 3% sodium tripolyphosphate (TPP)-crosslinked core and 0.8% ALG shell, exhibited uniform morphology, a distinct core-shell structure, and excellent mechanical properties. Molecular docking and Fourier transform infrared spectroscopy (FTIR) confirmed that KTI and liraglutide bind via hydrophobic interactions without compromising KTI's active center. Achieving high encapsulation efficiencies (liraglutide >95%, KTI > 75%), the beads exhibited a release rate below 8% in simulated gastric fluid (SGF) and sustained liraglutide release in simulated intestinal fluid (SIF). Therefore, this work provides a new strategy for oral delivery of bioactive peptides, opening a new avenue for the high-value utilization of soybean by-products in functional food and nutraceutical applications.