Synergistic role of quercetin in sodium alginate/κ-carrageenan hydrogel microspheres for the protection and controlled release of the novel antimicrobial peptide hz-01.

To address the poor stability and high susceptibility to degradation of antimicrobial peptides, a pH-responsive hydrogel microsphere system was developed based on sodium alginate (SA) and κ-carrageenan (Car), with quercetin (Que) for intestinal delivery of chemically synthesized free hz-01 peptide. The optimized formulation containing 0.45% Car exhibited the highest encapsulation efficiency (77%), corresponding to an absolute increase of 13 percentage points compared with the system without Que. The microspheres remained stable under simulated gastric conditions but enabled controlled intestinal release, with release kinetics fitting the Korsmeyer-Peppas model (R2 = 0.995), while significantly preserving antimicrobial activity during digestion. Molecular dynamics simulations suggested that hydrogen bonding, electrostatic interactions, and weak hydrophobic associations may contribute to the local stabilization of hz-01 within the SA/Car/Que. matrix. This work provides a food-grade polyphenol-assisted encapsulation strategy in which Que. functions as an auxiliary structural mediator to improve peptide encapsulation, gastric protection, and intestinal-stage release.