The aim of this study was to construct a chitosan quaternary ammonium salt (HTCC)/sodium alginate (SA) nanoparticle delivery system for the encapsulation of Antarctic krill peptide (AKP), with the goal of enhancing its stability and post-digestive hypoglycemic activity. Additionally, the effect of the content and encapsulation sequence of HTCC/SA on the structure and properties of AKP-loaded nanoparticles (AKP-loaded NPs) was investigated. As the content of the outermost wall material (HTCC) increased, the particle size of nanoparticles initially increased and then decreased. Concurrently, the zeta potential showed a trend of increase, ranging from -38.77 to 46.07 mV. When SA was used as the outermost wall material, the nanoparticles exhibited a smaller particle size (240.1 nm) and better dispersibility. Electrostatic interaction and hydrogen bonding were the major forces involved in the formation of AKP-loaded NPs. X-ray diffraction revealed that AKP was successfully encapsulated in an amorphous state. Scanning electron microscopy showed that AKP-loaded NPs had an elliptical or blocky appearance. Moreover, AKP-loaded NPs demonstrated good storage and temperature stability, while nanoparticles with HTCC in the outermost layer (HTCC:SA=2:1) showed good pH and ionic stability. During simulated digestion, AKP-loaded NPs inhibited the release of AKP in gastric fluid. Consequently, the hypoglycemic activity of digested AKP-loaded NPs was remarkably higher than unencapsulated AKP. Notably, the nanoparticles with HTCC in the outermost layer provided superior hypoglycemic activity. In summary, the polysaccharide-based delivery system exhibited great potential to improve the stability and post-digestive hypoglycemic activity of AKP, broadening its applications in the food and pharmaceutical industries.
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