Comparative study of cross-linking strategies for β-lactoglobulin-hyaluronic acid-neochlorogenic acid ternary complexes: Structural characteristics and functional implications for curcumin delivery

To elucidate the effects of different cross-linking methods on the structural and functional properties of ternary complexes, this study systematically engineered β-lactoglobulin-hyaluronic acid-neochlorogenic acid (β-Lg-HA-3CQA) complexes using six distinct strategies: non-covalent cross-linking, ultrasonic-assisted treatment, enzymatic grafting, free radical cross-linking, genipin conjugation, and the Maillard reaction. Structural and functional analyses demonstrated that covalent strategies, significantly outperformed non-covalent and ultrasonic treatment in terms of structural integrity and functional efficacy. Notably, the Maillard-enzymatic approach exhibited the optimal performance, with a solubility of 93.71 %, 3CQA binding content of 73.05 μg/mL, and curcumin entrapment efficiency of 86.55 %. It also significantly enhanced the system stability, as well as its thermal and environmental tolerance. In contrast, ultrasonic treatment offered only transient improvements in dispersion and failed to overcome the intrinsic structural instability of non-covalent complexes. This systematic comparison of multiple cross-linking methods provides both a theoretical framework and practical foundation for optimizing the protein-polysaccharide-polyphenol complexes, thereby enhancing their functional properties and broadening their applicability in food and pharmaceutical fields.