Influence of isochlorogenic acid isomers and stepwise assembly with β-lactoglobulin and hyaluronic acid on constructing a non-covalent ternary carrier for curcumin delivery

A non-covalent ternary carrier (β-Lg/HA/isochlorogenic acid) was constructed for curcumin delivery. • Stepwise assemble and isochlorogenic acid isomer structure critically influence complex properties. • Ternary complex greatly improves curcumin encapsulation efficiency. • Curcumin shows controlled release and enhanced antioxidant activity. Curcumin (Cur) possesses diverse biological activities but has poor water solubility, low stability, and limited bioavailability, which restrict its application. This study aimed to construct a non-covalent ternary complex comprising β-lactoglobulin (β-Lg), isochlorogenic acid, and hyaluronic acid (HA) as an efficient delivery system for Cur. The three isomeric structures of isochlorogenic acid (ICA, ICB, or ICC) and their sequential assemblies (protein–polyphenol–polysaccharide vs. protein–polysaccharide–polyphenol) critically influenced the structural and functional properties of the complexes. The results demonstrated that the protein–polysaccharide–polyphenol assembly sequence, particularly with ICA, yielded superior polyphenol-binding capacity, antioxidant activity, and emulsifying properties. Structural analyses and molecular docking confirmed significant conformational changes in β-Lg and non-covalent interactions increase within the ternary complex. The selected β-Lg–HA–isochlorogenic acid complexes were subsequently used for Cur encapsulation, achieving a high encapsulation efficiency (maximum at 68.78% for β-Lg–HA–ICA–Cur), reduced particle size, and enhanced stability under thermal, centrifugal, freeze-thaw, and storage conditions. The release efficiency of the Cur delivery system was two times higher than free Cur during simulated intestinal digestion. Furthermore, the encapsulated Cur exhibited significantly improved antioxidant activity by over 1.5 times compared with that of free Cur. This study underscores the pivotal role of polyphenol isomeric structures and assembly sequences in the design of functional ternary complexes, providing a promising strategy for developing efficient Cur delivery systems for food applications.