Formation mechanisms, fabrication strategies, and applications of casein-polyphenol complexes

Polyphenols are bioactive compounds with a variety of health-promoting properties, but their environmental sensitivity and low bioavailability limit their application in food and pharmaceutical systems. Encapsulation strategies have therefore been developed to improve their stability and functionality, among which casein-based systems have attracted considerable interest due to the structural flexibility of caseins and their strong affinity for phenolic compounds. This review summarizes recent advances in the development and characterization of casein-polyphenol conjugates, highlighting their improved antioxidant activity, thermal stability, and emulsifying performance compared with native caseins. Interactions between caseins and polyphenols induce conformational modifications that increase molecular flexibility and broaden functional properties. Covalent interactions generally produce more stable complexes, whereas non-covalent interactions allow reversible binding suitable for controlled delivery applications. Conjugate formation not only protects polyphenols from degradation during processing and storage but also enhances their stability and bioavailability during gastrointestinal digestion. The functional characteristics of both caseins and polyphenols are also modulated through conjugation, enabling their application in micellar systems, emulsions, and other delivery platforms. Advances in analytical techniques have facilitated detailed evaluation of binding mechanisms, structural changes, and functional outcomes. Despite promising progress, challenges remain in large-scale production, functional consistency, and formulation optimization, and addressing these issues will support the broader industrial application of casein-based delivery systems for functional food and bioactive compound development. © 2026 Society of Chemical Industry.