A comprehensive review of protein-based carriers with simple structures for the co-encapsulation of bioactive agents.

The rational design and fabrication of edible codelivery carriers are important to develop functional foods fortified with a plurality of bioactive agents, which may produce synergistic effects in increasing bioactivity and functionality to target specific health benefits. Food proteins possess considerable functional attributes that make them suitable for the delivery of a single bioactive agent in a wide range of platforms. Among the different types of protein-based carriers, protein-ligand nanocomplexes, micro/nanoparticles, and oil-in-water (O/W) emulsions have increasingly attracted attention in the codelivery of multiple bioactive agents, due to the simple and convenient preparation procedure, high stability, matrix compatibility, and dosage flexibility. However, the successful codelivery of bioactive agents with diverse physicochemical properties by using these simple-structure carriers is a daunting task. In this review, some effective strategies such as combined functional properties of proteins, self-assembly, composite, layer-by-layer, and interfacial engineering are introduced to redesign the carrier structure and explore the encapsulation of multiple bioactive agents. It then highlights success stories and challenges in the co-encapsulation of multiple bioactive agents within protein-based carriers with a simple structure. The partition, protection, and release of bioactive agents in these protein-based codelivery carriers are considered and discussed. Finally, safety and application as well as challenges of co-encapsulated bioactive agents in the food industry are also discussed. This work provides a state-of-the-art overview of protein-based particles and O/W emulsions in co-encapsulating bioactive agents, which is essential for the design and development of novel functional foods containing multiple bioactive agents.