Dairy and nondairy proteins as nano-architecture structures for delivering phenolic compounds: Unraveling their molecular interactions to maximize health benefits.

Phenolic compounds are recognized for their benefits against degenerative diseases. Clinical and nutritional applications are limited by their low solubility, stability, and bioavailability, compromising their efficacy. Natural macromolecules, such as lipids, polysaccharides, and proteins, employed as delivery systems can efficiently overcome these limitations. In this sense, proteins are attractive due to their biocompatibility and dynamic structure properties, functional adaptability and self-assembly capabilities, offering stability, efficient encapsulation, and controlled release. This review explores the potential use of dairy proteins, caseins, and whey proteins, and, alternatively, nondairy proteins, gelatin, human serum albumin, maize zein, and soybean proteins, in building wall materials for the delivery of phenolic compounds. To optimize performance, aspects, such as protein-phenolic affinity and complex stability/activity, should be considered when designing particle nano-architecture. Molecular interactions between protein-phenolic compound complexes are, thus, further discussed, as well as the effects of temperature and pH and strategies to stabilize and preserve nano-architecture and retain phenolic compound activity. All proteins harbor one or more putative binding sites, shared or not, depending on the phenolic compound. Preservation techniques are still a case-to-case study, as no behavior patterns among different complexes are noted. Safety aspects necessary for the marketing of nanoproducts, such as characterization, toxicity assessments, and post-market monitoring as defined by the European Food Safety Authority and the Food and Drug Administration, are discussed, evidencing the need for a unified regulation. This review broadens our understanding and opens new opportunities for the development of novel protein-based nanocarriers to obtain more effective and stable products, enhancing phenolic compound delivery and health benefits.