Lysozyme as a protein-based carrier for bioactives: advances in delivery systems and gut environment interactions

Background: Bioactive compounds in foods and nutrition-oriented products often exhibit limited intestinal bioaccessibility due to processing stresses and premature degradation or non-specific release during gastrointestinal transit. Food-grade protein carriers are therefore required to protect labile actives and enable controlled, site adapted delivery. Lysozyme (EC 3.2.1.17), characterized by a disulfide bond–stabilized structure and strong cationic nature, has recently gained attention as a functional building block for protein-based delivery systems, while retaining intrinsic biological activity.
Scope and approach: This review systematically examines lysozyme-based protein delivery systems with a focus on how gastrointestinal environmental factors induce structural remodelling and, in turn, regulate loading stability, release behavior, and intestinal bioaccessibility. By integrating evidence across charge-driven complexes and coacervates, nano- and microparticles, Pickering emulsions, hydrogels, fibrillar or tubular assemblies, and film-based systems, the review elucidates how differences in assembly pathways and interfacial organization translate into divergent delivery outcomes. Particular emphasis is placed on the roles of pH gradients, ionic strength, digestive enzymes, bile salts, mucus interactions, and microbiota-associated effects in reshaping lysozyme assemblies, modulating carrier–mucus interactions, and ultimately determining intestinal retention, transport, and bioactive exposure. On this basis, strategies such as polysaccharide/protein co-assembly, interfacial engineering, regulation of self-assembly, and chemical or enzymatic modification are synthesized as rational approaches to directionally optimize gastrointestinal delivery performance. Key findings and conclusions: Evidence indicates that lysozyme enables diverse delivery structures through electrostatic complexation, interfacial stabilization, and self-assembly, thereby enhancing protection of bioactives and supporting controlled intestinal release. Importantly, gastrointestinal factors actively remodel lysozyme assemblies, while interactions with the mucus layer critically determine retention, penetration, and bioaccessibility, representing an emerging design focus. Remaining challenges include gastrointestinal degradation,
performance variability across food matrices and processing conditions, allergenicity and regulatory constraints, and the lack of quantitative evaluation frameworks. Overall, lysozyme represents a promising, designable protein carrier for intestinal-oriented delivery in functional foods.