Oral Delivery Systems for Food-Derived Bioactive Peptides: Enhancing Stability, Bioavailability, and Health Benefits

Food-derived bioactive peptides (FBPs) represent a promising class of nutraceuticals for the prevention and management of chronic diseases due to their diverse bioactivities and high biocompatibility; however, their therapeutic potential is severely limited by low oral bioavailability resulting from instability during processing, sensory drawbacks such as bitterness, and extensive gastrointestinal degradation. This review systematically outlines the major bottlenecks hindering the oral delivery of FBPs, including sensitivity to environmental factors (temperature, pH, metal ions) and physiological barriers (enzymatic hydrolysis, mucus layer, and epithelial transport). To overcome these challenges, advanced delivery systems, such as nanoparticles (NPs), nanoemulsions (NEs), liposomes, hydrogels, and composite carriers, have been designed. These engineered systems have demonstrated enhanced bioactivity and targeted delivery in preclinical models of neuroprotection, anti-inflammatory therapy, metabolic regulation, and cancer treatment, often outperforming free peptides in terms of stability and intestinal absorption. However, establishing quantitative correlations between formulation parameters and in vivo peptide bioavailability remains a critical bottleneck. Future research should focus on rationally designed stimuli-responsive platforms grounded in intestinal physiology, supported by standardized frameworks for scalable manufacturing and safety evaluation. This work provides a comprehensive framework for advancing FBPs delivery platforms toward functional food and chronic disease management applications.