Nanocarriers enhance oral bioavailability: from absorption mechanisms to design strategies

Gastrointestinal barriers (acidic environment, mucus barrier, tight junctions, and microbiota metabolism) have long constrained the oral bioavailability of food-derived bioactives, especially lipophilic constituents. Recent advances in functionalized nanoparticle strategies offer sophisticated techniques to address these challenges. Specifically, precise control of particle size, morphology and surface functionalization enhances mucus penetration and cellular uptake of nanocarriers. Advanced nanocarrier strategies, such as mucosal adhesion, receptor-mediated targeting, and co-delivery with permeation enhancers, facilitate efficient absorption by opening intercellular gaps and activating specific endocytosis pathways. Intelligent designs for pH, enzyme, redox, and microbiome responses resulted in precise protection and targeted release of cargoes in various gastrointestinal segments. This review summarizes critical strategies for absorption-optimized oral nanoplatforms, including absorption mechanisms, mucosal retention, receptor-mediated endocytosis, co-delivery with absorption enhancers, and multi-strategy coupling. We emphasize strategic orientations for maximizing oral absorption efficiency of bioactive ingredients, offering a transformative framework for architecting next-generation oral nanocarrier platforms of food-derived components.