Oral delivery of Pickering emulsions to gastrointestinal tract: Multiscale interaction, intelligent targeting and therapeutic mechanism.

The gastrointestinal tract is the primary site for human digestion and absorption, where bioactive compounds are taken up and transformed. Its complex physiological barriers pose multiple challenges to the efficiency and precision of oral delivery. Pickering emulsions (PEs) stabilized by micro/nano-scale solid particles have emerged as a promising strategy for specific gastrointestinal delivery due to versatile material selection, superior interfacial stability, tunability across multiple scales, and various response behaviors. This review systematically elucidates that the multiscale structural design of PEs across molecular, microscopic, mesoscopic, and macroscopic levels regulates their interactions with mucosal epithelial barriers in the stomach, small intestine, and colon. The multiscale design principles, intelligent targeting strategies, and therapeutic mechanisms are connected to develop PEs tailored to the physical, chemical, biological, and immunological properties of mucosal epithelial barriers. This enables stable delivery of PEs in the harsh gastrointestinal environment, achieving precise targeting, controlled release, and effective treatment. This review aims to provide a theoretical foundation for developing PEs with specific gastrointestinal delivery, therefore promoting their application in nutritional interventions and disease treatments.