Structural Characteristics of the Gastrointestinal Tract and the Transport Pathways of Peptide Drug Delivery Systems

Peptide drugs show great potential in treating critical diseases, yet their oral delivery faces severe challenges due to multiple physiological barriers in the gastrointestinal tract. To achieve the oral administration of peptide drugs, various oral drug delivery systems such as nanocarriers, ionic liquids, microneedles, and delivery devices have attracted extensive attention; however, the number of products currently approved for marketing is still relatively limited. Clarifying the structural characteristics of the gastrointestinal tract and the transport pathways of drug delivery systems can provide a theoretical basis for the rational design of oral peptide drug formulations. This article systematically summarizes the physiological structure of the gastrointestinal tract as well as the biochemical and physical barriers formed thereby. Focusing on the major pathways by which drug delivery systems penetrate the epithelial barrier, it elaborates on the mechanisms and regulatory strategies of transcellular pathway, paracellular pathway and microfold cell-mediated lymphatic transport pathway. On this basis, it sorts out oral peptide delivery systems designed based on different transport pathways, and summarizes the research trends of achieving targeted delivery to extra-intestinal organs via oral administration, aiming to provide theoretical basis and design strategies for developing high-efficiency oral peptide delivery systems.