Abstract
Improving the stability of drugs in the gastrointestinal tract and their penetration ability in the mucosal layer by implementing a nanoparticle delivery strategy is currently a research focus in the pharmaceutical field. However, for most drugs, nanoparticles failed in enhancing their oral absorption on a large scale (4 folds or above), which hinders their clinical application. Recently, several researchers have proved that the intestinal epithelial cell membrane crossing behaviors of nanoparticles deeply influenced their oral absorption, and relevant reviews were rare. In this paper, we systematically review the behaviors of nanoparticles in the intestinal epithelial cell membrane and mainly focus on their intracellular mechanism. The three key complex intracellular processes of nanoparticles are described: uptake by intestinal epithelial cells on the apical side, intracellular transport and basal side exocytosis. We believe that this review will help scientists understand the in vivo performance of nanoparticles in the intestinal epithelial cell membrane and assist in the design of novel strategies for further improving the bioavailability of nanoparticles.