Mechanisms of Nanoparticle Transport across Intestinal Tissue: An Oral Delivery Perspective

Oral drug administration has been a popular choice due to patient compliance and limited clinical resources. Orally delivered drugs must circumvent the harsh gastrointestinal (GI) environment to effectively enter the systemic circulation. The GI tract has a number of structural and physiological barriers that limit drug bioavailability including mucus, the tightly regulated epithelial layer, immune cells, and associated vasculature. Nanoparticles have been used to enhance oral bioavailability of drugs, as they can act as a shield to the harsh GI environment and prevent early degradation while also increasing uptake and transport of drugs across the intestinal epithelium. Evidence suggests that different nanoparticle formulations may be transported via different intracellular mechanisms to cross the intestinal epithelium. Despite the existence of a significant body of work on intestinal transport of nanoparticles, many key questions remain: What causes the poor bioavailability of the oral drugs? What factors contribute to the ability of a nanoparticle to cross different intestinal barriers? Do nanoparticle properties such as size and charge influence the type of endocytic pathways taken? In this Review, we summarize the different components of intestinal barriers and the types of nanoparticles developed for oral delivery. In particular, we focus on the various intracellular pathways used in nanoparticle internalization and nanoparticle or cargo translocation across the epithelium. Understanding the gut barrier, nanoparticle characteristics, and transport pathways may lead to the development of more therapeutically useful nanoparticles as drug carriers.