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

Oral drug administration has been a popular choice dueto patientcompliance and limited clinical resources. Orally delivered drugsmust circumvent the harsh gastrointestinal (GI) environment to effectivelyenter the systemic circulation. The GI tract has a number of structuraland physiological barriers that limit drug bioavailability includingmucus, the tightly regulated epithelial layer, immune cells, and associatedvasculature. Nanoparticles have been used to enhance oral bioavailabilityof drugs, as they can act as a shield to the harsh GI environmentand prevent early degradation while also increasing uptake and transportof drugs across the intestinal epithelium. Evidence suggests thatdifferent nanoparticle formulations may be transported via differentintracellular mechanisms to cross the intestinal epithelium. Despitethe existence of a significant body of work on intestinal transportof nanoparticles, many key questions remain: What causes the poorbioavailability of the oral drugs? What factors contribute to theability of a nanoparticle to cross different intestinal barriers?Do nanoparticle properties such as size and charge influence the typeof endocytic pathways taken? In this Review, we summarize the differentcomponents of intestinal barriers and the types of nanoparticles developedfor oral delivery. In particular, we focus on the various intracellularpathways used in nanoparticle internalization and nanoparticle orcargo translocation across the epithelium. Understanding the gut barrier,nanoparticle characteristics, and transport pathways may lead to thedevelopment of more therapeutically useful nanoparticles as drug carriers.