Nanostructure-Mediated Transport of Therapeutics through Epithelial Barriers

Abstract

The ability to precisely treat human disease is facilitated by the sophisticated design of pharmacologic agents. Nanotechnology has emerged as a valuable approach to creating vehicles that can specifically target organ systems, effectively traverse epithelial barriers, and protect agents from premature degradation. In this review, we discuss the molecular basis for epithelial barrier function, focusing on tight junctions, and describe different pathways that drugs can use to cross barrier-forming tissue, including the paracellular route and transcytosis. Unique features of drug delivery applied to different organ systems are addressed: transdermal, ocular, pulmonary, and oral delivery. We also discuss how design elements of different nanoscale systems, such as composition and nanostructured architecture, can be used to specifically enhance transepithelial delivery. The ability to tailor nanoscale drug delivery vehicles to leverage epithelial barrier biology is an emerging theme in the pursuit of facilitating the efficacious delivery of pharmacologic agents.