Structure and Function of the Intercellular Junctions: Barrier of Paracellular Drug Delivery

The delivery of large hydrophilic molecules (i.e., peptides and proteins) across biological barriers has been hampered by the presence of tight junctions. This delivery process can be improved by enhancing permeation through intercellular junctions of the intestinal mucosa and blood-brain barriers. This is achieved by modulating the intercellular junctions of these biological barriers. To modulate intercellular junctions, it is necessary to understand the structure and function of the proteins that are involved in these junctions. This review focuses on the structure of intercellular junctions and possible mechanisms of intercellular junction formation. Modulation of protein-protein interactions has been shown to increase the porosity of the paracellular pathway. For example, E-cadherin derived peptides have been shown to enhance the permeation of hydrophilic molecules (i.e., mannitol) in cell culture models of biological barriers.