Introduction for the special issue on recent advances in drug delivery across tissue barriers.

This special issue of Tissue Barriers contains a series of reviews with the common theme of how biological barriers established at epithelial tissues limit the uptake of macromolecular therapeutics. By improving our functional understanding of these barriers, the majority of the authors have highlighted potential strategies that might be applied to the non-invasive delivery of biopharmaceuticals that would otherwise require an injection format for administration. Half of the articles focus on the potential of particular technologies to assist oral delivery of peptides, proteins and other macromolecules. These include use of prodrug chemistry to improve molecule stability and permeability, and the related potential for oral delivery of poorly permeable agents by cell-penetrating peptides and dendrimers. Safety aspects of intestinal permeation enhancers are discussed, along with the more recent foray into drug-device combinations as represented by intestinal microneedles and externally-applied ultrasound. Other articles highlight the crossover between food research and oral delivery based on nanoparticle technology, while the final one provides a fascinating interpretation of the physiological problems associated with subcutaneous insulin delivery and how inefficient it is at targeting the liver.