RT Journal Article ID 14ab789a1f4a061b A1 Maher, Sam A1 Brayden, David J. A1 Feighery, Linda A1 McClean, Siobhan T1 Cracking the Junction: Update on the Progress of Gastrointestinal Absorption Enhancement in the Delivery of Poorly Absorbed Drugs JF Critical Reviews™ in Therapeutic Drug Carrier Systems JO CRT YR 2008 FD 2008-05-02 VO 25 IS 2 SP 117 OP 168 AB There are many challenges to the oral delivery of peptide-based drugs. In addition to overcoming issues relating to the metabolic stability of peptides and maximizing adherence and penetration through the mucus layer, new formulations to enhance absorption across the intestinal epithelium are required for effective delivery. The tight junctions between epithelial cells usually permit the flux of small hydrophilic drugs, while restricting the movement of larger hydrophilic drugs. Efforts to reversibly open tight junctions with paracellular permeability enhancers (PPE) have been shown to promote the absorption of larger molecules, including protein therapeutics. This review describes the proteins that comprise the tight junction and outlines various methods that have been explored to enhance class III solute absorption across this barrier, with particular attention to efforts to enhance oral peptide delivery. In particular, peptide-based PPEs are highlighted. Being proteins themselves, they potentially share physicochemical properties, diffusional characteristics, and stability issues with the therapeutic proteins being delivered. By understanding the mechanisms by which these PPEs act, analogues and peptidomimetics can be designed in order to safely enhance the delivery of biotech cargoes via the oral route. PB Begell House LK https://www.dl.begellhouse.com/journals/3667c4ae6e8fd136,56f8b04417929fcd,14ab789a1f4a061b.html