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Critical Reviews™ in Therapeutic Drug Carrier Systems
IF: 2.9 5-Year IF: 3.72 SJR: 0.736 SNIP: 0.551 CiteScore™: 2.43

ISSN Print: 0743-4863
ISSN Online: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v25.i2.10
pages 117-168

Cracking the Junction: Update on the Progress of Gastrointestinal Absorption Enhancement in the Delivery of Poorly Absorbed Drugs

Sam Maher
UCD Conway Institute and UCD School of Agriculture, Food Science and Veterinary Medicine, UCD, Belfield, Dublin 4, Ireland
David J. Brayden
UCD Conway Institute and UCD School of Agriculture, Food Science and Veterinary Medicine, UCD, Belfield, Dublin 4, Ireland
Linda Feighery
UCD Conway Institute and UCD School of Agriculture, Food Science and Veterinary Medicine, UCD, Belfield, Dublin 4, Ireland
Siobhan McClean
Institute of Technology Tallaght Dublin (ITT Dublin) and National Institute of Cellular Biotechnology, Old Blessington Road, Tallaght, Dublin 24, Ireland

ABSTRACT

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.


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