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Δευτέρα 12 Φεβρουαρίου 2018

Oral delivery of anti-diabetes therapeutics using cell penetrating and transcytosing peptide strategies

Publication date: February 2018
Source:Peptides, Volume 100
Author(s): Sahrish Rehmani, James E. Dixon
Oral delivery of insulin and other anti-diabetic peptides is inhibited by low intestinal absorption caused by the poor permeability across cellular membranes and the susceptibility to enzymatic degradation in the gastrointestinal tract. Cell-penetrating peptides (CPPs) have been investigated for a number of years as oral absorption enhancers for hydrophilic macromolecules by electrostatic or covalent conjugation on in conjunction with nanotechnology. Endogenous cellular uptake mechanisms present in the intestine can be exploited by engineering peptide conjugates that transcytose; entering cells by endocytosis and leaving by exocytosis. Efficiently delivering hydrophilic and sensitive peptide drugs to safely transverse the digestive barrier with no effect on gut physiology using remains a key driver for formulation research. Here we review the use of CPP and transcytosis peptide approaches, their modification and use in delivering anti-diabetic peptides (with the primary example of Insulin and engineered homologues) by direct oral administration to treat diabetes and associated metabolic disorders.



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