期刊
PEPTIDES
卷 100, 期 -, 页码 24-35出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2017.12.014
关键词
Oral drug delivery; Peptide drugs; Nanoparticles; Cell penetrating peptides; Peptide permeability; Bioavailability; Human intestinal tissue; Transcytosis; Transepithelial transport
资金
- European Research Council under the European Community's Seventh Framework Programme (FP7)/ERC [227845]
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council UK Regenerative Medicine Platform Hub Acellular Approaches for Therapeutic Delivery [MR/K026682/1]
- Punjab Educational Endowment Fund (PEEF) scholarship, Government of Punjab, Pakistan
- MRC [MR/K026682/1] Funding Source: UKRI
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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