Aguirre, Tanira A. S.Tanira A. S.AguirreTeijeiro-Osorio, D.D.Teijeiro-OsorioRosa, MónicaMónicaRosaBrayden, David JamesDavid JamesBraydenet al.2016-08-192017-02-242016 Elsev2016-11-15Advanced Drug Delivery Reviewshttp://hdl.handle.net/10197/7801The development of oral dosage forms that allows absorption of therapeutic peptides to the systemic circulation is one of the greatest challenges for the pharmaceutical industry. Currently, a number of technologies including either mixtures of penetration enhancers or protease inhibitors and/or nanotechnology-based products are under clinical development. Typically, these formulations are presented in the form of enteric-coated tablets or capsules. Systems undergoing preclinical investigation include further advances in nanotechnology, including intestinal microneedle patches, as well as their combination with regional delivery to the colon. This review critically examines four selected promising oral peptide technologies at preclinical stage and the twelve that have progressed to clinical trials, as indicated in www.clinicaltrials.gov. We examined these technologies under the criteria of peptide selection, formulation design, system components and excipients, intestinal mechanism of action, efficacy in man, and safety issues. The conclusion is that most of the technologies in clinical trials are incremental rather than paradigm-shifting and that even the more clinically-advanced oral peptide drugs examples of oral bioavailability appear to yield oral bioavailability values of only 1-2% and are, therefore, only currently suitable for a limited range of peptides.enThis is the author’s version of a work that was accepted for publication in Advanced Drug Delivery Reviews. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Advanced Drug Delivery Reviews (106, Part B, (2016)) https://doi.org/10.1016/j.addr.2016.02.0044.Oral peptidesIntestinal permeation enhancersTherapeutic peptidesPeptide clinical trialsOral nanotechnologyJournal Article106Part B10.1016/j.addr.2016.02.0042016-07-27https://creativecommons.org/licenses/by-nc-nd/3.0/ie/