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Current treatment of this disease involves the intradermal injection of insulin analogues. Many alternative administration routes have been proposed, the oral route being the most widely studied. One of the most interesting approaches for insulin delivery is the use of permeation enhancers to increase its transport across the gastrointestinal tract (GIT). Cell\u2010penetrating peptides (CPPs) are a remarkable example of this family of compounds. Another alternative is the use of medium\u2010chain fatty acids (MCFAs) to temporally disrupt the tight junctions of the GIT, thereby allowing greater drug transport. A combination of both strategies can provide a synergistic way to increase drug transport through the GIT. In this study we evaluated the complexation of insulin glulisine, an insulin analogue administered subcutaneously or intravenously in clinical practice, with a well\u2010known CPP modified with the MCFA lauric acid. We prepared several formulations, examined their stability, and tested the best candidates in an intestinal cell\u2010based model. In particular, two compounds (C<jats:sub>12<\/jats:sub>\u2010r<jats:sub>4<\/jats:sub> and C<jats:sub>12<\/jats:sub>\u2010r<jats:sub>6<\/jats:sub>) were found to significantly increase the transport of insulin, and therefore show promise as a new delivery system worthy of further evaluation.<\/jats:p>","DOI":"10.1002\/cmdc.201800428","type":"journal-article","created":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T19:30:40Z","timestamp":1533065440000},"page":"2045-2052","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["<scp>d<\/scp>\u2010Polyarginine Lipopeptides as Intestinal Permeation Enhancers"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2929-7018","authenticated-orcid":false,"given":"Josep","family":"Garcia","sequence":"first","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Baldiri Reixac 10 08028 Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Fern\u00e1ndez\u2010Blanco","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Baldiri Reixac 10 08028 Barcelona Spain"},{"name":"Cellular &amp; Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation (CRG) The Barcelona Institute of Science and Technology  Dr. Aiguader 88 08003 Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7825-3695","authenticated-orcid":false,"given":"Meritxell","family":"Teixid\u00f3","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Baldiri Reixac 10 08028 Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0159-2381","authenticated-orcid":false,"given":"Macarena","family":"S\u00e1nchez\u2010Navarro","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Baldiri Reixac 10 08028 Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8381-1797","authenticated-orcid":false,"given":"Ernest","family":"Giralt","sequence":"additional","affiliation":[{"name":"Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology (BIST)  Baldiri Reixac 10 08028 Barcelona Spain"},{"name":"University of Barcelona Department of Inorganic and Organic Chemistry  Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,20]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.2165\/00128071-200304100-00001","volume":"4","author":"Richardson T.","year":"2003","journal-title":"Am. 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