{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T22:17:40Z","timestamp":1781821060714,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T00:00:00Z","timestamp":1449100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Arginine octamer (R8) and its derivatives were developed in this study for the enhanced mucosal permeation of insulin. R8 was substituted with different aminos, then modified with stearic acid (SA). We found that the SAR6EW-insulin complex had stronger intermolecular interactions and higher complex stability. The amphiphilic lipopeptide (SAR6EW) was significantly more efficient for the permeation of insulin than R8 and R6EW both in vitro and in vivo. Interestingly, different cellular internalization mechanisms were observed for the complexes. When the effectiveness of the complexes in delivering insulin in vivo was examined, it was found that the SAR6EW-insulin complex provided a significant and sustained (six hours) reduction in the blood glucose levels of diabetic rats. The improved absorption could be the comprehensive result of stronger intermolecular interactions, better enzymatic stability, altered internalization pathways, and increased transportation efficacy. In addition, no sign of toxicity was observed after consecutive administrations of SAR6EW. These results demonstrate that SAR6EW is a promising epithelium permeation enhancer for insulin and suggest that the chemical modification of cell-penetrating peptides is a feasible strategy to enhance their potential.<\/jats:p>","DOI":"10.3390\/molecules201219771","type":"journal-article","created":{"date-parts":[[2015,12,3]],"date-time":"2015-12-03T11:12:09Z","timestamp":1449141129000},"page":"21569-21583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Amphiphilic Lipopeptide-Mediated Transport of Insulin and Cell Membrane Penetration Mechanism"],"prefix":"10.3390","volume":"20","author":[{"given":"Yu","family":"Zhang","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Han","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoyin","family":"Hu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liefeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, 210046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2337\/diacare.27.1.239","article-title":"Concept, strategies, and feasibility of noninvasive insulin delivery","volume":"27","author":"Cefalu","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.addr.2007.08.019","article-title":"Current challenges in non-invasive insulin delivery systems: A comparative review","volume":"59","author":"Khafagy","year":"2007","journal-title":"Adv. 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