{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:01:55Z","timestamp":1790503315567,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T00:00:00Z","timestamp":1583971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Seventh Framework Programme","award":["281035"],"award-info":[{"award-number":["281035"]}]},{"DOI":"10.13039\/501100001602","name":"Science Foundation Ireland","doi-asserted-by":"publisher","award":["12\/RC\/2275"],"award-info":[{"award-number":["12\/RC\/2275"]}],"id":[{"id":"10.13039\/501100001602","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The use of nanocarriers is being researched to achieve oral peptide delivery. Insulin-associated anionic polyelectrolyte nanoparticle complexes (PECs) were formed that comprised hyaluronic acid and chitosan in an optimum mass mixing ratio of 5:1 (MR 5), followed by coating with a pH-dependent polymer. Free insulin was separated from PECs by size exclusion chromatography and then measured by HPLC. The association efficiency of insulin in PECs was &gt;95% and the loading was ~83 \u00b5g\/mg particles. Dynamic light scattering and nanoparticle tracking analysis of PECs revealed low polydispersity, a negative zeta potential range of \u221240 to \u221250 mV, and a diameter range of 95\u2013200 nm. Dissolution studies in simulated small intestinal fluid (FaSSIF-V2) revealed that the PECs were colloidally stable. PECs that were coated with Eudragit\u00ae L-100 delayed insulin release in FaSSIF-V2 and protected insulin against pancreatin attack more than uncoated PECs. Uncoated anionic PECs interacted weakly with mucin in vitro and were non-cytotoxic to Caco-2 cells. The coated and uncoated PECs, both concentrated further by ultrafiltration, permitted dosing of 50 IU\/kg in rat jejunal instillations, but they failed to reduce plasma glucose or deliver insulin to the blood. When ad-mixed with the permeation enhancer (PE), sucrose laurate (100 mM), the physicochemical parameters of coated PECs were relatively unchanged, however blood glucose was reduced by 70%. In conclusion, the use of a PE allowed for the PEC-released bioactive insulin to permeate the jejunum. This has implications for the design of orally delivered particles that can release the payload when formulated with enhancers.<\/jats:p>","DOI":"10.3390\/pharmaceutics12030259","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T08:58:59Z","timestamp":1584089939000},"page":"259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations When Combined with a Permeation Enhancer"],"prefix":"10.3390","volume":"12","author":[{"given":"Svenja","family":"Sladek","sequence":"first","affiliation":[{"name":"UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-7950","authenticated-orcid":false,"given":"Fiona","family":"McCartney","sequence":"additional","affiliation":[{"name":"UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mena","family":"Eskander","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Dunne","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7038-5469","authenticated-orcid":false,"given":"Maria Jose","family":"Santos-Martinez","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland"},{"name":"School of Medicine, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6491-4715","authenticated-orcid":false,"given":"Federico","family":"Benetti","sequence":"additional","affiliation":[{"name":"ECSIN Laboratory\u2013Ecamricert Srl, Corso Stati Uniti 4, I-35127 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1544-6796","authenticated-orcid":false,"given":"Lidia","family":"Tajber","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8781-8344","authenticated-orcid":false,"given":"David J.","family":"Brayden","sequence":"additional","affiliation":[{"name":"UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.ijbiomac.2018.08.152","article-title":"Recent advances of polysaccharide-based nanoparticles for oral insulin delivery","volume":"120","author":"Hu","year":"2018","journal-title":"Int. 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