dc.contributor.author | Tajber, Lidia | |
dc.contributor.author | Sladek, Svenja | |
dc.contributor.author | McCartney, Fiona | |
dc.contributor.author | Eskander, Mena | |
dc.contributor.author | Dunne, David J. | |
dc.contributor.author | Santos-Martinez, Maria Jose | |
dc.contributor.author | Benetti, Federico | |
dc.contributor.author | Brayden, David J. | |
dc.date.accessioned | 2020-06-08T08:32:11Z | |
dc.date.available | 2020-06-08T08:32:11Z | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020 | en |
dc.identifier.citation | Sladek, S., McCartney, F., Eskander, M., Dunne, D.J., Santos-Martinez, M.J., Benetti, F., Tajber, L. & Brayden, D.J., An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a Permeation Enhancer., Pharmaceutics, 12, 3, 2020 | en |
dc.identifier.issn | 1999-4923 | |
dc.identifier.other | Y | |
dc.identifier.uri | https://www.mdpi.com/1999-4923/12/3/259 | |
dc.identifier.uri | http://hdl.handle.net/2262/92740 | |
dc.description | PUBLISHED | en |
dc.description.abstract | 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 >95% and the loading was ~83 µg/mg particles. Dynamic light scattering and nanoparticle tracking analysis of PECs revealed low polydispersity, a negative zeta potential range of −40 to −50 mV, and a diameter range of 95–200 nm. Dissolution studies in simulated small intestinal fluid (FaSSIF-V2) revealed that the PECs were colloidally stable. PECs that were coated with Eudragit® 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. | en |
dc.description.sponsorship | European TRANS-INT Consortium, the European Union’s 7th Framework Programme, grant agreement No. 281035;
Science Foundation Ireland (SFI) with additional support from the European Regional Development Fund, Synthesis and Solid State Pharmaceutical Centre (SSPC), grant number 12/RC/2275. | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Pharmaceutics; | |
dc.relation.ispartofseries | 12; | |
dc.relation.ispartofseries | 3; | |
dc.rights | Y | en |
dc.subject | Insulin | en |
dc.subject | Hylauronic acid | en |
dc.subject | Chitosan | en |
dc.subject | Oral peptide delivery | en |
dc.subject | Intestinal permeation enhancers | en |
dc.subject | Nanomedicine | en |
dc.title | An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a Permeation Enhancer | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/ltajber | |
dc.identifier.rssinternalid | 216133 | |
dc.identifier.doi | http://dx.doi.org/10.3390/pharmaceutics12030259 | |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.subject.TCDTheme | Nanoscience & Materials | en |
dc.identifier.orcid_id | 0000-0003-1544-6796 | |