An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a Permeation Enhancer
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Title: | An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a Permeation Enhancer | Authors: | Sladek, Svenja; McCartney, Fiona; Eskander, Mena; Brayden, David James; et al. | Permanent link: | http://hdl.handle.net/10197/11785 | Date: | 12-Mar-2020 | Online since: | 2020-12-08T10:57:15Z | 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. | Funding Details: | European Commission - Seventh Framework Programme (FP7) Science Foundation Ireland |
Type of material: | Journal Article | Publisher: | MDPI | Journal: | Pharmaceutics | Volume: | 12 | Issue: | 3 | Copyright (published version): | 2020 the Authors | Keywords: | Bioengineering; Nanotechnology; Insulin; Hyaluronic acid; Chitosan; Oral peptide delivery; Intestinal permeation enhancers; Nanomedicine | DOI: | 10.3390/pharmaceutics12030259 | Language: | en | Status of Item: | Peer reviewed | ISSN: | 1999-4923 | This item is made available under a Creative Commons License: | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ |
Appears in Collections: | Conway Institute Research Collection Veterinary Medicine Research Collection |
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