An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a Permeation Enhancer

Files in This Item:
File Description SizeFormat 
pharmaceutics-12-00259-v2 (1).pdf8.45 MBAdobe PDFDownload
Title: An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a Permeation Enhancer
Authors: Sladek, SvenjaMcCartney, FionaEskander, MenaBrayden, David Jameset 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: BioengineeringNanotechnologyInsulinHyaluronic acidChitosanOral peptide deliveryIntestinal permeation enhancersNanomedicine
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

Show full item record

Page view(s)

157
Last Week
5
Last month
checked on Jan 27, 2021

Download(s)

35
checked on Jan 27, 2021

Google ScholarTM

Check

Altmetric


If you are a publisher or author and have copyright concerns for any item, please email research.repository@ucd.ie and the item will be withdrawn immediately. The author or person responsible for depositing the article will be contacted within one business day.