Type

Journal Article

Authors

David J Brayden
Federico Benetti
Maria-Jose Santos-Martinez
David J. Dunne
Mena Eskander
Fiona McCartney
Svenja Sladek
Lidia Tajber

Subjects

Veterinary

Topics
nanoscience materials hylauronic acid chitosan insulin nanomedicine immunology inflammation infection oral peptide delivery intestinal permeation enhancers

An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin in Rat Intestinal Instillations when Combined with a Permeation Enhancer (2020)

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.
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Full list of authors on original publication

David J Brayden, Federico Benetti, Maria-Jose Santos-Martinez, David J. Dunne, Mena Eskander, Fiona McCartney, Svenja Sladek, Lidia Tajber

Experts in our system

1
David J Brayden
University College Dublin
Total Publications: 97
 
2
Maria Jose Santos-Martinez
Trinity College Dublin
Total Publications: 29
 
3
Fiona McCartney
University College Dublin
Total Publications: 7
 
4
Lidia Tajber
Trinity College Dublin
Total Publications: 83