Effects of surfactant-based permeation enhancers on mannitol permeability, histology, and electrogenic ion transport responses in excised rat colonic mucosae

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Title: Effects of surfactant-based permeation enhancers on mannitol permeability, histology, and electrogenic ion transport responses in excised rat colonic mucosae
Authors: Maher, Sam
Heade, Joanne
McCartney, Fiona
Brayden, David James
et al.
Permanent link: http://hdl.handle.net/10197/9945
Date: 25-Mar-2018
Online since: 2019-04-15T09:39:00Z
Abstract: Surfactant-based intestinal permeation enhancers (PEs) are constituents of several oral macromolecule formulations in clinical trials. This study examined the interaction of a test panel of surfactant-based-PEs with isolated rat colonic mucosae mounted in Ussing chambers in an attempt to determine if increases in transepithelial permeability can be separated from induction of mucosal perturbation. The aim was to establish assess if increases in permeability (i) intestinal permeability (the apparent permeability coefficient (Papp) of [14C]-mannitol), (ii) epithelial histology, and (iii) short-circuit current (ΔIsc) responses to a cholinomimetic (carbachol, CCh). Enhancement ratio increases for Papp values followed the order: C10 > C9 = C11:1 > a bile salt blend > sodium choleate > sucrose laurate > Labrasol® >C12E8 > C12 > Cremophor® A25 > C7 > sucrose stearate > Kolliphor® HS15 > Kolliphor® TPGS. Exposures that increased the Papp by ≥2-fold over 120 min were accompanied by histological damage in 94% of tissues, and by a decreased ΔIsc response to CCh of 83%. A degree of separation between the increased Papp of [14C]-mannitol, histological damage, and diminution of the ΔIsc response to CCh was observed at selected PE concentrations (e.g. Labrasol® at 2 mg/mL). Overall, this surfactant-based PE selection caused transcellular perturbation at similar concentrations to those that enhanced permeability.
Funding Details: European Commission - European Regional Development Fund
Irish Research Council
Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Journal: International Journal of Pharmaceutics
Volume: 539
Issue: 1-2
Start page: 11
End page: 22
Copyright (published version): 2018 Elsevier
Keywords: Ussing chamberIntestinal permeation enhancersSurfactant toxicityIntestinal epithelial damage
DOI: 10.1016/j.ijpharm.2018.01.008
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Veterinary Medicine Research Collection

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