J Pharm Sci 2018 Jun 17;107(6):1648-1655. Epub 2018 Feb 17.
UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland. Electronic address:
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Int J Pharm 2018 Mar 16;539(1-2):11-22. Epub 2018 Jan 16.
UCD School of Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
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 assess the effects of PEs on (i) apparent permeability coefficient (P) of [C]-mannitol (ii) histology score and (iii) short-circuit current (ΔI) responses to a cholinomimetic (carbachol, CCh). Read More
AAPS J 2014 Sep 25;16(5):1064-76. Epub 2014 Jun 25.
School of Veterinary Medicine, Veterinary Sciences Centre and Conway Institute, University College Dublin, Room 214 Belfield, Dublin 4, Ireland,
10-undecylenic acid (UA) is an OTC antifungal therapy and a nutritional supplement. It is an unsaturated medium chain fatty acid (MCFA) derivative, so our hypothesis was that its 11-mer sodium salt, uC11, would improve intestinal permeation similar to the established enhancer, sodium caprate (C10), but without the toxicity of the parent saturated MCFA, decylenic acid (C11). MTT assay and high-content screening (HCS) confirmed a cytotoxicity ranking in Caco-2 cells: C11 > C10 = uC11. Read More
AAPS J 2017 01 13;19(1):244-253. Epub 2016 Oct 13.
School of Veterinary Medicine and Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Intestinal permeation enhancers (PEs) offer an attractive strategy to enable oral peptide administration. However, optimal presentation of peptide and PE from solid-dosage forms is offset by slow dissolution rates in the small intestine, which reduces the likelihood that the PE can reach the threshold concentration for sufficient permeability enhancement. The purpose of this study was to design a PE-based liquid dispersion that can improve intestinal permeation of macromolecules across Caco-2 monolayers and isolated rat/human intestinal mucosae mounted in Ussing chambers. Read More
Eur J Pharm Sci 2009 Nov 6;38(4):291-300. Epub 2009 Sep 6.
UCD School of Agriculture, Food Science and Veterinary Medicine and UCD Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
The effects of two absorption promoters, (sodium caprate (C(10)) and melittin), on intestinal permeability and viability were measured in intact rat and human colonic epithelia mounted in Ussing chambers. Apical-side addition of C(10) (10 mM) and melittin (10-50 microM) rapidly reduced the transepithelial electrical resistance (TEER) and increased the apparent permeability coefficient (Papp) of [(14)C]-mannitol and FITC-dextran-4 kDa (FD4) across colonic mucosae from both species. Effects of C(10) on flux were greater than those of melittin at the concentrations selected. Read More