Labrasol® and Salts of Medium-chain Fatty Acids Can Be Combined in Low Concentrations to Increase the Permeability of a Macromolecule Marker Across Isolated Rat Intestinal Mucosae

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Title: Labrasol® and Salts of Medium-chain Fatty Acids Can Be Combined in Low Concentrations to Increase the Permeability of a Macromolecule Marker Across Isolated Rat Intestinal Mucosae
Authors: Heade, Joanne
Maher, Sam
Bleiel, Sinead B.
Brayden, David James
Permanent link: http://hdl.handle.net/10197/9944
Date: Jun-2018
Online since: 2019-04-15T09:29:46Z
Abstract: In addition to their solubilizing properties, excipients used in lipid-based formulations can improve intestinal permeability of macromolecules. We determined whether admixing of medium-chain fatty acid (MCFA) permeation enhancers with a lipoidal excipient (Labrasol®) could potentiate transepithelial flux of a poorly permeable macromolecule (fluorescein isothiocyanate dextran 4 kDa [FD4]) across rat intestinal mucosae mounted in Ussing chambers. Low concentrations of sodium caprate (C10), sodium undecylenate (C11:1), or sodium laurate (C12) combined with Labrasol® increased the apparent permeability coefficient (Papp) of FD4 to values typically seen with higher concentrations of MCFAs or Labrasol® alone. For example, combination of C11:1 (0.5 mg/mL) with Labrasol® (1 mg/mL) increased the Papp of FD4 by 10- and 11-fold over the respective individual agents at the same concentrations where no enhancement was evident. The increased enhancement ratios seen with the combinations were associated with some perturbation in intestinal histology and with attenuation of an epithelial functional measure, carbachol-stimulated inward short-circuit current. In conclusion, combining three MCFAs separately with Labrasol® increased the Papp of FD4 to values greater than those seen for MCFAs or Labrasol® alone. Ultimately, this may permit lower concentrations of MCFA to be used in combination with other excipients in oral formulations of poorly permeable molecules.
Funding Details: European Commission - European Regional Development Fund
Irish Research Council
Science Foundation Ireland
Type of material: Journal Article
Publisher: Elsevier
Journal: Journal of Pharmaceutical Sciences
Volume: 107
Issue: 6
Start page: 1648
End page: 1655
Copyright (published version): 2018 American Pharmacists Association
Keywords: Permeation enhancerMacromolecular drug deliveryEpithelial deliveryEpithelial permeabilityPeptide deliveryOral drug delivery
DOI: 10.1016/j.xphs.2018.02.012
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Veterinary Medicine Research Collection

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