Evaluation of Sucrose Laurate as an Intestinal Permeation Enhancer for Macromolecules: Ex Vivo and In Vivo Studies

Files in This Item:
File Description SizeFormat 
pharmaceutics-11-00565.pdf8.1 MBAdobe PDFDownload
Title: Evaluation of Sucrose Laurate as an Intestinal Permeation Enhancer for Macromolecules: Ex Vivo and In Vivo Studies
Authors: McCartney, FionaRosa, MónicaBrayden, David James
Permanent link: http://hdl.handle.net/10197/11312
Date: 31-Oct-2019
Online since: 2020-03-12T10:36:25Z
Abstract: Oral delivery of macromolecules requires permeation enhancers (PEs) adaptable to formulation. Sucrose laurate (SL) (D1216), a food grade surfactant, was assessed in Caco-2 monolayers, isolated rat intestinal tissue mucosae, and rat intestinal instillations. Accordingly, 1 mM SL increased the apparent permeability coefficient (Papp) of [14C]-mannitol and reduced transepithelial electrical resistance (TEER) across monolayers. It altered expression of the tight junction protein, ZO-1, increased plasma membrane potential, and decreased mitochondrial membrane potential in Caco-2 cells. The concentrations that increased flux were of the same order as those that induced cytotoxicity. In rat colonic tissue mucosae, the same patterns emerged in respect to the concentration-dependent increases in paracellular marker fluxes and TEER reductions with 5 mM being the key concentration. While the histology revealed some perturbation, ion transport capacity was retained. In rat jejunal and colonic instillations, 50 and 100 mM SL co-administered with insulin induced blood glucose reductions and achieved relative bioavailability values of 2.4% and 8.9%, respectively, on a par with the gold standard PE, sodium caprate (C10). The histology of the intestinal loops revealed little damage. In conclusion, SL is a candidate PE with high potential for emulsion-based systems. The primary action is plasma membrane perturbation, leading to tight junction openings and a predominant paracellular flux.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Type of material: Journal Article
Publisher: MDPI
Journal: Pharmaceutics
Volume: 11
Issue: 11
Copyright (published version): 2019 the Authors
Keywords: Oral peptide deliveryOral insulinIntestinal permeation enhancersSucrose laurate estersFormulation excipients
DOI: 10.3390/pharmaceutics11110565
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Veterinary Medicine Research Collection

Show full item record

Page view(s)

Last Week
Last month
checked on Apr 7, 2020


checked on Apr 7, 2020

Google ScholarTM



This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.