Evaluation of Sucrose Laurate as an Intestinal Permeation Enhancer for Macromolecules: Ex Vivo and In Vivo Studies
|Title:||Evaluation of Sucrose Laurate as an Intestinal Permeation Enhancer for Macromolecules: Ex Vivo and In Vivo Studies||Authors:||McCartney, Fiona; Rosa, Mónica; Brayden, 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 delivery; Oral insulin; Intestinal permeation enhancers; Sucrose laurate esters; Formulation excipients||DOI:||10.3390/pharmaceutics11110565||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Conway Institute Research Collection|
Veterinary Medicine Research Collection
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