CriticalSorb promotes permeation of flux markers across isolated rat intestinal mucosae and Caco-2 monolayers

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Title: CriticalSorb promotes permeation of flux markers across isolated rat intestinal mucosae and Caco-2 monolayers
Authors: Brayden, David James
Bzik, V. A.
Lewis, A. L.
Illum, L.
Permanent link: http://hdl.handle.net/10197/4365
Date: Sep-2012
Abstract: Purpose CriticalSorb™ is a novel absorption enhancer based on Solutol® HS15, one that has been found to enhance the nasal transport. It is in clinical trials for nasal delivery of human growth hormone. The hypothesis was that permeating enhancement effects of the Solutol®HS15 component would translate to the intestine. Methods Rat colonic mucosae were mounted in Ussing chambers and Papp values of [14C]-mannitol, [14C]-antipyrine, FITC-dextran 4000 (FD-4), and TEER values were calculated in the presence of CriticalSorb™. Tissues were fixed for H & E staining. Caco-2 monolayers were grown on Transwells™ for similar experiments. Results CriticalSorb™(0.01% v/v) significantly increased the Papp of [14C]-mannitol, FD-4 [14C]-antipyrine across ileal and colonic mucosae, accompanied by a decrease in TEER. In Caco-2 monolayers, it also increased the Papp of [14C]-mannitol FD-4 and [14C]-antipyrine over 120 min. In both monolayers and tissues, it acted as a moderately effective P-glycoprotein inhibitor. There was no evidence of cytotoxicity in Caco-2 at concentrations of 0.01% for up to 24 h and histology of tissues showed intact epithelia at 120 min. Conclusions Solutol® HS15 is the key component in CriticalSorb™ that enables non-cytotoxic in vitro intestinal permeation and its mechanism of action is a combination of increased paracellular and transcellular flux.
Type of material: Journal Article
Publisher: Springer
Copyright (published version): 2012 Springer US
Keywords: Oral peptide permeationIntestinal permeation enhancersNasal permeation enhancersUssing chambersParacellular fluxes
DOI: 10.1007/s11095-012-0785-6
Language: en
Status of Item: Peer reviewed
Appears in Collections:Veterinary Medicine Research Collection

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