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Feasibility of a 3D human airway epithelial model to study respiratory absorption

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Author: Reus, A.A. · Maas, W.J.M. · Jansen, H.T. · Constant, S. · Staal, Y.C.M. · Triel, J.J. van · Kuper, C.F.
Type:article
Date:2014
Source:Toxicology in vitro, 2, 28, 258-264
Identifier: 484788
doi: doi:10.1016/j.tiv.2013.10.025
Keywords: Biology · Respiratory absorption · 3D human airway model · Biomedical Innovation · Healthy Living · Life Triskelion BV · TARA - Toxicology and Risk Assessment PHS - Pharmacokinetics & Human Studies (tot 2013 daarna KFP) · EELS - Earth, Environmental and Life Sciences TNO Bedrijven

Abstract

The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investigated feasibility of a 3D human airway epithelial model to study respiratory absorption, in particular to differentiate between low and high absorption of substances. Bronchial epithelial models (MucilAir™), cultured at the air–liquid interface, were exposed to eight radiolabeled model substances via the apical epithelial surface. Absorption was evaluated by measuring radioactivity in the apical compartment, the epithelial cells and the basolateral culture medium. Antipyrine, caffeine, naproxen and propranolol were highly transported across the epithelial cell layer (>5%), whereas atenolol, mannitol, PEG-400 and insulin were limitedly transported (<5%). Results indicate that the 3D human airway epithelial model used in this study is able to differentiate between substances with low and high absorption. The intra-experimental reproducibility of the results was considered adequate based on an average coefficient of variation (CV) of 15%. The inter-experimental reproducibility of highly absorbed compounds was in a similar range (CV of 15%), but this value was considerably higher for those compounds that were limitedly absorbed. No statistical significant differences between different donors and experiments were observed. The present study provides a simple method transposable in any lab, which can be used to rank the absorption of chemicals and pharmaceuticals, and is ready for further validation with respect to reproducibility and capacity of the method to predict respiratory transport in humans.