Retinoic acid and hydrocortisone strengthen the barrier function of human RPMI 2650 cells, a model for nasal epithelial permeability |
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Authors: | Levente Kürti Szilvia Veszelka Alexandra Bocsik Béla Ózsvári László G. Puskás Ágnes Kittel Piroska Szabó-Révész Mária A. Deli |
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Affiliation: | .Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, 6726 Szeged, Hungary ;.Department of Pharmaceutical Technology, University of Szeged, Eötvös u. 6, 6720 Szeged, Hungary ;.Avidin Ltd., Alsókikötő sor 11, 6726 Szeged, Hungary ;.Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony u. 43, 1083 Budapest, Hungary |
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Abstract: | The nasal pathway represents an alternative route for non-invasive systemic administration of drugs. The main advantages of nasal drug delivery are the rapid onset of action, the avoidance of the first-pass metabolism in the liver and the easy applicability. In vitro cell culture systems offer an opportunity to model biological barriers. Our aim was to develop and characterize an in vitro model based on confluent layers of the human RPMI 2650 cell line. Retinoic acid, hydrocortisone and cyclic adenosine monophosphate, which influence cell attachment, growth and differentiation have been investigated on the barrier formation and function of the nasal epithelial cell layers. Real-time cell microelectronic sensing, a novel label-free technique was used for dynamic monitoring of cell growth and barrier properties of RPMI 2650 cells. Treatments enhanced the formation of adherens and tight intercellular junctions visualized by electron microscopy, the presence and localization of junctional proteins ZO-1 and β-catenin demonstrated by fluorescent immunohistochemistry, and the barrier function of nasal epithelial cell layers. The transepithelial resistance of the RPMI 2650 cell model reached 50 to 200 Ω × cm2, the permeability coefficient for 4.4 kDa FITC-dextran was 9.3 to 17 × 10−6 cm/s, in agreement with values measured on nasal mucosa from in vivo and ex vivo experiments. Based on these results human RPMI 2650 cells seem to be a suitable nasal epithelial model to test different pharmaceutical excipients and various novel formulations, such as nanoparticles for toxicity and permeability.Electronic supplementary materialThe online version of this article (doi:10.1007/s10616-012-9493-7) contains supplementary material, which is available to authorized users. |
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Keywords: | RPMI 2650 Human nasal epithelial cell Retinoic acid Hydrocortisone Cell microelectronic sensing Paracellular permeability |
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