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Improved In Vitro Model for Intranasal Mucosal Drug Delivery: Primary Olfactory and Respiratory Epithelial Cells Compared with the Permanent Nasal Cell Line RPMI 2650

1
Institute of Applied Biotechnology, University of Applied Science Biberach, Hubertus-Liebrecht Straße 35, 88400 Biberach, Germany
2
Institute of Analytical and Bioanalytical Chemistry, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany
3
School of Life Sciences, Technical University of Munich, Liesel-Beckmann-Straße 4, 85354 Freising-Weihenstephan, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2019, 11(8), 367; https://doi.org/10.3390/pharmaceutics11080367
Received: 24 June 2019 / Revised: 18 July 2019 / Accepted: 20 July 2019 / Published: 1 August 2019
(This article belongs to the Special Issue Drug Delivery across Biological Barriers)
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Abstract

Background: The epithelial layer of the nasal mucosa is the first barrier for drug permeation during intranasal drug delivery. With increasing interest for intranasal pathways, adequate in vitro models are required. Here, porcine olfactory (OEPC) and respiratory (REPC) primary cells were characterised against the nasal tumour cell line RPMI 2650. Methods: Culture conditions for primary cells from porcine nasal mucosa were optimized and the cells characterised via light microscope, RT-PCR and immunofluorescence. Epithelial barrier function was analysed via transepithelial electrical resistance (TEER), and FITC-dextran was used as model substance for transepithelial permeation. Beating cilia necessary for mucociliary clearance were studied by immunoreactivity against acetylated tubulin. Results: OEPC and REPC barrier models differ in TEER, transepithelial permeation and MUC5AC levels. In contrast, RPMI 2650 displayed lower levels of MUC5AC, cilia markers and TEER, and higher FITC-dextran flux rates. Conclusion: To screen pharmaceutical formulations for intranasal delivery in vitro, translational mucosal models are needed. Here, a novel and comprehensive characterisation of OEPC and REPC against RPMI 2650 is presented. The established primary models display an appropriate model for nasal mucosa with secreted MUC5AC, beating cilia and a functional epithelial barrier, which is suitable for long-term evaluation of sustained release dosage forms. View Full-Text
Keywords: barrier model; nose-to-brain; primary cells; RPMI 2650; olfactory epithelium; respiratory epithelium barrier model; nose-to-brain; primary cells; RPMI 2650; olfactory epithelium; respiratory epithelium
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Ladel, S.; Schlossbauer, P.; Flamm, J.; Luksch, H.; Mizaikoff, B.; Schindowski, K. Improved In Vitro Model for Intranasal Mucosal Drug Delivery: Primary Olfactory and Respiratory Epithelial Cells Compared with the Permanent Nasal Cell Line RPMI 2650. Pharmaceutics 2019, 11, 367.

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