We use cookies on our website. Some are necessary for the operation of the website. You can also allow cookies for statistical purposes. You can adjust the data protection settings or agree to all cookies directly.
Data Protection Declaration
Imprint
Cell culture models of human nasal mucosa for in-vitro drug absorption studies (follow-up project to 1328-469)
Project
Project code: BfR-ZEBET-08-1328-508
Contract period: 01.09.2013
- 31.12.2014
Purpose of research: Basic research
The purpose of this project is further characterization of reconstructed organotypic human cell culture model of nasal mucosa as replacement for animal experiments in drug absorption studies in terms of the expression of active transport proteins.
Efflux of digoxin and CDCFDA, respectively, was increased significantly under simultaneous incubation with respective inhibitor. These results implied functional expression of Pgp as well as MRP1, 3 and 5. Activity of MRP2 and 4, respectively, was indicated by significant higher amounts of erythromycin and ADV, respectively, accumulated in absence of particular inhibitor.
Active transport of Gly-Sar in and through different models, respectively, suggested functionality of SLC15 proteins, if no inhibitor was added. All samples showed active uptake of OCT(N) substrate Di-ASP, which was decreased significantly by addition of inhibitor. For all models an active influx of BSP was detected as well; absorbed amounts of OATP substrate were reduced significantly under influence of inhibitor.
Indirect immunofluorescence staining resulted in positive signals for Pgp and MRP1 – 5 as well as for PEPT2 and organic cation and anion transporters in all models. Western Blot analysis showed respective bands with predicted molecular size and verified the expression of twelve selected ABC and SLC transporter proteins.
Publications: Dolberg, A.M. and Reichl, S. 'Expression of P-glycoprotein in excised human nasal mucosa and optimized models of RPMI 2650 cells', International Journal of Pharmaceutics 508, 22-33, 2016; http://dx.doi.org/10.1016/j.ijpharm.2016.05.010 Dolberg, A.M. and Reichl, S. 'Activity of Multidrug Resistance-Associated Proteins 1-5 (MRP1-5) in the RPMI 2650 Cell Line and Explants of Human Nasal Turbinate.' Mol. Pharmaceutics, 14, 1577-1590 (2017); DOI: 10.1021/acs.molpharmaceut.6b00838
Section overview
Subjects
- Biotechnology
Framework programme
Funding programme
Excutive institution
BfR - Centre for Documentation and Evaluation of Alternatives to Animal Experiments (BfR - ZEBET)
