TY  - THES
T1  - Establishment and characterization of an epithelial cell culture model for the respiratory tract relevant for in vitro studies of pulmonary drug absorption, targeting and development
A1  - Steimer,Anne
Y1  - 2006/08/17
N2  - The presented thesis describes the establishment of a cell culture model, which can serve as a screening tool in pharmaceutical research studying drug application to the lungs. It starts with a review, which gives an extensive overview on currently available cell culture models of the respiratory tract.
Cells were isolated from procine lung, grown as primary cultures on filter supports and identified as porcine alveolar epithelial cells (pAEpC). These cells grew to confluent monolayers with typical intercellular junctions. During the cultivation process, a change from heterogeneous morphology towards a monolayer predominated by type I and type II pneumocytes was observed. A maximal transepithelial resistance of about 2000 Ohm*cm² demonstrated the formation of a tight epithelial barrier. Permeation of marker compounds was reproducible throughout several cell preparations and the model proved successful in distinguishing between low and high permeable drugs. Based on these results quality control parameters were defined serving as threshold for the use of pAEpC monolayers in transport studies. Budesonide and triamcinilone acetonide were selected for permeation experiments, as examples for commercially available drugs, which are commonly administered to the lungs. Expression of P-glycoprotein (P-gp) was confirmed on protein level, although permeability studies revealed no polarity in transport of known P-gp substrates.
The porcine alveolar epithelial primary cell culture shares major hallmarks of the mammalian alveolar epithelium and it is easily available and scaled up for drug screening. Filter-grown monolayers of pAEpC can be used to study drug transport across such artificial alveolar epithelium and may represent a suitable in vitro model for pulmonary drug absorption and delivery.
KW  - P-Glykoprotein
KW  - Zellkultur
KW  - Arzneimittel
KW  - Absorption
KW  - Epithel
KW  - Atemwege
KW  - Wirkstofffreisetzung
KW  - Arzneimittelforschung
CY  - Saarbrücken
PB  - Universitäts- und Landesbibliothek
AD  - Postfach 151141, 66041 Saarbrücken
UR  - http://scidok.sulb.uni-saarland.de/volltexte/2006/651
ER  -