Functional and cytometric examination of different human lung epithelial cell types as drug transport barriers

To develop inhaled medications, various cell culture models have been used to examine the transcellular transport or cellular uptake properties of small molecules. For the reproducible high throughput screening of the inhaled drug candidates, a further verification of cell architectures as drug tran...

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Bibliographic Details
Published in:Archives of pharmacal research 2016, 39(3), , pp.359-369
Main Authors: Min, Kyoung Ah, Rosania, Gus R, Kim, Chong-Kook, Shin, Meong Cheol
Format: Article
Language:English
Subjects:
Biological Transport
cell culture
Cell Line, Tumor
Cells, Cultured
culture media
cultured cells
drugs
Electric Impedance
epithelial cells
Epithelial Cells - cytology
Epithelial Cells - metabolism
epithelium
Humans
image analysis
Isoquinolines - pharmacokinetics
Lung - cytology
Lung - metabolism
Medicine
Models, Biological
Permeability
Pharmacology/Toxicology
Pharmacy
Research Article
screening
약학
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Summary:To develop inhaled medications, various cell culture models have been used to examine the transcellular transport or cellular uptake properties of small molecules. For the reproducible high throughput screening of the inhaled drug candidates, a further verification of cell architectures as drug transport barriers can contribute to establishing appropriate in vitro cell models. In the present study, side-by-side experiments were performed to compare the structure and transport function of three lung epithelial cells (Calu-3, normal human bronchial primary cells (NHBE), and NL-20). The cells were cultured on the nucleopore membranes in the air–liquid interface (ALI) culture conditions, with cell culture medium in the basolateral side only, starting from day 1. In transport assays, paracellular transport across all three types of cells appeared to be markedly different with the NHBE or Calu-3 cells, showing low paracellular permeability and high TEER values, while the NL-20 cells showed high paracellular permeability and low TEER. Quantitative image analysis of the confocal microscope sections further confirmed that the Calu-3 cells formed intact cell monolayers in contrast to the NHBE and NL-20 cells with multilayers. Among three lung epithelial cell types, the Calu-3 cell cultures under the ALI condition showed optimal cytometric features for mimicking the biophysical characteristics of in vivo airway epithelium. Therefore, the Calu-3 cell monolayers could be used as functional cell barriers for the lung-targeted drug transport studies.
ISSN:0253-6269
1976-3786
DOI:10.1007/s12272-015-0704-6