title: Functional and cytometric examination of different human lung epithelial cell types as drug transport barriers.
abstract: 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.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju, Gyeongnam, 52828, Republic of Korea.|Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church St., Ann Arbor, MI, 48109, USA.
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Min
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 428 Church St., Ann Arbor, MI, 48109, USA.
authors.forename: Gus R
authors.initials: GR
authors.lastname: Rosania
authors.affiliation: College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
authors.forename: Chong-Kook
authors.initials: CK
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, 501 Jinju Daero, Jinju, Gyeongnam, 52828, Republic of Korea. shinmc@gnu.ac.kr.
authors.forename: Meong Cheol
authors.initials: MC
authors.lastname: Shin
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017097:Electric Impedance; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000493:pharmacokinetics; D008168:Lung / Q000166:cytology* / Q000378:metabolism*; D008954:Models, Biological; D010539:Permeability
chemical_list: D007546:Isoquinolines; C017475:lucifer yellow
keywords: Airway epithelial cell; Calu-3; Cytometric analysis; Drug transport; NHBE; Transwell