Characterization of the Calu-3 cell line as a tool to screen pulmonary drug delivery.
The objective of this research was to examine the human sub-bronchial gland cell line, Calu-3, and assess its potential as a metabolic and transport model to study drug delivery to the respiratory epithelium. The present studies were conducted using Calu-3 cells grown in Transwells(R) or in multiwell cluster plates. TEER values for Calu-3 monolayers were determined using the World Precision Instrument Voltohmmeter and STX-2 electrode. The results confirmed that Calu-3 cells form tight monolayers and give appreciable TEER values in culture when grown under air-interface conditions. Permeability data for small lipophilic molecules across Calu-3 monolayers suggested that the cell line is a suitable model to examine the transport of low molecular weight substances and xenobiotics. Calu-3 cells were also found to efflux FITC-transferrin (MW 80000) in a polarized manner. The metabolic capacity of Calu-3 cells was also examined. The P4501A1 and P4502B isozymes were determined to be functional, but not inducible, with fluorescent resorufin assays. The data indicated that the Calu-3 cell line may be useful for studying the contributions of bronchial epithelial cells to mechanisms of drug delivery at the respiratory epithelium.
Foster
K A
KA
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, USA.
Avery
M L
ML
Yazdanian
M
M
Audus
K L
KL
D000280:Administration, Inhalation; D001189:Aryl Hydrocarbon Hydroxylases; D002478:Cells, Cultured / Q000166:cytology* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065702:Cytochrome P-450 CYP2B6; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism
D005456:Fluorescent Dyes; D007546:Isoquinolines; D003577:Cytochrome P-450 Enzyme System; C017475:lucifer yellow; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D019363:Cytochrome P-450 CYP1A1; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating