Suitability and functional characterization of two Calu-3 cell models for prediction of drug permeability across the airway epithelial barrier

• Published in: International journal of pharmaceutics Vol. 585; p. 119484
• Main Authors: Sibinovska, Nadica, Žakelj, Simon, Roškar, Robert, Kristan, Katja
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.07.2020
• Subjects: Air-liquid interface; Airway epithelial model; ATP-Binding Cassette Transporters - metabolism; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - metabolism; Calu-3; Cell Line; Cell Membrane Permeability - drug effects; Cell Membrane Permeability - physiology; Drug permeability; Forecasting; Humans; Liquid-liquid interface; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - metabolism; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; Vasodilator Agents - administration & dosage; Vasodilator Agents - metabolism; Airway epithelial model; Liquid-liquid interface; Air-liquid interface; Calu-3; Drug permeability
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119484

[Display omitted] The Calu-3 cell line has been largely investigated as a physiological and pharmacological model of the airway epithelial barrier. Its suitability for prediction of drug permeability across the airway epithelia, however, has not been yet evaluated by using large enough set of model drugs. We evaluated two Calu-3 cell models (air-liquid and liquid-liquid) for drug permeability prediction based on the recent regulatory guidelines on showing suitability of in vitro permeability methods for drug permeability classification. Bidirectional permeability assays using 22 model drugs and several zero permeability markers, as well as using ABC transporter substrates were conducted. Functional activity of P-gp, but not of BCRP was revealed. The potential of the Calu-3 cells to be used as a model of the nasal epithelial barrier, despite their different anatomical origin, has been demonstrated by the obtained excellent correlation with the fully differentiated 3D human nasal epithelial model (MucilAir™) for 11 model drugs, as well as by the good correlation obtained with the human nasal epithelial cell line RPMI 2650. In addition, the permeability values determined in the two Calu-3 models correlated well with the intestinal permeability model Caco-2.