Characterization of P-gp Expression and Function vs. Time and Passage in the Calu-3 Air-Interface Model for Drug Delivery to the Lung

Calu-3, a sub-bronchial epithelial cell line, cultured at the air-interfaced, has been shown to be a very reliable model for the in vitro investigation of inhalation drug delivery to the upper airways. It has been found to be superior with respect to morphology and function when compared to the liquid covered culture model (1, 2), but the Calu-3 air-interface model has not been fully investigated for P-glycoprotein (P-gp) expression (3, 4) a parameter that could influence predicted drug delivery in the lung. P-gp is a plasma membrane drug transporter, actively involved in `carrying a wide range of structurally and functionally unrelated drugs out of cells (5). P-gp has been shown to interact with some drugs routinely used in respiratory therapy (1). Another factor that may affect drug transport across the epithelium is the presence of mucus; which, in healthy lungs, aids mucociliary clearance of deposited particulate matter, acts as an antibacterial substance and prevents loss of excessive fluid from the airway due to evaporation (6). The aim of this investigation was to characterize mucus secretion and cell surface P-gp expression and function in the Calu-3 air-interface model