Journal of Controlled Release 87 (2003) 131–138 www.elsevier.com / locate / jconrel Drug transport and metabolism characteristics of the human airway epithelial cell line Calu-3 * Bogdan I. Florea, Maria L. Cassara, Hans E. Junginger, Gerrit Borchard Leiden / Amsterdam Center for Drug Research, Division of Pharmaceutical Technology, P .O. Box 9502, 2300 RA Leiden, The Netherlands Abstract Pulmonary drug delivery serves two purposes, namely the application of locally active compounds for treatment of diseases afflicting the lung, and the utilization of the pulmonary epithelia as absorption sites for macromolecular drugs. To elucidate the mechanisms involved in the pulmonary absorption and metabolism of compounds on a cellular level, cell culture models have shown to be, though limited, rather useful in predicting in vivo conditions. The Calu-3 cell line has been employed recently as a model for the airway epithelium in a number of drug transport and metabolism studies. The results of these studies, as well as an evaluation of the predictive potency of the model, are presented here.  2002 Elsevier Science B.V. All rights reserved. Keywords: Pulmonary absorption; Calu-3 cell line; Drug transport 1. Introduction phological features of the conducting airways include the epithelial lining, basement membrane, The lumen and submucosal tissue of the conduct- subepithelial connective tissue, smooth muscle, and ing airways represent the site of action for a large adventitia [1]. The epithelium of the conducting number of drugs, ranging from compounds of small airways varies from a pseudo-stratified columnar molecular weight (glucocorticosteroids, antibiotics) type, mainly consisting of three cell types (ciliated, to peptides and proteins (rhDNase). It also constitutes basal, and secretory cells), interconnected by tight a barrier against drug absorption through physical junctions in the proximal bronchi, to a progressively features, as well as metabolic activity and drug efflux more cuboidal, non-ciliated epithelium in the distal systems. As a consequence, the airway epithelium bronchioles. Different cellular sub-sets can be dis- represents a key membrane for study either as a drug tinguished in the airway epithelium. Ciliated cells transport barrier or as a potential site for drug (20–60 mm tall) make up about 50% of the epithelial toxicity. surface. With an average number of 250 cilia on the Trachea, bronchi and (respiratory) bronchioles apical surface, their major function is the propulsion form the conducting airways of the lungs. Mor- of mucus in the proximal direction and out of the lung (mucociliary escalator). Mucus is a mixture of mucus gland, goblet and epithelial cell secretions, *Corresponding author. Tel.: 131-71-527-4350; fax: 131-71- which are mainly produced by secretory cells. Sec- 527-4565. E-mail address: borchard@lacdr.leidenuniv.nl (G. Borchard). retory cells are mainly present in the distal airways, 0168-3659 / 02 / $ – see front matter  2002 Elsevier Science B.V. All rights reserved. doi:10.1016/S0168-3659(02)00356-5