In vitro cell culture models for the assessment of pulmonary drug disposition

Abstract

Background: Aerosol administration of therapeutics to the respiratory system represents a significant opportunity for many classes of drugs, both small molecules and macromolecules, including recently engineered peptide and protein therapeutics. However, minimally invasive assessment of drug absorption mechanisms in vivo or from the isolated organ is prevented by the complex architecture of the lung. Thus, cell culture models of the bronchial and alveolar epithelial barriers have been developed for absorption mechanisms studies and are now widely used as in vitro screening tools. Objectives: The aim of this article is to provide an update of the published work on various in vitro models of respiratory epithelium while emphasising the advantages and limitations of each model. Methods: This review summarises recent advances in the development and characterisation of in vitro cell culture models for drug disposition studies. Conclusions: A variety of cell culture systems for modelling the respiratory epithelium have been developed and are available to the scientific community. However, to allow their full exploitation in biopharmaceutical research, the currently available models have to be further characterised, particularly regarding their expression of transporter molecules and their metabolic capabilities.

Keywords::

• alveolar epithelium
• bronchial epithelium
• drug transporters
• pulmonary drug disposition
• tight junctions

Acknowledgements

Lenka Horálková is in part funded by a personal GALENOS Marie-Curie Early Stage Research Training Fellowship (MEST CT-2004-504992).

Notes