This is an extensive review which provides a comprehensive discussion covering nearly all spects pertaining to in vitro an ex vivo lung models in preclinical pulmonary research, with a focus on pulmonary drug disposition. It critically discusses the available models regarding their advantages and limitations and elaborate further which biopharmaceutical questions can and cannot be answered using the existing models. The review can, therefore, be considered a reference for anyone seeking to enter the field, and in practice select the appropriate lung cell cultures and the quantitative assays to measure and assess pulmonary drug absorption and dissolution
Oral inhalation results in pulmonary drug targeting and thereby reduces systemic side effects, making it the preferred means of drug delivery for the treatment of respiratory disorders such as asthma, chronic obstructive pulmonary disease or cystic fibrosis. In addition, the high alveolar surface area, relatively low enzymatic activity and rich blood supply of the distal airspaces offer a promising pathway to the systemic circulation. This is particularly advantageous when a rapid onset of pharmacological action is desired or when the drug is suffering from stability issues or poor biopharmaceutical performance following oral administration. Several cell and tissue-based in vitro and ex vivo models have been developed over the years, with the intention to realistically mimic pulmonary biological barriers. It is the aim of this review to critically discuss the available models regarding their advantages and limitations and to elaborate further which biopharmaceutical questions can and cannot be answered using the existing models.