Transport-proteins influence the lung uptake of inhaled drugs

A study by MedUni Vienna’s Department of Clinical Pharmacology has identified two transport proteins that can influence the permeability of the lung epithelial barrier for certain drugs. Inhibiting these increases the amount of inhaled drugs that reach their target, and thus their effectiveness.

Orally inhaled drugs need to cross the epithelial cell layer which lines the airways before they can reach their pharmacological target sites in lung tissue. It is assumed that this barrier has a higher permeability to drug molecules than other biological barriers, such as the blood-brain barrier. Nevertheless, pulmonary epithelial cells abundantly express different transport-proteins, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which may theoretically restrict the permeability of the lung epithelial barrier for certain drugs. However, due to a lack of experimental methodology, the effect of transport-proteins on the lung uptake of inhaled drugs has hardly been investigated. In this project, which has been published by Severin Mairinger (Department of Clinical Pharmacology) in the top journal Journal of Controlled Release, it could be shown with PET imaging in animal models that P-gp and BCRP exert a similar effect at the lung epithelial barrier as at the blood-brain barrier. In absence of both P-gp and BCRP activity was the lung and brain uptake of a model P-gp/BCRP substrate substantially increased. This suggests that P-gp and BCRP may play an important role for the therapeutic efficacy of certain inhaled drugs. This study has been conducted under supervision of Oliver Langer (Department of Clinical Pharmacology) and received funding from the Society for Research Promotion Lower Austria [Gesellschaft für Forschungsförderung Niederösterreich].

Impact of P-gp and BCRP on pulmonary drug disposition assessed by PET imaging in rats. Severin Mairinger, Irene Hernández-Lozano, Thomas Filip, Michael Sauberer, Mathilde Löbsch, Johann Stanek, Thomas Wanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer. J Control Release 349: 109’117 (2022) doi: 10.1016/j.jconrel.2022.06.065