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.