The respiratory tract provides a gateway to the body for both the intentional and inadvertent delivery of drugs and other substances. Intentional drug delivery includes the delivery of drugs intended for their local effect in, for instance, the treatment of asthma and COPD. Unintentional delivery can include the inhalation of consumer products such as perfumes, household and pharmaceutical sprays. For drug delivery to the lungs, once deposition has occurred, the efficacy of the drug will depend on a number of factors. In the upper airway the deposited particles must avoid removal by mucociliary clearance, solid particles must (usually) dissolve in the fluid lining the epithelium and drug molecules must (usually) be able to cross the barriers provided by mucus and the epithelium. When considering the respiratory region of the lung (alveoli), particles must survive clearance by alveolar macrophages, be able to cross the barrier provided by the alveolar surfactant and also cross the epithelial cells. Cell-based models are valuable tools in studying how these barriers affect drug efficacy and the recent developments in such models are reviewed with a focus on the use of three dimensional (3D) models to study the effect of mucus on drug absorption.
We have further developed and validated a 3D model of SPOC1 rat tracheal cells as a potential secretagogue-free model to predict the effect of mucus hyper-secretion on drug absorption in the lung.