Characterising in vitro airway responses to inhaled particulates (360G-Wellcome-207199_Z_17_Z)
Few new inhaled medicines have reached the market in the past thirty years despite considerable investment into developing new drugs for the treatment of airway diseases. One of the main reasons for the attrition of candidate inhaled therapies during drug discovery is the induction of inflammatory responses observed in rat airways during in vivo studies. Currently, in vitro cell based assays are poorly predictive of in vivo airway responses, largely due to the different methods of drug exposure adopted in in vivo and in vitro studies. The majority of current in vitro cell based toxicity assays introduce the drug in suspension or solution whereas in during in vivo studies the exposure is performed as an aerosolised powder. This impacts the physico-chemical properties of the particles and how they interact with the airway epithelial cells and resident alveolar macrophages. The aim of this project is to compare the morphology, cell viability and inflammatory markers associated with airway cell exposure to inhaled medicines dosed in solution, suspension and as aerosolised particles. This will enable a better understanding of the physico-chemical properties of drug particles that influence airway toxicity, facilitating more predictive in vitro assessment of the safety of new inhaled medicines.
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