Aerosolised lung surfactant-based formulation stabilisation to optimise inhalable controlled drug delivery

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Exogenous lung surfactant (LS) therapies in premature babies and adults involve intratracheal instillation (ITI) of animal-derived LS dense lipoprotein formulations. Most patients in need of LS therapy are intubated, which led to the preference for an aerosolised inhalable formulation. Current clinical trials are exploring LS therapy in form of ITI and also as nebulisers in COVID19 patients to treat the acute respiratory distress syndrome, inflammatory storm and facilitate breathing. These formulations, reaching deep into the gas-exchange units (alveoli), are in their infancy despite its enormous potential, not only to be used as lung surfactant exogenous therapy, but also as inhalable drug carriers. A major hindrance is to design a nebulised formulation that will retain the physical and chemical characteristics of LS to reach and deliver drugs and is stable when reaching the alveoli. This project aims at developing new stable formulations based in the LS properties to reach deep into the lungs to optimise drug delivery. This project will require method development in form of optimisation of an organ on a chip platform to be integrated into an optical fluorescence microscope. The organ on a chip platform will be an implementation to the current ones we have working in the lab. We will implement the chip to mimic different exposure regimes in frequency, and duration, by changing different sinusoidal or quadratic flows applying various pressures. Our expected outcome is that, by the end of the project, we will have determined how to better design and stabilise the different LS-based aerosolised formulations, we will have learnt how these formulations are internalised at the alveolar epithelium, and will have characterised the metabolic, and immune responses of the alveolar epithelial cells, so we can better design future formulations. EPSRC areas: particle technology and biophysics