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

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

Aerosol science has a significant impact on a broad range of disciplines, extending from inhaled drug delivery, to combustion science and its health impacts, aerosol assisted routes to materials, climate change, and the delivery of agricultural and consumer products. Estimates of the global aerosol market size suggest it will reach $84 billion/year by 2024 with products in the personal care, household, automotive, food, paints and medical sectors. Air pollution leads to an estimated 30-40,000 premature deaths each year in the UK, and aerosols transmit human and animal infections. More than 12 million people in the UK live with lung disease such as asthma, and the NHS spends ~£5 billion/year on respiratory therapies. Many of the technological, societal and health challenges central to these areas rely on core skills and knowledge of aerosol science. Despite this, an Industrial Workshop and online survey (held in preparation for this bid) highlighted the current doctoral skills gap in aerosol science in the UK. Participating industries reported that only 15% of their employees working with aerosol science at doctoral-level having received any formal training. A CDT in aerosol science, CAS, will fill this skills gap, impacting on all areas of science where core training in aerosol science is crucial.

Impact on the UK aerosol community: Aerosol scientists work across governmental policy, industrial research and innovation, and in academia. Despite the considerable overlap in training needs for researchers working in these diverse sectors, current doctoral training in aerosol science is fragmentary and ad hoc (e.g. the annual Fundamentals of Aerosol Science course delivered by the Aerosol Society). In addition, training occurs within the context of individual disciplines, reinforcing artificial subject boundaries. CAS will bring coherence to training in the core physical and engineering science of aerosols, catalysing new synergies in research, and providing a focal point for training a multidisciplinary community of researchers. Working with the Aerosol Society, we will establish a legacy by providing training resources for future researchers through an online training portal.

Impact on industry and public-sector partners: 45 organisations have indicated they will act as CAS partners with interests in respiratory therapies, public health, materials manufacturing, consumer and agricultural products, instrumentation, emissions and environment. Establishing CAS will deliver researchers with the necessary skills to ensure the UK establishes and sustains a scientific and technical lead in their sectors. Further, it will provide an ideal mechanism for delivering Continuing Professional Development for the existing workforce practitioners. The activity of CAS is aligned to the Industrial Strategy Challenge Fund (e.g. through developing new healthcare technologies and new materials) and the EPSRC Prosperity Outcomes of a productive, healthy (e.g. novel treatments for respiratory disease) and resilient (e.g. adaptations to climate change, air quality) nation, with both the skilled researchers and their science naturally translating to long-lasting impact. Additionally, rigorous training in responsible innovation and ethical standards will lead to aerosol researchers able to contribute to developing: regulatory standards for medicines; policy on air quality and climate geoengineering; and regulations on manufactured nano-materials.

Public engagement: CAS will provide a focal point for engaging the public on topics in aerosol science that affect our daily lives (consumer products, materials) through to our health (inhalation therapeutics, disease transmission and impacts of pollution) and the future of our planet (geoengineering). Supported by a rigorous doctoral level training in aerosol science, this next generation of researchers will be ideally positioned to lead debates on all of these societal and technological challenges.