Microphysiological models for the assessment of pulmonary concentration of inhaled aerosols
Lead Research Organisation:
University of Hertfordshire
Department Name: School of Life and Medical Sciences
Abstract
Inhaled aerosols are the treatment of choice for pulmonary diseases. Despite their common therapeutic use, many uncertainties regarding their pulmonary pharmacokinetic profile exist, linked to the difficulty of measuring properties in place. Knowing the region of deposition and local rate of permeation would allow elucidation of absorption processes for inhaled compounds. Given that, a new model is required. To cut costs and animal burden, in vitro assay is a straightforward solution. An emerging technology known as organ-on-chip has opened a new frontier of biorelevant investigative tools, allowing a 3D translation of organs on a microscale. The core of this proposal is to present a review of the current state-of-the-art in terms of knowledge gaps in pulmonary pharmacokinetics and provide elements for the construction of an in vitro model, to address such questions.
Planned Impact
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.
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.
Organisations
People |
ORCID iD |
| Darragh Murnane (Primary Supervisor) | |
| Caterina Fantuzzi (Student) |
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| EP/S023593/1 | 31/03/2019 | 29/09/2027 | |||
| 2446873 | Studentship | EP/S023593/1 | 01/11/2020 | 31/10/2024 | Caterina Fantuzzi |
| Description | The aim of my PhD project is to develop a technology known as lungs-on-chip, use it to test drugs, and therefore not use animals as first screening during drug development. Basically, the environment of the lungs is reproduced on a microscale, as pulmonary cells are grown onto a microfluidic chip. The chip will then be exposed to compounds used in routine therapy for respiratory problems. After a certain amount of time, drugs will be extracted from the chip, analysed, and quantified to define how quickly the compounds cross the cell barrier, elucidating absorption processes for inhaled compounds. The work done so far, aimed at establishing a bio-analytical method for the analysis of salbutamol and terbutaline, chosen as model hydrophilic compounds; the validation method is due also for fluticasone propionate and budesonide, as hydrophobic model compounds. |
| Exploitation Route | The outcomes of this funding might be taken forward by complementing it with a computational approach named physiologically based pharmacokinetics (PBPK), as well as adding more compounds currently used in respiratory medicine. A key ethical aspect is that the entry into force of these tools in drug discovery pipelines will reduce tests on animals, as well as touching the economic side by bringing considerable savings in the R&D process useful for the industry. |
| Sectors | Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| Description | Although the focus of this project is related to the study of pulmonary PK, the findings could further understand also of general metabolic pathways, with the possibility of setting up a global database with the results obtained by the different organs on a chip (e.g. liver, heart etc.). Converging knowledge acquired would help to understand, or possibly speed up discoveries. Another aspect to remark is the debate about which type of cells should be included in this powerful tool. Within this research, cell lines extracted from tumoral or transplanted tissues will be used. However, disease-specific tissues can be employed in organ-on-chip devices, COPD as an example, and here rises the ethical question: which should be the priority? Deciding on which disease and how it should be studied is a dilemma that is not easy to solve. At the current state of the art, assays elaborated through organ-on-chip are not part of the regulatory path. This leads to untouched territory in terms of policy and different institutions will be pulled together. On the one hand, academic researchers in partnership with industries, work in close collaboration to develop and improve this technology. On the other hand, institutions such as Food and Drug Administration (FDA) and European Medicines Agency (EMA), are called to define the gold standard tests to be completed. |
| Sector | Communities and Social Services/Policy,Healthcare,Government, Democracy and Justice,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic Policy & public services |