TRIAL: Treatment of Respiratory Infections with inhaled AntimicrobiaLs
Lead Research Organisation:
University of Liverpool
Department Name: Material, Design & Manufacturing Eng
Abstract
The coronavirus disease (COVID-19) pandemic caused by the global spread of the severe acute respiratory syndrome-2 (SARS-CoV-2) virus has led to a staggering number of deaths worldwide and significantly increased burden on healthcare as nations have scrambled to find mitigation strategies. Viral infections such as SARS-CoV-2 can also predispose patients to bacterial co-infections. In fact, at least one in seven patients who have tested positive for COVID-19 have developed bacterial co-infections which have increased the severity and mortality of the disease. Since antiviral drugs have no effect on bacterial infections, these co-infections are treated with antibiotics. This surge in the use of antibiotic use during the COVID-19 pandemic has a detrimental effect in terms of driving the global growth of antibiotic resistance.
The goal of TRIAL is to design and test drug delivery vehicles tethered with antimicrobials to deliver the requisite therapeutic dose to tackle viral and bacterial infections in a controlled manner. The antimicrobials that are being developed in our laboratory have shown to have an effect on a wide range of respiratory viruses and bacterial pathogens. As we are using broad spectrum antimicrobials that are not antibiotics and we are therefore lowering the risk of developing antimicrobial resistance.
The technology being developed here is highly novel and will be revolutionary in the treatment of respiratory infections including that of COVID-19. We have brought together a group of world-class scientists, a clinician and an industrial partner with over 20 years' experience in their respective fields who will work to achieve the ambitious goals of the proposed work. The long term goal is the acceleration of bench to clinic impact followed by the commercialisation of the technology.
The goal of TRIAL is to design and test drug delivery vehicles tethered with antimicrobials to deliver the requisite therapeutic dose to tackle viral and bacterial infections in a controlled manner. The antimicrobials that are being developed in our laboratory have shown to have an effect on a wide range of respiratory viruses and bacterial pathogens. As we are using broad spectrum antimicrobials that are not antibiotics and we are therefore lowering the risk of developing antimicrobial resistance.
The technology being developed here is highly novel and will be revolutionary in the treatment of respiratory infections including that of COVID-19. We have brought together a group of world-class scientists, a clinician and an industrial partner with over 20 years' experience in their respective fields who will work to achieve the ambitious goals of the proposed work. The long term goal is the acceleration of bench to clinic impact followed by the commercialisation of the technology.
Publications
Mitsi E
(2023)
Respiratory mucosal immune memory to SARS-CoV-2 after infection and vaccination.
in Nature communications
| Description | The goal of TRIAL is to design and test drug delivery vehicles tethered with antimicrobials to deliver the requisite therapeutic dose to tackle viral and bacterial infections in a controlled manner. The antimicrobials that are being developed in our laboratory have shown to have an effect on a wide range of respiratory viruses and bacterial pathogens. We have developed gelatin nanoparticles tethered with nitric oxide that have been able to eradicate a broad spectrum of gram positive/gram negative bacteria (MRSA and Pseudomonas aeruginosa) and fungi (Candida albicans). These nanoparticles were tested for their ability to be used as an inhaled therpeutic. The nanoparticles displayed excellent aerosolisation parameters indicating that delivery would be to the lower respiratory tract where more severe infections take place. |
| Exploitation Route | The nanoplatform technology that we have developed can be used for the treatment of other biomedical infections such as skin and ocular surface, for example. Moreover these nanoplatforms can also be used to as drug delivery vehicles for other active agents. The technology developed here can also be used to validate ex vivo infection models. |
| Sectors | Healthcare Pharmaceuticals and Medical Biotechnology |
| Description | EPSRC Engineering in Net Zero UKRI Panel Member |
| Geographic Reach | National |
| Policy Influence Type | Contribution to new or improved professional practice |
| URL | https://www.ukri.org/events/epsrc-engineering-net-zero-showcase/ |
| Description | BBSRC International Partnership Award |
| Amount | £10,500 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2023 |
| End | 07/2023 |
| Description | iiCON Infection Innovation Consortium Tackling Infections Mini Sandpit |
| Amount | £1,500,000 (GBP) |
| Funding ID | EP/Z531145/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2024 |
| End | 08/2025 |
| Description | Aerogen |
| Organisation | Aerogen |
| Country | Ireland |
| Sector | Private |
| PI Contribution | We have developed antiviral material through current UKRI COVID19 Rapid Response funding. With this new collaboration we would like to develop this technology for an inhaled therapeutic application. |
| Collaborator Contribution | Aerogen are a world leading medical device company specialising in Respiratory Drug Delivery. They will be an active collaborator on this project and will provide the vibrating mesh nebuliser and carry out testing as appropriate in their state of the art facilities. |
| Impact | Grant will begin April 2022. This is a multidisciplinary consortium that includes the Antimicrobial Biomaterials Group, the Respiratory vaccines and infection immunology Group at LSTM, clinical collaboration from Aintree Hospital trust and industrial collaboration through Aerogen. |
| Start Year | 2022 |
| Description | Joint PhD Studentship with National Tsing Hua University |
| Organisation | National Tsing Hua University (Taiwan) |
| Country | Taiwan, Province of China |
| Sector | Academic/University |
| PI Contribution | The nanoparticle technology we have developed during the course of this grant has allowed us to develop a relationship with researchers at the National Tsing Hua University in Taiwan who specialise in Breast Cancer treatment. The aim of the studentship is to develop a nanoparticle carrier that can be used as a treatment for Breast Cancer. |
| Collaborator Contribution | The collaborators at the National Tsing Hua University have a novel mRNA molecule that work with but need a delivery platform. Our group has the platform technology. The studentship is currently fully funded for 2 years at Liverpool to develop the drug delivery vehicle and the 2 year in Taiwan to validate the technology in a biological model. |
| Impact | Joint fully funded studentship |
| Start Year | 2025 |
| Description | LSTM |
| Organisation | Liverpool School of Tropical Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We have developed antiviral material through current UKRI COVID19 Rapid Response funding. With this new collaboration we would like to develop this technology for an inhaled therapeutic application. |
| Collaborator Contribution | Professor Ferreira's group at LSTM have led the Oxford/Astra Zeneca Phase II/III clinical trials for the COVID vaccines and are world leading experts in the development of respiratory vaccines and infection immunology. |
| Impact | We have been able to secure a £1.3 M EPSRC grant entitled TRIAL: Treatment of Respiratory Infections with inhaled AntimicrobiaLs. The grant is a collaboration by Prof. Raechelle D'Sa and Dr. Jenny Hanson at University of Liverpool and Prof. Daniela Ferreira, Dr. Elena Mitsi and Dr. Andrea Collins at LSTM. Dr. Andrea Collins is a clinician who is also associated with Aintree Hospital NHS trust. |
| Start Year | 2022 |
| Description | Radboud University Nijmegen |
| Organisation | Radboud University Nijmegen |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | We are interested in testing our technologies in an in vivo infection model and have stared to engage with Radboud university as they have expertise in testing inhaled therapeutics in an infection model. |
| Collaborator Contribution | The team at Radboud are quite keen on developing a viral/bacterial superinfection model and they need inhaled treatments to benchmark their work. Therefore this partnership should be mutually beneficial should we secure joint funding. |
| Impact | We are currently applying for funding together. |
| Start Year | 2025 |
| Description | Designing Antimicrobial Biomaterials and Therapeutics in the Era of the Superbug-Invited Talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | he BioFutures Symposium 2023 was hosted by Northumbria University with the ambition to perform world leading research in design-led innovation through biology-centred technology and engineering. BioFutures Symposium 2023, we would like to connect educators, researchers, design practitioners, industrialists and students from biology, engineering, environmental sciences, architecture, fashion, innovation design, computer sciences and social sciences, to showcase and discuss the potential for interdisciplinary collaboration. The invited talk sparked intred in the filed and follow up conversations. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.northumbria.ac.uk/about-us/news-events/events/2023/07/biofutures-symposium-2023/ |
| Description | Pathways to Engineering |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The school of engineering hosted a Pathways to Engineering outreach day to present research and identify careers in Engineering. Between 50-60 high school students (year 11 students). We received feedback that, the topics brought new knowledge to the students, changed perspective and presented Engineering research in a new light. |
| Year(s) Of Engagement Activity | 2024 |
| Description | School visit-Dovedale Primary School |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | We went to Dovedale Primary School and carried out separate activities for the Year 6 (120 students) and Year 3 (120 students). We introduced them to the concepts of antimicrobial resistance through carefully designed age-appropriate presentations and targeted age-appropriate activities. We received feedback that both activities were well received and that the students were interested in Science as a career and engineering solutions to tackle future pandemics. |
| Year(s) Of Engagement Activity | 2023 |
| Description | The potential of nitric oxide therapies for the treatment of healthcare associated infections-Antibiotic Resistance and Mechanisms Workshop |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | The Antibiotic Resistance and Mechanisms Workshop is an annual event held every Nov/December by the British Society for Antimicrobial Chemotherapy. This workshop offered members of the UK community researching mechanisms of antimicrobial resistance the opportunity to meet, to consolidate and extend the expertise held within individual laboratories in the United Kingdom. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://bsac.org.uk/antibiotic-resistance-and-mechanisms-arm-workshop-for-researchers-2023/ |