Nanoengineered microneedle arrays for enhanced delivery of long-acting HIV medicines

Lead Research Organisation: Queen's University Belfast
Department Name: Sch of Pharmacy

Abstract

HIV/AIDS remains a major public health threat, with approximately 36.7 million people worldwide infected. In 2016, HIV-related diseases claimed almost 1 million lives globally, with 1.8 million people being newly infected that same year. Around 20.9 million people were accessing antiretroviral therapy in 2017, constituting ~54% of adults and ~43% of children infected with the virus. . In 2016, 42% of diagnoses happened at a late stage of infection and awareness and knowledge around HIV is dropping in the UK, emphasising the value of preventative treatments. Current methods of delivering medicines for treatment and prevention of HIV are far from optimal, necessitating multiple daily tablets or painful monthly injections.

In this project we will design and test a novel type of transdermal patch that has hundreds of tiny projections on its surface. Upon painless skin application, these "microneedles" will dissolve and leave behind microscopic particles of medicine for treatment or prevention of HIV. These particles will dissolve over weeks or months to deliver therapeutic doses of the medicine. We will use state-of-the art expertise, including high power computational models to design and predict the behaviour of the medicine particles, speeding up product design and informing laboratory experiments.

The technology developed here is unique and could potentially revolutionise prevention and treatment of HIV infection. It offers the opportunity for dramatically improved treatment, with potential benefits for both patients and the NHS. Ultimately, commercialisation of the technology will be the primary route by which UK industry, the NHS and patients will derive benefits. In order to attract potential industrial or venture-funding partners, it is vitally important to demonstrate proof of concept for this technology, which is the over-arching aim of the present proposal.

Planned Impact

Who will benefit from this research?
HIV/AIDS remains a major public health threat, with approximately 36.7 million people worldwide estimated to be infected. Several factors contribute to heterogeneity in the response to antiretroviral drugs, such as viral characteristics, immunological status and pharmacokinetic variability. Currently available formulations necessitate lifelong, daily dosing and suboptimal adherence results in low and variable exposure, exacerbating risk of failure in treatment and pre-exposure prophylaxis (PreP) The approach we propose here offers the opportunity for dramatically improved treatment and PreP. We will investigate a novel platform technology that will produce a sophisticated and distinctive minimally-invasive therapeutic system for treatment and PreP of HIV. This will benefit patients, the NHS and the UK pharmaceutical industry.

How will they benefit from this research?
In answering both fundamental and applied questions, this project will contribute to the UK knowledge base and economic development. This technology is likely to be of great interest to UK companies in the pharmaceuticals and medical devices sectors. The global market for pharmaceuticals is worth $980 billion per annum, with the global HIV drugs market set to reach $17.3 billion by 2020. Both markets are currently US-led. Due to its considerable scope for exploitation, the technology described here has the potential to make a significant and far-reaching impact in this field and place UK Research at the very forefront of developments, in accordance with the Government's Industrial Strategy.

Ultimately, commercialisation of the technology will be the primary route by which UK industry, the NHS and patients will derive benefits. In order to attract potential industrial or venture-funding partners, it is vitally important to demonstrate proof of concept, which is our over-arching aim. Considering the necessity to engage with potential marketing partners, contract negotiations and out-licensing, followed by industrial scale-up, validation of GMP manufacture and clinical trials, it is likely to be at least 5 years following completion of this project before economic and patient benefit begin to be realised.

The PDRAs and PhD student engaged on the project will have a unique opportunity to work at the interface of the pharmacological and chemical sciences and pharmaceutical engineering, to carry out research in a challenging environment and to receive both subject-specific and generic skills training. This will undoubtedly aid their personal and professional development and, in turn, their ultimate employability.

What will be done to ensure that they benefit from this research?
Allowing for IP considerations, academic publications, both journal articles and conference presentations, are likely to attract the interest of relevant industry. However, we will also make contact with the relevant UK industry players directly. The applicants have extensive experience in collaborative research with industry and the exploitation of University research. Two potential routes to market exist for this technology. The first option is out-licensing to one or more pharmaceutical/medical devices companies on a royalty basis. The second option is to form a University spin-out company with help from our universities'' technology transfer/commercialisation offices. Indeed, QUB is currently ranked 1st in the UK in the revenues of spin-out companies (survey published jointly by DTI and HEFCE), with UoL also very successful in this area.

Publications

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Donnelly RF (2024) The promise of microneedle technologies for drug delivery. in Drug delivery and translational research

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Magill E (2023) Solid implantable devices for sustained drug delivery. in Advanced drug delivery reviews

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Ramöller IK (2024) Intradermal delivery of the antiretroviral drugs cabotegravir and rilpivirine by dissolving microarray patches: Investigation of lymphatic uptake. in Journal of controlled release : official journal of the Controlled Release Society

 
Description Enhanced deposition of high-dose drugs in skin using arrays of tiny needles that painlessly, and without drawing blood, penetrate the skin. This means conventional needle-and-syringe-based injections could potentially be replaced for delivery of long-acting (once a week or once a month) medicines for treatment of diseases like HIV, but also other conditions, such as schizophrenia and infection with tuberculosis or malaria, for example. We are getting a lot of traction from industry in this space, as indicated by the number of funding awards associated with this project. Academic impact comes from the significant number of papers published from this award
Exploitation Route Long-acting delivery is a major priority for big pharma at present and microneedles such as those we are pioneering, can take the needle-and-syringe out of the equation, meaning at-home delivery of this growing group of medicines will be possible - This will be vitally-important in this new COVID age, as patients will not need to come to over-burdened healthcare organisations to get injections - they can treat themselves safely at home with patches that self-disable and so don't need specialised
Sectors Chemicals

Education

Healthcare

Pharmaceuticals and Medical Biotechnology

 
Description We have shown long-acting capability of microneedles - Drugs deposited in skin upon microneedle dissolution, if they possess the correct physicochemical properties, can form a depot and be absorbed into the bloodstream over days and weeks, allowing maintenance of therapeutic plasma levels in rats at least. This finding has led to a funded partnership with Janssen over a three year period and their engagement with our manufacturing partners LTS Lohmann. Merck Sharp & Dohme also funded a long-acting HIV drug project in our lab and we will soon publish the findings, which are very promising for their drug islatravir. We have also shown brain and lymph targeting of HIV drugs, with potential to eradicate HIV reservoirs
First Year Of Impact 2020
Sector Chemicals,Education,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Delivering 5-MeO-DMT transdermally using microneedle patches
Amount £114,229 (GBP)
Organisation Beckley PsyTech 
Sector Private
Country United Kingdom
Start 07/2022 
End 07/2023
 
Description Delivering TAF Intadermally using Dissolving Microneedles
Amount £89,674 (GBP)
Organisation Gilead Sciences, Inc. 
Sector Private
Country United States
Start 07/2019 
End 07/2020
 
Description Delivering two peptides transdermally using microneedle patches
Amount £146,584 (GBP)
Organisation Janssen Pharmaceutica NV 
Sector Private
Country Belgium
Start 06/2022 
End 09/2023
 
Description Develop a polymer usable in a microprotrusion-based device
Amount £183,283 (GBP)
Organisation Janssen Pharmaceutica NV 
Sector Private
Country Belgium
Start 08/2021 
End 08/2022
 
Description Innovative formulation and delivery solutions for children's medicines in low-resource settings.
Amount £198,731 (GBP)
Organisation University of Liverpool 
Sector Academic/University
Country United Kingdom
Start 03/2022 
End 05/2023
 
Description Optimisation of microneedle insertion and understanding the implications of repeat application as tools to support translation
Amount £1,240,247 (GBP)
Funding ID EP/V047221/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2021 
End 09/2024
 
Description Merck, Sharp & Dohme collaboration 
Organisation Merck
Department Merck Sharp and Dohme Ltd
Country United Kingdom 
Sector Private 
PI Contribution Use of our microneedles for long-acting delivery of key MSD compounds
Collaborator Contribution Support in terms of funding and technical information
Impact Enhanced delivery of the compounds, with animal studies now planned and increased support within MSD for taking microneedles to the clinic
Start Year 2020
 
Description Merck, Sharp & Dohme collaboration 
Organisation Merck
Department Merck Sharp and Dohme Ltd
Country United Kingdom 
Sector Private 
PI Contribution Use of our microneedles for long-acting delivery of key MSD compounds
Collaborator Contribution Support in terms of funding and technical information
Impact Enhanced delivery of the compounds, with animal studies now planned and increased support within MSD for taking microneedles to the clinic
Start Year 2020
 
Description Pharmather Inc collaboration 
Organisation PharmaTher
Country Canada 
Sector Private 
PI Contribution use of novel microneedle systems for controlled delivery of ketamine and betaine
Collaborator Contribution Funding and technical knowledge
Impact The work is just commencing now
Start Year 2021
 
Description Pharmacy Showcase 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact Visit by Northern Ireland school children from disadvantaged backgrounds to the university to engage with research in the pharmaceutical sciences and the pharmacy profession. A week-long course was attended by the children, all of whom have shown promise. They engage with our laboratory activities and have classes and workshops while staying on campus. If they score well on the test at the end of the week, they receive a 1-grade reduction for entry to the MPharm and BSc degrees at the School of Pharmacy. Our work features extensively in this Pathways Opportunity Programme each year.
Year(s) Of Engagement Activity 2022,2023,2024