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.
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.
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
Magill E
(2023)
Solid implantable devices for sustained drug delivery.
in Advanced drug delivery reviews
Vora LK
(2023)
Long-acting microneedle formulations.
in Advanced drug delivery reviews
Tekko I
(2021)
Novel Bilayer Microarray Patch-Assisted Long-Acting Micro-Depot Cabotegravir Intradermal Delivery for HIV Pre-Exposure Prophylaxis
in Advanced Functional Materials
Donnelly RF
(2024)
The promise of microneedle technologies for drug delivery.
in Drug delivery and translational research
Moffatt K
(2021)
Exploration into the opinions of patients with HIV, healthcare professionals and the lay public of the use of microneedles in clinical practice: highlighting the translational potential for their role in HIV infection.
in Drug delivery and translational research
Rojekar S
(2021)
Etravirine-loaded dissolving microneedle arrays for long-acting delivery.
in European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
Zhang C
(2023)
Development of dissolving microneedles for intradermal delivery of the long-acting antiretroviral drug bictegravir.
in International journal of pharmaceutics
Abbate MTA
(2023)
Formulation of antiretroviral nanocrystals and development into a microneedle delivery system for potential treatment of HIV-associated neurocognitive disorder (HAND).
in International journal of pharmaceutics
Volpe-Zanutto F
(2022)
Hydrogel-forming microarray patches with cyclodextrin drug reservoirs for long-acting delivery of poorly soluble cabotegravir sodium for HIV Pre-Exposure Prophylaxis.
in Journal of controlled release : official journal of the Controlled Release Society
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
Ramöller IK
(2022)
HPLC-MS method for simultaneous quantification of the antiretroviral agents rilpivirine and cabotegravir in rat plasma and tissues.
in Journal of pharmaceutical and biomedical analysis
Paredes A
(2022)
Ring inserts as a useful strategy to prepare tip-loaded microneedles for long-acting drug delivery with application in HIV pre-exposure prophylaxis
in Materials & Design
Paredes AJ
(2022)
Systemic delivery of tenofovir alafenamide using dissolving and implantable microneedle patches.
in Materials today. Bio
Kinvig H
(2023)
Physiologically Based Pharmacokinetic Modelling of Cabotegravir Microarray Patches in Rats and Humans
in Pharmaceutics
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 |