Manufacture and applicator technologies for commercialisation of polymeric microneedle arrays
Lead Research Organisation:
Queen's University Belfast
Department Name: Sch of Pharmacy
Abstract
We have developed a novel type of transdermal patch with tiny needles on its surface that painlessly and without causing bleeding by-pass the skin's stratum corneum barrier. These needles either dissolve quickly, leaving tiny holes in the skin, which will let proteins and peptides enter the body, or swell, turning into a jelly-like material that keeps the holes open and allows continuous delivery. Our technology is unique and could potentially revolutionise delivery of medicines. Interestingly, we have also found that our swellable microneedles can extract fluid from the skin. This permits us to monitor the levels of drugs in a person's blood without actually taking blood samples, meaning that adverse events and complications arising from blood sampling could be prevented, to the benefit of patients Worldwide. In this project, we will focus on moving our microneedle production from laboratory scale to industrial scale and design and validation of a low-cost user friendly applicator.
Publications
Al-Kasasbeh R
(2020)
Evaluation of the clinical impact of repeat application of hydrogel-forming microneedle array patches.
in Drug delivery and translational research
Donnelly RF
(2017)
Vaccine delivery systems.
in Human vaccines & immunotherapeutics
Donnelly RF
(2018)
Microarray patches: potentially useful delivery systems for long-acting nanosuspensions.
in Drug discovery today
Donnelly RF
(2014)
Patient safety and beyond: what should we expect from microneedle arrays in the transdermal delivery arena?
in Therapeutic delivery
Donnelly RF
(2017)
How can microneedles overcome challenges facing transdermal drug delivery?
in Therapeutic delivery
Donnelly RF
(2014)
Hydrogel-forming microneedles increase in volume during swelling in skin, but skin barrier function recovery is unaffected.
in Journal of pharmaceutical sciences
Donnelly RF
(2014)
Hydrogel-forming microneedle arrays can be effectively inserted in skin by self-application: a pilot study centred on pharmacist intervention and a patient information leaflet.
in Pharmaceutical research
Kennedy J
(2017)
In vivo studies investigating biodistribution of nanoparticle-encapsulated rhodamine B delivered via dissolving microneedles.
in Journal of controlled release : official journal of the Controlled Release Society
Larrañeta E
(2014)
A proposed model membrane and test method for microneedle insertion studies.
in International journal of pharmaceutics
Larrañeta E
(2016)
A facile system to evaluate in vitro drug release from dissolving microneedle arrays.
in International journal of pharmaceutics
| Description | Project is now complete and went extremely well. My research has resulted in Europe's first, and currently only, GMP Manufacturing Licence for microneedle delivery systems, which is held by LTS Lohmann in Andernach, Germany. LTS are the world's largest transdermal patch manufacturer. Since 2013, I have worked closely with LTS on development, validation and scale-up of microneedle manufacture, previously a major roadblock to commercialisation. I initially transferred my methods of manufacture to LTS in 2013 as part of my BBSRC Super Follow-on Fund project. Since then, I have been engaged as a consultant, supporting transition of manufacture from laboratory to industrial scale and to ultimate approval by the German authorities. LTS are now capable of manufacturing microneedle patches up to batch sizes suitable for Phase 2 clinical trials, with the world's first commercial manufacturing line currently at the final planning stage. I have determined several critical quality attributes for microneedle systems and developed a complementary range of quality control tests. These tests are in routine use at LTS, who employ them in batch release processes. LTS have successfully completed Phase 1 clinical trials on hepatitis B vaccine and are now working with several major pharma partners on development of microneedle delivery systems for their molecules. My work with LTS has thus created, for the first time, the conditions necessary for microneedle manufacture at a commercial scale, making product launch and patient benefit a realistic aspiration within the next 5 years. Given that the first microneedle patents were filed in the 1970s and that progress to market had become badly stalled, the impact of my innovation for industry and, ultimately, patients is likely to be most significant. |
| Exploitation Route | I am currently collaborating with Teva, L'OREAL, Merck Sharp & Dohme, Johnson & Johnson, Randox, ViiV Healthcare, Janssen and Gilead on projects designed to develop my microneedle technologies for commercialisation and patient benefit. Indeed, as the transdermal drug delivery market is currently worth $32 billion, while being based on only 20 drugs, the value to industry, and by extension the University, will be significant. Delivery of vaccines without risk of cross-infection is an application of particular value. As my swelling MN efficiently imbibe skin interstitial fluid, employing them in blood-free diagnosis and patient monitoring is another important application. Sales of conventional "finger-prick" analysis devices for blood glucose alone total $2 billion per annum. Due to its much greater scope and freedom from blood-related complications, my MN technology also has the potential to make a significant and far-reaching impact in this field. My self-disabling MN will also be of tremendous value in the developing world, where at least 50% of the 1 billion childhood vaccines given annually are unsafe and around 3 million healthcare workers are injured annually with contaminated needles. While drug delivery products based on my MN technology are likely to be marketed first, the potential for impact of my MN-based sensors is also considerable. Approximately 40 million people are currently infected by HIV and 14 million are infected with Mycobacterium tuberculosis. Strict compliance with prescribed drug treatment plans is required for management of infected patients and control of spread. Conventional compliance monitoring is problematic, particularly in the developing world, where lack of resources and improper use of needles causes significant societal problems. Blood-free diagnosis/monitoring applications will also be of great value in treatment of the elderly and premature neonates. Development and transfer to a contract manufacturer of methods of manufacturer and quality control has enabled, for the first time, the possibility of microneedle products being manufactured at scale for the market, thus facilitating commercial return to the UK, through royalties for the university and sales for UK companies. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Description | I am currently collaborating with Teva, L'OREAL, Merck Sharp & Dohme, Johnson & Johnson, Randox, ViiV Healthcare, Janssen and Gilead on projects designed to develop my microneedle technologies for commercialisation and patient benefit. Indeed, as the transdermal drug delivery market is currently worth $32 billion, while being based on only 20 drugs, the value to industry, and by extension the University, will be significant. Delivery of vaccines without risk of cross-infection is an application of particular value. As my swelling MN efficiently imbibe skin interstitial fluid, employing them in blood-free diagnosis and patient monitoring is another important application. Sales of conventional "finger-prick" analysis devices for blood glucose alone total $2 billion per annum. Due to its much greater scope and freedom from blood-related complications, my MN technology also has the potential to make a significant and far-reaching impact in this field. My self-disabling MN will also be of tremendous value in the developing world, where at least 50% of the 1 billion childhood vaccines given annually are unsafe and around 3 million healthcare workers are injured annually with contaminated needles. While drug delivery products based on my MN technology are likely to be marketed first, the potential for impact of my MN-based sensors is also considerable. Approximately 40 million people are currently infected by HIV and 14 million are infected with Mycobacterium tuberculosis. Strict compliance with prescribed drug treatment plans is required for management of infected patients and control of spread. Conventional compliance monitoring is problematic, particularly in the developing world, where lack of resources and improper use of needles causes significant societal problems. Blood-free diagnosis/monitoring applications will also be of great value in treatment of the elderly and premature neonates. |
| First Year Of Impact | 2017 |
| Sector | Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal,Economic |
| Description | A transdermal microneedle delivery system for methotrexate treatment in paediatric rheumatic disease: Production and evaluation |
| Amount | £190,499 (GBP) |
| Funding ID | 20938 |
| Organisation | Versus Arthritis |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2016 |
| End | 01/2018 |
| Description | Collaborative Awards in Science |
| Amount | £907,730 (GBP) |
| Funding ID | UNS39792 |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2018 |
| End | 03/2022 |
| Description | Delivering TAF Intadermally using Dissolving Microneedles |
| Amount | £89,674 (GBP) |
| Organisation | Gilead Sciences, Inc. |
| Sector | Private |
| Country | United States |
| Start | 08/2019 |
| End | 07/2020 |
| Description | Healthcare Technologies |
| Amount | £821,430 (GBP) |
| Funding ID | EP/P034063/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 11/2017 |
| End | 10/2020 |
| Description | Microneedle sensors for detection of miRNA in skin |
| Amount | £70,077 (GBP) |
| Organisation | Johnson & Johnson |
| Sector | Private |
| Country | United States |
| Start | 01/2019 |
| End | 06/2019 |
| Description | Microneedle-mediated delivery of rilpivirine and gentamicin |
| Amount | £200,000 (GBP) |
| Organisation | Program for Appropriate Technology in Health (PATH) |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 01/2016 |
| End | 09/2016 |
| Description | Nanoengineered microneedle arrays for enhanced delivery of long-acting HIV medicines |
| Amount | £1,095,411 (GBP) |
| Funding ID | EP/S028919/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2019 |
| End | 09/2022 |
| Description | Ocular Research By Integrated Training And Learning |
| Amount | £4,200,000 (GBP) |
| Funding ID | 813440 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 09/2019 |
| End | 08/2022 |
| 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 | Industial partnerships |
| Organisation | Lohmann Therapeutic Systems |
| Country | United States |
| Sector | Private |
| PI Contribution | Collaborative working on microneedle scale-up, quality control and vaccination |
| Collaborator Contribution | Industrial expertise in these disciplines |
| Impact | Scalable methods of microneedle manufacture, novel quality control tests and successful vaccination of animal models |
| Start Year | 2012 |