In a series of three articles, BBSRC Innovator of the Year 2013 winners reveal the secrets behind their innovations.
In this, the second, Overall Innovator winner Dr Ryan Donnelly explains how hydrogel-based microneedles might be the future of safe drug delivery, and how they could be used for non-invasive blood monitoring. In the first , Commercial Innovator winner Dr Anna Hine revealed the highs and lows of commercialising an elegant technique for building proteins from gene libraries. In the third , Social Innovator winner Peter Mertens recalls how his group helped prevent the bluetongue disease of sheep becoming endemic in the UK, saving the British economy an estimated £480M in 2008 alone.
How does it feel to be Overall Winner?
I was delighted and really surprised. Especially when you consider the level of competition involved. It was a great event in a fabulous location.
You've had a few awards for your microneedles… how does this rank?
This is the absolute pinnacle… where would you go from here? To be recognised by BBSRC in this way is fabulous for the research group, the university (Queen's University Belfast), and the School of Pharmacy because these awards are so prestigious and difficult to obtain.
Describe your innovation…
What we're working on are hydrogel-forming microneedle arrays (about 600µm high) formed on a solid support. What's unique about our microneedles is that they are made out of these hydrogel-forming polymers which are hard in dry state, so they will penetrate the outermost layer of the skin the stratum corneum. However, upon skin penetration they rapidly take up skin interstitial fluid to form many minute hydrogel plugs in the skin, and what this does is create a continuous unblockable conduit between the external environment and the dermal microcirculation.
What's it for?
There are two principal uses of this technology. The first is delivering large molecules across skin that you would be unable to deliver by that route, such as peptides, proteins; the likes of insulin or vaccines. But it can also be used for conventional small molecule drugs that have been developed for oral delivery which are too water soluble to penetrate the stratum corneum which is essentially an oily barrier.
The second main use is minimally invasive patient monitoring. Because the concentration of most drugs in skin interstitial fluid is in balance with that in blood plasma, if we can use a microneedle patch to extract interstitial fluid then we have a way of blood-free patient monitoring. This has particular applications in the monitoring of premature babies. These patients are typically on many medicines to keep them alive, due to their vulnerability. However, since each neonate is different and their organs are at an indeterminate stage of development, then it is vitally important that drug concentrations are monitored to optimise therapy and minimise side effects.
The difficulty also lies in the fact that these children are small, very fragile, with a limited volume of blood. It can be difficult to find a vein and a conventional needle can cause bruising and scarring. Also, you're basing the dose on body weight or surface area and titrating down from an adult dose, but children are not simply small adults and their organs will not be fully developed when they are premature, so new minimally methods of monitoring in this patient population is desirable.
This opens up great possibilities for enhancing patient care by providing a safe and effective way of delivering and monitoring a wide range of compounds, and greatly enhances the value of the transdermal drug delivery and patient monitoring markets, so there's considerable value for industry with this innovation.
Aren't there other microneedles on the market?
The benefit of our technology, with respect to other types of microneedles, is the fact that the microneedles are removed intact from the skin – they don't deposit polymer behind in the skin. But they are also self-disabling – even after one minute in skin they become too soft to ever be reinserted – meaning they don't need to be disposed of as contaminated sharps waste and alleviating any fears of accidental contamination or transmission of infection.
At what stage did BBSRC funding come in?
BBSRC funded the first grant that we got on the microneedle technology back in 2007. So BBSRC began funding the work in its infancy. The first thing we looked at was the delivery of protein and peptide drugs - things like insulin and vaccine antigens as well. That proved the concept and to fully characterise the system and work out its capabilities and make adjustments on a molecule-by-molecule basis. And all of the success that we've achieved to date, industrial interactions, and further funding from EPSRC and the Wellcome Trust for example, has all been as a result of that initial BBSRC grant.
What grants did you get after that?
Since that grant, we've had two major grants from BBSRC: first to look at patient safety; the second just announced within the last month was a large grant from the new Super Follow-on Fund to scale up microneedle manufacture to an industrial scale of production.
The other grants include an EPSRC three-year programme which is ongoing on minimally invasive patient monitoring, and Action Medical Research have funded a programme of work to follow on the neonatal monitoring because they're a children's charity, as well as a Wellcome Trust five-year study on microneedle behaviour in skin and skin recovery after microneedle removal. Then we have five awards from major companies looking at small molecule delivery, gene based vaccination and cosmeceutical delivery.
At what stage are you at with working with companies?
All these industrial interactions are to demonstrate the capability of the technology with molecules right up to and including animal studies. What this all hinges on, of course, is the ability to scale up manufacture of microneedles, which is why we were so delighted with BBSRC's continued support of the technology through the Super Follow-on Fund. And we're currently working with a major transdermal patch manufacturer to take forward the work on the BBSRC.
Can you name any company collaborators?
No! We have obviously signed confidentiality agreements with them all. Things have moved forward very quickly, which is down to hard work of my group and our ability to deliver the molecules that these companies are interested in. And, of course, the fact that our technology has distinct features not possessed by other microneedles.
We have one step application – the microneedles don't need to be stuck in and taken out - it's applied and that's that. And in contrast to silicon or metal microneedles, there is little likelihood of patient-to-patient contamination, as the microneedles are self-disabling; they take up interstitial fluid and become soft so you could never stick them in another person.
Over the next two years we'll be working very hard on the Super Follow-on Fund and collaborating with partners in transdermal patch manufacture to scale up. We will also continue to work with our other industrial partners. Another important matter working forward is to address regulatory concerns, so well will be interacting with regulatory groups in the UK and internationally to find out any perceived issues, but we're confident we can easily address them.
What got you into microneedles the first place?
My PhD work in the period 2000-2003 was about enhancing the delivery of photosensitive compounds for photodynamic therapies (when drugs are activated by light). Microneedles had recently come to the fore, so we decided to look at microneedle for photosensitive compounds to enhance treatment of superficial skin cancers, where drug penetration of topically-applied drugs was typically very inefficient. We quickly realised, however, that the microneedle technologies we had developed had much greater scope beyond photodynamic therapy.
Have you ever had any business training or are you learning it all as you go?
We're very well supported by Queen's Research and Enterprise Directorate, and we have a dedicated Commercial Development Manager, Dr Paschal McCloskey, who works very closely with me and my team. Importantly, my co-inventor on the microneedle technology, Professor David Woolfson, has a long track record of commercialising University research (e.g. Ametop Gel, Smith & Nephew PLC) and so he's been an ideal mentor over the last nine years.
What made you get into science in the first place?
I was always interested in science when I was at school. I studied 'A' level maths, physics and chemistry, which meant I could choose any science degree. But I was interested in pharmacy because it combined science with patient interaction. Once I started the pharmacy course at Queen's I quickly realised I liked pharmacology, how drugs work and, most importantly, pharmaceutical formulation and drug delivery.
I had decided by my second year of pharmacy that I wanted to do a PhD. My PhD subject was ideal, since it combined work on delivering photosensitising compounds with patient application of the novel dosage forms produced in a clinical trial in Belfast City Hospital. Many of the patients were treated successfully and, as a result, the patch technology developed was protected and subsequently licensed to a company called Swedish Pharma.
You were quite young to see early success…
Absolutely. As soon as I finished my PhD I was fortunate to step straight into a Lectureship. While this involved a very steep learning curve and a lot of early mistakes, it allowed me to become an independent scientist very early on and shape the direction of my research career from day one.
My experience as a practising pharmacist – I was still doing regular locum work 3 years ago – meant I had good experience interacting with patients. This will be important moving forwards with the microneedles, because no matter how good a discovery you have if it's not accepted by prescribers or patients then the technology becomes worthless. So we're currently conducting a number of online surveys with prescribers and with the general public. We've also talked with parents of premature babies and worked with children in primary schools where we carried out focus groups to talk about microneedles, so we're getting feedback from the medical and patient community too.
How do you find that kind of engagement?
I've always enjoyed that sort of thing. Some of the kids come up with some quite useful ideas. For example, children talking about microneedles being used to deliver vaccines came up with the idea of using them to monitor health without having to take a blood sample. It does surprise you at times how sharp they are. What we are getting back is that both patients and prescribers are in favour of microneedle technology, and that will be really important as we move forward with commercialisation.
The UK has perhaps the richest history of scientific innovation of any country in the world, and the Royal Society report The Scientific Century: securing our future prosperity shows that innovation and commercialisation are flourishing in Britain.
For example, from 2006-10 university spinout companies have floated on the stock market or been taken over for a combined total of £3.5Bn and employ 14,000 people in the UK. Furthermore, between 2000 and 2008, patents granted to UK universities increased by 136% and university spin outs had a turnover of £1.1Bn in 2007/08 (ref 1).
The perception that the UK is not successful when it comes to commercialising science, or as some have put it: "Britain invents; the world profits" is therefore clearly outdated, and that strategies to harness and increase innovation are working.
In addition to the benefits it brings, it is argued that present £7.5Bn science budget pays for itself many times over as technology is developed and then taxed as it is sold. The Medical Research Council estimates every pound it spends brings a 39p return each year (ref 2). Moreover, independent studies have shown that for maximum market sector productivity and impact, government innovation policy should focus on direct spending on research councils (ref 3).
Finally, the UK produces more publications and citations for the money it spends on research than any other G8 nation. Specifically, the UK produces 7.9% of the world's publications, receives 11.8% of citations, and 14.4% of citations with the highest impact, even though the UK consists of only 1% of the world's population (ref 1).