University of Nottingham scientists and colleagues from AstraZeneca have pioneered 3D inkjet printing technology that could lead to ‘printed’ drugs exactly tailored to individual patients’ needs. But the significance of this breakthrough lies as much with the EPSRC initiatives that inspired and nurtured it as the research itself.
Words: Mark Mallett
The story revolves around the EPSRC Doctoral Training Centre in Targeted Therapeutics at Nottingham, set up in 2006 as a joint venture with pharmaceutical giant AstraZeneca.
Professor Cameron Alexander, who joined Nottingham’s School of Pharmacy in 2005, has been running the centre, and its latest 2012 incarnation, since its launch. He says the timing couldn’t have been better: “Cohort-based training – bringing PhD students together in one centre, focused on a specific area of research – was relatively new at the time. What made it doubly exciting for me was the partnership with AstraZeneca – the first of its kind. We were pioneering a new kind of training initiative, with strong commercial focus."
“It was the perfect opportunity to introduce new ways of thinking. I was particularly keen to bring in ideas inspired by a new EPSRC problem-solving initiative, the IDEAS Factory, particularly its ‘sandpit’ process. I had attended one of the very first sandpits, in 2004, which was a revelation.”
The sandpit is an intensive problem-solving workshop, tackling specific and hypothetical research challenges. The emphasis is on thinking the unthinkable; not just outside the sandpit, but way beyond the playground. Through expert moderation and with real-time peer review, the very best ideas become funded research projects, usually with a high risk element.
Professor Alexander says: “What makes a sandpit so special is the process itself: no egos, no pulling rank, all preconceptions left at the door. Positive collective energy, focused on getting results."
“In fact, the influence of the EPSRC sandpit was so strong we devised our very own sandpit process for the Doctoral Training Centre.”
True to its founding spirit, the centre’s first sandpit had a suitably speculative theme: ‘What would pharmaceuticals look like in 2050?’ From the opening speed dating-style session to the final day’s conclusions, the process was very different from what many participants had experienced before. The results, however, speak for themselves. For example, the 3D inkjet drug printing project emerged almost fully formed after the very first session.
The inkjet printing project was co-led by scientists from Nottingham and AstraZeneca, including Professor Clive Roberts and AstraZeneca’s Dr Paul Gellert. Other CDT projects included academics from a range of departments at the university as well as a total of 25 full-time PhD students – in every sense a multidisciplinary undertaking.
Despite the CDT’s focus on developing pharmaceuticals for a world 50 years into the future, the subjects it addressed, such s the UK’s ageing population and patients’ ncreasing reliance on multi-combinations of medicines were very much focussed on the here and now, and had a solid, pragmatic base.
Professor Roberts says: “We wanted to idetify novel manufacturing methods capable of producing individualised medicines tailored to a patient’s needs and, if possible, simple enough to be done at the point of care or even at home".
“Inkjet printing seemed to fit the bill, as it had already shown potential in other areas such as printed electronics and bespoke 3D printing of objects.”
"The EPSRC Centre for Doctoral Training provided me with a unique atmosphere in which to flourish. I gained vast experience in working collaboratively, actively creating interdisciplinary partnerships to gain expertise and achieve better results. Essential skills I obtained include quick and effective decision making, to enable project completion in limited time, and the ability to adapt to both academic and industrial settings with ease and diversity. The centre also provided me with experience in working successfully within areas outside of my discipline."
Dr Helen Angell, Postdoctoral Research Fellow,
Cordeliers Research Center, Paris, France
After early teething problems – which were hardly surprising, as the project was the first academic/industrial partnership of its kind – the team got into their stride, and the results began to
come together.
The printer itself used a piezo-electric inkjet head, similar to the kind found on desktop paper printers.
Ultimately, the team succeeded in devising a way to ‘print’ micron-sized dried polymer droplets containing the drug felodipine onto a water-resistant material, and then more complex formulations with two drugs and a controlled release layer. To confirm the accuracy and consistency of the microspot formulations, the team used ultrahigh- power atomic force microscopes and confocal Raman spectroscopy, a relatively new technique that allows chemical imaging without specific sample preparation. Everything checked out.
As inkjet printing is an inherently scalable technology – something with the potential to go from lab desk to commercial reality – the team had been able to prove in principle the viability of their research, although they acknowledge it is a long way from practical application. If successful, however, the consequences could be far-reaching.
The team suggest that the ‘formulation printer’ of the future could use cartridges supplied by the pharmaceutical industry to print out the patient’s specific dosage – mixing and matching the drug combinations with accuracy to the nearest nano-drop as the inkjet printer builds the prescription layer-by-layer. The EPSRC Centre for Doctoral Training provided me with a unique atmosphere in which to flourish. I gained vast experience in working collaboratively, actively creating interdisciplinary partnerships to gain expertise and achieve better results. Essential skills I obtained include quick and effective decision making, to enable project completion in limited time, and the ability to adapt to both academic and industrial settings with ease and diversity. The centre also provided me with experience in working successfully within areas outside of my discipline.
The printer could be linked via the internet to the appropriate healthcare provider, as well as to the patient’s medical records, enabling individualised dosages to be printed, monitored, and modified remotely. Naturally, each dosage would use controlled-release technology, so that it would hit the spot in the right amount at the right time. Controlled release (targeted therapeutics) is, after all, one of the reasons why the Nottingham EPSRC Centre for Doctoral Training was set
up in the first place.
Cameron Alexander (pictured above) says: "One can see how this kind of targeted therapy technology might appeal to the major companies, especially as it marks a move away from large-scale, high-cost drug manufacture."
“Academic pharmaceutical research in the UK can rarely compete with the big US groups on money. But what we can beat them on is ideas like this."
“At Nottingham we have bright, inventive students and a group of academics who want to work across divisions and who are willing to take on risky projects. This, I think, gives us an edge, and is helping us develop independent, creative leaders who enjoy working in teams.”
Andrew Megarry, a PhD student at the centre, says: “As a new researcher, having a
built-in network of people working in related areas was invaluable."
“The interdisciplinary nature of the CDT training projects provided hands-on experience with techniques from a range of disciplines. This experience proved to be incredibly useful and allowed me to make a more informed choice of PhD topic.”
Cameron Alexander says: “We’ve been able to create a model that works for everyone,
giving us the freedom to work on longterm projects, as well as the mechanism to exploit these opportunities".
“In the past, a university department would revolve around the ‘Big Professor’, attended by their subordinates. That whole approach has changed – thanks, in part, to initiatives introduced by EPSRC. It’s now more about bringing people together collaboratively; working on large-scale ventures that aren’t driven just by one big name."
“Leadership, lateral thinking and entrepreneurship are built into the training. This can be challenging, as our CDT students have got good ideas, and they know it – many of them are very entrepreneurial.
To be honest, this approach isn’t always easy to manage as a student will start
off doing one project but, as their group progresses, they might go off in directions
we don’t want them to go in; so it’s far removed from the traditional single-project
PhD. But it’s challenges like this that keep us on our toes and constantly open to
new ideas. So the process is not only developing the leadership potential of a new generation, it’s enhancing the leadership skills of senior team members."
“It’s a different way of defining leadership from what we might have done in the past, and all the better for it. The whole is greater than the sum of its parts.”
EPSRC Leadership Fellowships – a professor’s experience
EPSRC Fellowships are a direct investment in Britain’s most talented individuals to help them develop ground-breaking ideas across a range of fields.
Cameron Alexander was awarded an EPSRC Leadership Fellowship in personalised medicine in 2011.
Cameron says: “My fellowship involves some pretty radical research, in areas including synthetic biology, which I’m working on with scientists I first met at one of the first EPSRC sandpits in 2004. In fact, our research collaboration is based on ideas we first came up with then."
“I try to balance my ‘blue-skies’ work with the pragmatic research we’re doing at
the EPSRC Centre for Doctoral Training in Targeted Therapeutics at Nottingham."
“So, although my work, by its nature, goes from applied research to completely blue skies thinking, my ethos for each of these projects is that they draw from each other.”
Posted on Tuesday 15th January 2013