Within the Rocket Validis project (Development and Validation of an Intradermal Infusion Set) the aim is towards patient self-control in diabetes.

‘We work within a consortium towards one commonly shared goal,’ says Jeroen Wissink, founder of U-Needle BV, manufacturing next generation microneedle technology based on silicon micro/nanotechnology. He is passionate about rethinking diabetes care and other drug delivery routes, by using microneedles.

The consortium includes Inreda Diabetic, a leading innovative artificial pancreas manufacturer. Further, research companies specialised in human-centred clinical usability tests on diabetes are involved. ‘Only then we can realistically hope for a worldwide breakthrough in diabetes therapies,’ thus Wissink.

Clear goals are set in the Valides Rocket innovation project. First of all, the U-Needle™ infusion set concept will be tested clinically, to see if intradermal microneedles actually deliver insulin faster to the body than currently used subcutaneous infusion sets, without leakage.

Jeroen Wissink is optimistic about meeting this first, and crucial, requirement as U-Needle’s first product, ‘bella-mu’, was already approved last year. It is now taken into production for the European aesthetics market. Wissink’s companion Gert Veldhuis adds: ‘Jeroen and I are in this medical and pharma-business for over fifteen years now, using breakthrough nano/microtechnology. We know what it takes to develop disruptive products and getting them ready for market.’

1,5 mm
What makes U-Needle so special as compared to commonly used steel needles?

‘The needle is only 1,5 mm in length, and the drug delivery channel is only 0,15 mm in diameter,’ Jeroen starts of. ‘These scales are mandatory when it comes to intradermal injection. The well-perfused dermal area in the human body is only 2 mm in thickness. Here it is where we infuse our insulin and glucagon doses, as part of an automatic integrated device. Infusion needles, glucose sensors and other sensors are integrated into one single system.’

leakage
The avoidance of leakage has to be met carefully, Wissink stresses, since leaking infusion sets potentially may cause hyperglycemia or hypoglycemia. ‘Using proven silicon manufacturing technology, we are able to produce atom-sharp bevels,’ Wissink explains. ‘The channel area in which the drug is eventually delivered, is as small as one could wish for, avoiding leakage to the max. Further, the needle doesn’t wear out and can be re-used without the need for needle lubrication. Further, apart from one needle concepts, we are now strongly convinced an array of needles can provide fast acting insulin therapies. That is why we are researching multi-needle array concepts as well.’

disruptive
It shows that U-needle really is a disruptive and key-enabling technology. ‘Quite some rethinking in the field is involved,’ Veldhuis says. ‘We are lucky that our German and Dutch partners are evenly committed to the challenge in treating diabetes type 1 as we are. We are all headed towards setting a world premiere in using the Valides concept, for treating next generation diabetes patients.’

Main partner is Inreda Diabetics, located at Goor in the Dutch Province Overijssel, as founded fifteen years ago by Robin Koops. When diagnosed with type 1 diabetics 1995, he started working on an artificial pancreas system very successfully.

160 grams
Koops: ‘The most recent artificial pancreas apparatus model is expected to receive CE Quality Certification mid next year, and weighs only 160 grams. When sugar level rises, it is corrected by pumping insulin, to bring it down again. On the other hand, when levels are low, glucagon is dispensed. We test and develop this apparatus device for many years already, and it proves itself time and time again. The device has made me a free man again. I don’t worry about my sugar levels anymore. I was so bold as to do the cola test: after 23 years I ordered a cola while at the theatre. The artificial pancreas responded automatically and corrected the sugar level, almost in real-time.’

Response time
The U-Needle concept might be very promising in future bi-hormonal artificial pancreas systems. Nevertheless, some questions still exist about its use in daily life. Fixation and needle movement will be critical, to come to good dosing in combination with an artificial pancreas. The U-Needle concept has to replace subcutaneous infusion that now administers the insulin and glucagon infusion. This infusion requires the body quite some extra time to respond, up to 30 minutes.

‘We expect that intradermal infusion will bring down the time lag to 10 minutes, using one microneedle, or even lower when using multi-microneedle arrays,’ Jeroen Wissink states. ‘Then the response time will be in line with the natural time scales within the human body itself. That serves as our ultimate spot on the horizon, really meaning a world premiere in treating diabetes 1, that’s for sure.’

Münster
To bring these ultimate dreams towards reality one day in the near future, three German partners are key actors to do so. U-Needle and Inreda found ‘enthusiastic and trustworthy diabetic clinicians’ in Dr. med. Ludger Rose and Dr. med. Ralph Ziegler, both based in Münster.

Rose’s Institut für Diabetesforschung is specialized in performing clinical tests. ‘To bring about real change, we have to show our products are 100% safe and tested already,’ Wissink says. ‘Besides that, we need to perform various tests in early stages of development, for example on various glucose sensor principles. Also, we need to integrate needle and plaster concepts in innovative ways. Using the feedback from the labs directly into the design process, will help us make a well-argued design choice and that will help us to get the technology accepted much faster during market entry.’

Herein, another German partner is indispensable as well: Use-Lab GmbH in Steinfurt. Torsten Gruchmann c.s. have vast experience in performing large scale patients’ tests, in which qualitative feedback is monitored and analysed according to current methods available and widely accepted within social sciences.

Schwerpunt Praxis
In the first clinical tests, especially adults will be involved. Ralph Ziegler is a strong advocate of the novel pancreas and microneedle approach, being the leader of Schwerpunt Praxis für Kinder and Jugendmedizin. Especially children may benefit from next generation artificial pancreas systems, Wissink explains. ‘Children are less disciplined in handling the decease. Careful dosing is much more demanding for them as it is for grownups. Above that, they will have to deal with diabetes for a lifelong period of time. Making them forget about the decease most of their lifetime, would be a great achievement.’

Four requirements within Rocket
For the time being the collaborating partners focus on four clear requirements, set in the Rocket Valides program. Apart from the leakage goal (‘Fix microneedles firmly into the skin without leakage’), three other ones are formulated in catchwords:

  • Infuse necessary amounts of insulin without discomfort,
  • Minimize risk of clogging by using multi-microneedle systems
  • Longer (more than three days) in-use time with silicon infusion sets.

Wissink: ‘Ideally, an integrated multi-needle/plaster/infusion-concept lasts for a week, or even two weeks. The patients will be able to take off the artificial pancreas while showering or during sporty activities, only leaving the needle and plaster device in place.’

‘When, within this Rocket project, we are able to prove we can guarantee three days attachment, I will be over the moon already. Then the concept has proven feasible, and a new starting point for further development is firmly set. Innovations will most certainly follow from there, convincing key opinion leaders and – equally important – the younger user generation in the years to come. They are really in need of a next innovation step, making diabetes less troubling, replacing daily injections once and for all by smart silicon-based infusion technology.’