Profile feature – Ryan Donnelly
Pharmacist and image gallery reveal how the science of the small will deliver big things.
26 October 2011
What first got you interested in science?
We had very good teachers for chemistry and physics at school, but when I came to study pharmacy at university that really stimulated my interest in science. I studied pharmacy because I felt it was a good a career more than because it was a science degree. When I studied the drug delivery and formulation aspects of the course at Queen's [University Belfast] I developed a profound interest in the scientific aspects of pharmacy.
Dr Ryan Donnelly
What was it about drug delivery that really took hold of you?
Because it was about a pharmacist's skills – we understand the physical and chemical properties of a drug substance, how the body deals with it, and how to overcome biological barriers to successful delivery. That led to working on transdermal patches for my PhD and, latterly, microneedles.
When were you first aware of microneedles?
There's that ubiquitous phrase that the best way to learn something is to have to teach it. When I was asked to give lectures on vaccine delivery in 2004, one of the things I came across was microneedles and how they could allow vaccines to be delivered across the skin in a minimally-invasive fashion. That fitted perfectly with what my research group were doing at the time with high molecular weight compounds.
What are the advantages of microneedles?
Clearly, the big advantage is that they allow us to deliver drugs across skin that we otherwise wouldn't be able to. This is because most medicines have a degree of water solubility since they have been developed for oral delivery, so that means they won't move across the skin very well because the skin is an oily barrier.
The transdermal delivery market is currently worth around USD$20Bn even with only about 20 drugs. If we could open this market up by successfully delivering water soluble molecules across the skin it would have much greater value.
There are numerous benefits for patients. Say you have a medicine that has to be administered three times a day every day of the week, if you have an elderly patient who is forgetful, treatment may not be optimum. If instead you have a microneedle patch that is only applied twice a week then you would clearly improve treatment – vastly.
If you have a medication that is rapidly metabolised by the liver, you are losing up to 60-70 per cent of the medicine, and getting formation of a range of metabolites that could have side effects. If you deliver such a drug across the skin you are straight into the systemic circulation and you could deliver a lower dose and reduce side effects.
Can you deliver all drugs this way?
Probably one of biggest considerations is that the biotechnology boom has produced a range of important peptide and protein drugs. Currently, the only way they can be given is by injection, since this avoids acid destruction by the stomach and overcomes poor gastrointestinal absorption of these large, complex, molecules. Injections are not really desirable, due to needle phobia, risk of infection and problems with disposal of needles, especially in the developing world. Even some diabetics wouldn't be completely compliant. If we could find a way to take administration of these exciting new medicines out of the hands of skilled practitioners in the hospital environment and place it in the hands of ordinary people in their own homes, we would create a profound advantage and greatly improve patient care.
With microneedles it doesn't matter what size the molecules are as long as they are water soluble, so it could be insulin, factor VIII for haemophiliacs or various hormones. Vaccine delivery is obviously a big area for development.
What are your microneedles made from?
Our group at Queen's don't make 'traditional' metal or silicon microneedles. We use novel polymers that dissolve in the skin to deliver a bolus dose [a large dose in one go like an injection] or, most interestingly, crosslinked polymeric systems that swell in skin to facilitate controlled drug administration.
Why not silicon or metal?
Historically, the reason that metal and silicon have been used in microneedles is because the manufacturing technology originated from the electronics industry – microchips are made of silicon. If a silicon microneedle broke in your skin how's it going to be metabolised? It can't. Silicon is not a biomaterial approved by any main regulators. You could never use that in a patient. With metal microneedle coated with a drug or vaccine, there's nothing to stop you sticking the microneedles into someone else after removing them from your own skin. This could lead to cross-contamination and you would need special disposal procedures too.
With our polymer system the microneedles are self-disabling. They dissolve in the skin or become soft in the skin so you could never stick them in another person, either on purpose or, more likely, by accident.
What types of microneedles do you work on?
First, a soluble system. You pop the drug into a polymer which dissolves and releases the drug in the skin.
The second example is a hydrogel system. The drug is not in the microneedles which are made from a cross-linked hydrogel matrix that's hard in the dry state. When the microneedles enter the skin, they absorb skin interstitial fluid and swell and this allows controlled administration of the drug from an attached transdermal patch. This facilitates administration of greater doses of drug, over a longer period of time. Importantly, these hydrogel microneedles are removed from skin completely intact, but are then too soft for re-insertion
You can also combine this with an electrical current for pulsatile delivery to mimic normal secretion of hormones by the body for example, or the rapid delivery of a vaccine or local anaesthetic.
You seem to use bioimaging a lot in your research… how useful is this?
Probably the most useful imaging technique we use is optical coherence tomography. Basically, it is the optical analogue of ultrasound – multiple pulses of laser light are used and the scattered and reflected radiation is collected to make an image down to about 2-3mm deep in the skin. This allows us to study how deep the microneedles have gone in, how they are swelling or dissolving and then how the skin closes again.
What funding have you received from BBSRC?
We've had two recent grants from BBSRC. Firstly, a three-year programme looking at peptide and protein delivery. The Follow-on-Funding (FoF) came after that to specifically look at safety evaluations in vitro and in vivo with view to taking the technology forward to commercialisation. Over both projects, we illustrated the capabilities of the hydrogel system to swell in the skin and deliver a wide range of therapeutically-useful drug substances.
And what are you working on now?
The success with the BBSRC funding allowed us to protect our work through an international patent application and gave us the track record to get a grant from the Wellcome Trust to pay for the imaging equipment, and then a small Royal Society grant to look at delivering gene therapy.
We also have running a three-year grant from EPSRC, in which the idea is to use microneedles in the reverse sense. If we can deliver drugs through microneedles, whatever is in the skin interstitial fluid can come out the other way. This fluid is in balance with blood, so it's a way of indirect blood sampling. This further development of the hydrogel technology would be very useful in minimally-invasive monitoring of premature neonates.
Since this means you would not have to take blood samples, the possibility exists to devise a unique roadside test for illegal drugs and prescription drugs that could affect driving performance.
All of this was made possible by the work we did during the tenure of the BBSRC grants.
Are you taking steps to commercialisation?
As a result of work done during the BBSRC FoF, we have two industrial development contracts running to develop the microneedles as a commercial product. We can't disclose the company names for obvious reasons. One application is for low molecular weight compound, and the other is for active cosmetic ingredients.
How are the commercial products developing?
The first is more blue skies thinking to show microneedles can deliver a range of active cosmetic ingredients into the skin, to demonstrate the utility of technology. The other one is pushing towards clinical trials with low molecular weight compounds. We have recently done preliminary investigational work with a number of international vaccine firms and a UK diagnostics company and initial results are promising.
It all sounds very exciting…
It's going great and to make things even better, I have been awarded the Royal Pharmaceutical Society's prestigious Science Award 2011 for my work on microneedles.
So what's behind the success?
In the School of Pharmacy at Queen's, our skill is in formulation science, rather than engineering of metals or silicon. This gives us a unique insight into novel applications of polymeric systems and their utility in microneedles research. As pharmacists, we understand how to take laboratory developments through to the end-user, the patient.
In what way?
With any sophisticated drug delivery system, if the average person in street can't use it, or doesn't like using it, or uses it in an unsafe way that harms themselves or others, then that's going to kill your technology. You need something that's safe and easy to use for every member of the public.
Are there any microneedle drug delivery products on the market now?
No, none on the market yet, because the type of safety investigations that we've been looking at aren't complete yet. Ultimately you're only going to assure regulators a new delivery technology is both safe and efficacious with extensive clinical studies.This is where interaction with industry is essential. All of the materials we use to make our microneedles are already in widespread use in other approved pharmaceutical and healthcare products, so we're confident that what we're doing will be successful.
What else is coming up in the future?
There are number of exciting new ideas that we're working on at the minute but I can't go into them, for obvious reasons!
Ah, go on…
Well, one thing to aim for is a closed loop delivery system: one set of microneedles for diagnostics to continuously monitor your blood and then a signal is sent to another microneedle array to deliver drugs accordingly. For instance, one set of microneedles to monitor blood glucose and another to deliver insulin. That's one possibility, but there are a number of things in pipeline.
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