Hydrogels are a popular drug delivery vehicle. You can encapsulate drugs including large biological macromolecules like proteins in them, to be released in the body. Some hydrogels use chemical crosslinking to create the hydrogel matrix – with the drug in it. Can protein drugs encapsulated this way participate in those crosslinks? What if they do? How will that affect their subsequent release?
We started asking these questions when attempting to deliver protein drugs by encapsulating them in hydrogel-forming microneedle array patches. These were important questions, and now we have the answers.
In this paper, we address these questions using bovine serum albumin as a model drug, and a genipin-chitosan hydrogel as the drug delivery vehicle. Using a combination of empirical fluorometry data and mathematical modelling, we investigate the kinetics of the interactions of the protein drug and genipin (the crosslinker).
Don’t get me wrong, we do socialise daily, but we don’t document it the way we document our experiments meticulously. So, before people start to disappear for their summer breaks, Wing had the brilliant idea of a lab photo and a meal together.
It was a shame that we couldn’t get everyone in one photo, but people deserve to take their holidays when they want them! So, we gathered up the boffins on two separate occasions and collected photographic evidence of them in full PPE (personal protective equipment, for the uninitiated), thoroughly committed to their research and enjoying it. We then headed off for a meal and a afternoon chat filled with laughter, talking mostly about ‘safe hobbies’.
We test our microneedles a lot to examine how they fail. The most common technique we use to quantify the mechanical strength of the microneedles is by applying axial compression (crushing the microneedles from the tip towards the base) on a texture analyser, and pinpointing the minimum force that results in microneedle failure. We’re fortunate that our lab is well equipped to perform these tests. We get a live video feed of what’s happening to each microneedle as it’s being compressed. We can also playback the videos and analyse them synchronously with the force-displacement data. This technique has proved invaluable in making sure our microneedles perform as they should.
Hence, when Dr Choon Fu Goh invited me (Keng) to contribute to this paper on the mechanical testing of microneedle strength, I jumped at the opportunity. This is our first paper together and I really enjoyed working on this. I hope the microneedle community finds it useful.
Bohan Zhou, who spent several weeks as a research intern in our lab last year, has rejoined us to study a PhD in microneedle biosensing. We have a very interesting project lined up. Welcome back, Bohan!
Many congratulations to Grace Young who has passed her PhD viva – without corrections, I might add. This is an incredible feat. Congratulations, Dr Young! This is very well deserved.
Grace was supervised by Dr Wing Man Lau, Professor Nick Jakubovics and myself. The title of her thesis is “Development of a novel antimicrobial and drug delivery strategy to combat biofilm”.
Our hands-free, ‘vac-and-fill’ micromoulding technique prevented air entrapment and bubble formation in viscous formulations when degassed under vacuum. Image from Smith E, et al. Int J Pharm 2024;650:123706. Licence: CC BY 4.0 Deed.
This paper reports the solution to a problem that took us several months to solve. We were trying to mould a microneedle array patch. There are basically two ways to do it: you fill the mould with the liquid formulation and either centrifuge it or degas it under vacuum. Both techniques are widely reported in the literature. They have been designed to force any air out of the microcavities in the mould, so that the formulation can enter them to form the microneedles. We didn’t have the right rotor to go with the centrifuge, so we opted for the vacuum degassing technique, fully expecting it to be a walk in the park. What a disappointment that turned out to be! We discovered that our formulation was too viscous to allow the air to escape. We ended up with a lot of air bubbles trapped in the liquid formulation.
We quickly realised that the vacuum degassing technique reported in the literature had used low polymer concentrations, which meant that their liquid formulations were not as viscous as ours. To micromould the microneedle array patch successfully from our viscous formulation, we had to remove the air first before filling the formulation into the mould. But how would one fill the mould under vacuum?
The answer: a modified syringe, a 3D-printed part, some painstaking calibration, and viola! The paper describes our solution in full, but here’s a peek of the contraption in action.
This is Emma’s first paper and our first together with Dr Katarina Novakovic‘s group. Congratulations, Emma, and thank you team for the hard work!
2023 seemingly left in a haste. Stepping into 2024, we welcomed our collaborators from The Hong Kong Polytechnic University (PolyU) to Newcastle, to conduct a joint study on microneedle formulation for drug delivery and diagnostics. Merab Naveed, Hubert Chan and Dr Thomas Lee from PolyU’s Biomedical Engineering Department spent nearly two weeks with us, running experiments and exchanging ideas with us. Newcastle University students, Begho Obale and Jakub Masloch, who completed their MPharm research projects with us, also lent their expertise to this joint study. Among other things, Begho made a dancing microneedle mould – the first ever reported. It was a most wonderful way to start the new year.
So how did our guests find it? I know Hubert enjoyed the unique learning experience – his words, not mine. I’m really pleased that we’re able to organise this research exchange programme. Thanks also go to Dr Wing Man Lau and Dr Hin Chung Lau of PolyU, the other two academic advisors on the project, for making this happen.
Begho made a magical dancing #microneedle mould – the one and only – and she didn't even know how. There wasn't anything magnetic in the aluminium foil, and the magnetic stirrer wasn't even on. On a more serious note, will the dancing mould birth happy microneedles?🤔 pic.twitter.com/Yul2cbIGc3
I was at the APS PharmSci conference in Reading. The veterans among us may remember the British Pharmaceutical Conference many, many years ago. That morphed into the APS PharmSci conference, which remains one of the major pharmaceutical science conferences to this day.
Of course I didn’t go there empty-handed. Our group presented two posters—one on a microneedle fabrication method (by Emma), the other on an impedimetric microneedle immunosensor (by Rach).
You can’t say that about many things nowadays, but the conference was both informative and enjoyable. There were many talks on 3D printing, which is a current passion of mine. It was also great to catch up with many old friends, colleagues and mentors, whom I had missed since moving away from Reading. I have only two regrets: I couldn’t attend the parallel sessions simultaneously, and I didn’t take enough photos. I did manage one tweet, and I deem that a notable achievement.
We will share the results of the research in due course. For now, suffice it to say that this has been a most fruitful research collaboration. Jasmine and Liv wrote after the visit:
This Easter break we were lucky enough to be given the opportunity to visit Hong Kong as part of our final year research project. We spent some time at the Hong Kong Polytechnic University working with some of the Biomedical Engineering students and staff, getting to know them personally and admiring the engineering work they do. Our work consisted of 3D printed moulds and 3D printed structures all relating to microneedles. But it wasn’t all work! The cultural side of the city was something we had never experienced before. From giant Buddha statues to the street food we ate in Mong Kok, it was truly amazing. We also got a chance to watch the amazing Hong Kong 7s tournament! When we touched down back in Newcastle (after a very, very long flight), we didn’t want it to be over.
No doubt, they enjoyed themselves. I’ll let the pictures do the talking:
If we could go back and do it all again, we would. If a similar opportunity arises in the future, we encourage every pharmacy student with interest to apply to work on such multi-discipline projects, it really was worth it.
Indeed, we’re going back next year with two other final-year MPharm students, so stay tuned for more updates!
I know, I don’t update this blog enough. When I do, I have too much to talk about. So, instead of a series of full-blown news articles, I’ll provide a summary of updates since my last post, with links to relevant twitter posts where available.
ULTRA technology
I have previously mentioned that we were developing a novel extended-release drug delivery platform (read it here , here and here). We call it Ultra-Long and Tunable Release of Actives (ULTRA). The patent for this technology was filed in October 2022. Meanwhile, development on the technology continues. Earlier this year, we had secured further funding from the Northern Accelerator to accelerate this effort. We are now seeking industrial partners to translate the technology to clinical applications. Interested parties please contact our Business Development Manager, Dr Tim Blackburn.
Litricity collaboration
We collaborate with Litricity, a German company specialising in liquid battery technology, in developing our microneedle biosensors. We were awarded a Wellcome Trust Translational Partnership grant to visit Litricity in Rosenheim, Germany, to perform some laboratory work. Rach and I flew out earlier this month to do just that. It’s been a really fruitful collaboration even at this early stage. We are really grateful to the Wellcome Trust and Litricity for their support.
We started a collaboration with the Polytechnic University of Hong Kong (PolyU) to develop 3D-printed microneedle patches for drug delivery and diagnostic applications. In December, Howard Chu and Dr Hin-Chung Lau from PolyU visited our labs in Newcastle to learn about our microneedle technology and perform experiments on the 3D-printed microneedles. As part of this collaboration, two undergraduate MPharm students (Jasmine and Liv) researched 3D-printed microneedles for their final year research project, working closely with the PolyU team. The project has already produced some interesting results. We are looking forward to visiting PolyU in 2023 for the second phase of the project. I am particularly pleased that we have been able to enrich the research experience for our MPharm students by providing an international, multidisciplinary and collaborative environment in which to thrive.
We have recently upgraded our texture analyser, which we rely on heavily to evaluate the mechanical properties of our microneedles. Prior to this upgrade, we already had the capability to record synchronous videos of the tests to help us pinpoint exactly when and how the microneedles reach the limit of their strength. The upgrade is a bespoke solution, designed by yours truly, that enables us to measure the strength of individual microneedles more reliably and more quickly. It uses 3D printing to create custom parts for the texture analyser to achieve this.
We have also recently acquired an optical coherence tomography (OCT) scanner, which can be used to rapidly assess gross internal structures in biological and non-biological samples. We will use this to analyse skin penetration of microneedles and other materials we use in our research.
An OCT image of my skin taken using our new OCT scanner.
Personnel changes
Daniel finished his MRes project and graduated with a distinction. Congratulations, Daniel!
Naeem has completed his experiments in our lab and returned to Pakistan to finalise the study.
It has been great working with both Daniel and Naeem. Both have now joined our list of distinguished alumni.
That’s it, folks!
We will be back in 2023. Have a lovely Christmas and happy new year!
