In this collaborative paper—our second with the Malaysian team led by Dr Choon Fu Goh—we examine some commercially available cosmetic products and ask what lessons we can learn from them to enhance pharmaceutical microneedle product translation and commercialisation.
We have known, for a long time, that the regulatory hurdles for pharmaceutical products are much greater than those for cosmetic products. Still, it’s interesting to see how cosmetic microneedle products have surged years (if not decades) ahead of their pharmaceutical counterparts, particularly in the Asian market. A low regulatory hurdle could spur innovation, but it could equally grow fad. How can one tell which it is? We examined a selection of commercially available cosmetic microneedle products to find out, and report our findings in this paper.
This has been an interesting paper to work on. I have admired Goh’s tenacity collecting microneedle patches from pharmacies on his various international trips across Asia for this study. Last year, I hosted him in Newcastle to conduct parts of the study, including some microscopy work and the optical coherence tomography (OCT) analysis on microneedle penetration in ex vivo pig skin. It’s rewarding to see those efforts pay off.
Citation: Chan HKY, Archbold L, Lau WM, Ng KW. Validating Otto: a Franz diffusion cell autosampler to automate in vitro permeation studies, Journal of Pharmaceutical Sciences, 2025:103837. https://doi.org/10.1016/j.xphs.2025.103837
We have a new paper out. This one is close to my heart because I personally spent many hands-on hours developing Otto.
Who’s Otto?
Otto is a Franz diffusion cell (FDC) autosampler robot. It replaces manual sampling and refilling of FDCs in a skin (and cornea, mucosal membrane, etc.) permeation experiment. Those who have worked with FDCs before would know how fiddly, time-consuming and labour-intensive that is. It’s a job most suited for a robot.
But Otto is about more than us trying to avoid menial labour. It’s about the quality of the science, too.
Let me rephrase that — it’s primarily about the quality of the science.
For a long time, we have noted many skin drug absorption studies that include unusually large sampling gaps of ≥16 hours, presumably because the researchers were unable to collect samples outside normal working hours. This sampling gap could allow the drug to accumulate in the FDC receptor chamber and, consequently, underestimate drug absorption due to sink condition being violated. We have faced similar logistical challenges ourselves as local rules prevent some researchers from working out of normal working hours. A FDC autosampler would solve these challenges, but we have not been able to afford any of the few commercial FDC automation systems available. When COVID-19 hit, and lab access was further restricted, we finally found the impetus and time to build the FDC autosampler we had always needed, for less than £500, and retrofitted it to our existing FDCs.
Thus, Otto was born.
Otto is a Franz diffusion cell (FDC) autosampler robot, adapted from the Creality Ender 3 Pro 3D printer. This picture depicts an automated skin permeation experiment using FDCs, in which Otto handled FDC sampling and refilling fully unattended. See the full paper for details on the number labels. Image reproduced under the CC BY 4.0 licence.
We have spent the last 2 years validating Otto’s performance. In this paper, we demonstrate that the sampling gap indeed led to violation of sink condition and underestimation of drug absorption. We further show that Otto improved data quality by avoiding the sampling gap. We have benchmarked Otto’s precision and accuracy against a trained researcher. We are pleased to report that it outperforms the researcher on both counts.
Otto is better than the commercial offerings in many ways. It is built on open-source technologies, using inexpensive consumables and 3D-printed custom parts, and is therefore fully customisable. It has a small footprint of just 50 cm × 46 cm. It can be retrofitted to generic FDCs and can collect up to 100 samples per experiment, fully unattended. The samples are collected directly into high-performance liquid chromatography (HPLC) autosampler vials, so it integrates seamlessly with downstream analysis without any further liquid handling, nor modification to the FDCs or analytical equipment.
Logistical, human resource and financial constraints continue to grip many research organisations long after COVID-19 restrictions have ended. Otto should prove itself a valuable asset in many research labs seeking to retrofit an automation solution to their existing FDCs.
The build instructions for Otto are too extensive to include in this paper, so we will be publishing them separately.
We have been working with Professor Katarina Novakovic‘s team for several years now to develop long-acting microneedle patch formulations based on our ULTRA technology. ULTRA stands for Ultra-long and Tunable Release of Actives. It is a polymeric composite material that confers exceptional sustained release properties.
Our work in this area is yet unpublished, but it has already attracted the attention of RTS (Radio Television of Serbia), which featured the ULTRA microneedle technology in a segment of the documentary series, A Guide to the Future (Vodič kroz budućnost). The full-length documentary is available on YouTube and is mostly in Serbian (Wing and I speak about the ULTRA microneedle technology in English). The segment about our ULTRA microneedle technology starts around the 17-minute mark.
Thanks to RTS and their crew for their invaluable time and efforts in creating this fantastic coverage.
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).
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.
We’re pleased to announce that a PhD studentship is now available in our laboratory and open for applications. The PhD studentship, generously funded by the EPSRC, will fund the tuition fees, living expenses (stipend) and research support (e.g. consumables) for one PhD student for 3.5 years. The student will work under the guidance of Keng, Wing and Katarina to develop a microimplant for drug delivery.
Interested candidates should apply online by following any one of the links below, which also contain full details of the studentship:
Just as we were about to wind down our lab operations for Christmas, we welcomed postdoctoral research associate, Dr Hassan Elsana, into our team this week. Hassan will be working on an EPSRC-funded project researching microneedle-mediated drug delivery in the skin.
This project is a collaboration with Dr Wing Man Lau (School of Pharmacy) and Dr Katarina Novakovic (School of Engineering). We have high hopes for this project.
Exciting times ahead, and I don’t just mean Christmas!
There are currently a couple of PhD studentships available within the pharmaceutics team at the School of Pharmacy, Newcastle University. Please click through the following links to find out more:
