Category: Publications

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Micromoulding microneedle array patches under vacuum, hands-free!

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.

Our latest paper, Vac-and-fill: A micromoulding technique for fabricating microneedle arrays with vacuum-activated, hands-free mould-filling, has been published in the International Journal of Pharmaceutics. It’s open access, so head over there to read the full-text article for free!

FREE full-text article

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!

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The back cover story

Our review article entitled ‘Microneedle-based devices for point-of-care infectious disease diagnostics’ has been published in the August 2021 issue (volume 11, issue 8) of Acta Pharmaceutica Sinica B, and features as the back cover story for that issue. The cover image, produced by yours truly, does not appear in the digital edition of the journal, so I am sharing it here for those who may otherwise not see it.

The cover story is available here.

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Review: Microneedle-based devices for point-of-care infectious disease diagnostics

We have published a review article on microneedles as a technological platform for diagnosing infectious diseases. In this review, we enumerate the infectious diseases that could potentially be diagnosed in the skin, examine the mechanisms of existing microneedle diagnostic technologies, and evaluate their applications in infectious disease diagnosis. This publication is timely given that we’re in the middle of a infectious disease pandemic.

Figure 1: Microneedles inserted into the skin may extract or detect disease markers in situ. Diagnostic tests for infectious diseases should ideally be both specific and rapid.

Any diagnostic test has to be specific to be useful (Figure 1). For a potentially deadly diseases, the more rapid the diagnosis, the better, because it buys precious time for the patient to seek early treatment, which could save lives. However, for infectious diseases that can be transmitted by close contact, it’s also desirable that the patient can administer the test themselves without too much discomfort. Many tests do better in meeting some of these criteria at the expense of other criteria. For example, I took the PCR test for COVID-19. I am sure the test itself was highly specific, but the nasal and throat swabs were uncomfortable. The diagnosis wasn’t exactly ‘rapid’ either — I got my result several days later (mainly due to limited test capacity at that time, but that has improved significantly since). Microneedle devices are painless to administer on the skin, and tests can produce real-time or near-real-time results. Not all of these studies have been on infectious diseases, of course. The technology is still nascent but the potentials are huge.

The review article is currently in press, but a pre-proof is already available for download from Acta Pharmaceutica Sinica B. There have been a number of minor corrections to this pre-proof (mainly typographical and referencing error) which will appear in the final publication, but the pre-proof should satisfy the impatient for now.

Congratulations to everyone involved in putting this publication together.

Read the review

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Review: Silica nanoparticles in transmucosal drug delivery

Graphical abstract

Our latest review in drug delivery is about silica nanoparticles, published this week in the open access journal, Pharmaceutics.

This is a collaborative paper with Professor Vitaliy Khutoryanskiy (University of Reading, UK), Dr Twana M. Ways (University of Sulaimani, Iraq), and our own Dr Wing Man Lau (Newcastle University, UK). In the paper, we examine the applications of silica nanoparticles in transmucosal drug delivery. We discuss different types of silica nanoparticles and their methods of preparation, including surface functionalisation strategies to facilitate interactions with mucosal surfaces.

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The paper is published under the very permissive Creative Commons Attribution Licence (CC BY 4.0), which allows you to freely share and adapt the work as long as the source is appropriately cited. Please cite this work as:

M. Ways TM, Ng KW, Lau WM, Khutoryanskiy VV (2020) Silica nanoparticles in transmucosal drug delivery. Pharmaceutics 12(8):751. doi: 10.3390/pharmaceutics12080751

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Perspective: The diagnostic potential of microneedles in infectious diseases

The recent COVID-19 pandemic brought the healthcare systems in many countries to their knees. One of the key problems that became evident early on was the lack of diagnostic tools that were rapid and readily accessible to the public.

Diagnostics is what we do as a research team. Naturally, we contemplated what we could do in a situation like this. The result is a perspective article published in Precision Nanomedicine, the official journal of the European Foundation for Nanomedicine.

The conclusion? Microneedle systems excel in many ways as a diagnostic tool. Various microneedle platforms have demonstrated advantages of portability, self-administrability, affordability and scalability over other diagnostic platforms. The potential is huge but the technology is still in its infancy. We need more research to turn that potential into tangible clinical benefits, but we can’t do it alone. Cross-disciplinary collaboration and stakeholder support will be needed to drive this effort forward.

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The article is published under the Creative Commons BY-NC-SA 4.0 licence, so please feel free to distribute widely, adapt and reuse for non-commercial purposes, and share any derived work, citing:

Dixon RV, Lau WM, Moghimi SM, Ng KW (2020) The diagnostic potential of microneedles in infectious diseases. Precision Nanomedicine 3(4):629–640 . https://doi.org/10.33218/001c.13658

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Collaborative paper on 3D cell culture for evaluating biomarker-capturing microneedle devices

Update: Author manuscript available

One of the challenges in developing microneedle devices to capture disease biomarkers from the skin is the lack of suitable skin specimens in which to test the devices. Donor skin specimens that carry the specific target diseases simply do not come by easily.

I first discussed this challenge with Eirini Velliou, Tao Chen and Guoping Lian in April 2016. We decided to tackle it by growing our own model of diseased skin in the lab. Experimental work started shortly after, and continued to develop following my relocation to Newcastle University in 2017. Earlier this week, we described the collaborative work in a joint publication in the journal Sensors and Actuators B: Chemical.

We took a grounds-up approach by growing melanoma skin cancer cells in a three-dimensional (3D) culture, supported structurally by a biocompatible polymer scaffold. This allowed us to simulate not only the biological microenvironment around the cells, but also the three-dimensional structure of the skin for microneedle insertion. Importantly, it was a simple and inexpensive, yet versatile, laboratory model to set up.

In pioneering the 3D cell culture model for evaluating microneedle devices against a skin cancer biomarker, we also demonstrated – for the first time – successful capture of S100B (a biomarker for melanoma skin cancer) in situ using our immunodiagnostic microneedle device.

Stella Totti, formerly a PhD student and now a postdoctoral researcher in Eirini’s research group, is the first author. I am especially pleased that hard work has paid off for Lorraine Dale, a former MSc student of mine, who contributed greatly to this work and is a co-author on this paper.

The paper is free to read until 28 July 2019 via this link: https://authors.elsevier.com/c/1ZBcy3IQMPEdJi

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A microneedle array biosensor that can detect skin burns

SEM image of microneedle array biosensor

We have developed a microneedle array biosensor that can detect skin burns. To make the biosensor, we devised a nanocomposite material from carbon nanotubes and a biocompatible polymer, poly(lactic acid). We then shaped the microneedle array from the nanocomposite material. The microneedles that formed were about 870 μm long, 250 μm wide, and electroactive. This meant that the microneedle array could be inserted into  the skin to detect certain analytes by electrochemistry. We verified this by using the microneedle array to detect vitamin C in solution. Interestingly, when we tested the microneedle array biosensor on skin burns and normal (non-burnt) skin, the skin specimens showed different electrochemical responses. This gives us the technological basis for a minimally invasive biosensing approach to detecting skin burns.

For more information, please see:

Skaria E, et al. (2019) Poly(lactic) acid/carbon nanotube composite microneedle arrays for dermal biosensing. Analytical Chemistry (epub ahead of print). doi: 10.1021/acs.analchem.8b04980

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Perspective: The future of skin biosensing and bioanalysis

I recently published a perspective article with Professor Syed Moein Moghimi in Precision Nanomedicine (the official journal of the European Foundation for Clinical Nanomedicine). In it, we offered our views and analysis on emerging techniques for sensing and analysing biomolecules in the skin, focusing on the capabilities and promises nanotechnology brings to the scene.

Read the article

The article is open access.

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In press: Nanoparticles designed to adhere to or penetrate mucosal tissue

Our paper on surface-functionalised nanoparticles and their ability to adhere to or penetrate mucous membranes has been accepted and published online. I congratulate my co-authors on this well-deserved outcome, and hereby present the paper to my readers:

MWays TM, Lau WM, Ng KW, Khutoryanskiy VV (2018) Synthesis of thiolated, PEGylated and POZylated silica nanoparticles and evaluation of their retention on rat intestinal mucosa in vitro. European Journal of Pharmaceutical Sciences 122:230-238.

The article is available for free from Elsevier until 29 August 2018. To access the free full text, please follow this link:

https://authors.elsevier.com/c/1XMgF3J1dIQyBp

In the paper, we demonstrated that nanoparticles whose surfaces were functionalised differently attained the ability to either adhere to or penetrate the mucus layer in the small intestines of the rat. We postulate that the same can be true in humans. This has important applications in oral drug delivery, where the nanoparticles can be tailored to target drug delivery to the gut differently, depending on the desired drug release profile.

The work was led by Professor Vitaliy Khutoryanskiy, of the University of Reading.