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November 2023   |   Volume 25 No. 1

More than Skin Deep

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HKUMed scientists have invented a novel microneedle patch that treats skin infections such as acne through the minimally invasive, transdermal delivery of ultrasound-responsive antibacterial nanoparticles.

Acne affects around 80 per cent of teenagers worldwide and causes significant distress, both physical and emotional. It is usually caused by excessive lipid secretion – often during puberty – clogging hair follicles on the skin which enables Propionibacterium acnes (P. acnes) bacteria to flourish. This leads to pimples which can be multiple and may develop into a chronic skin condition, sometimes leaving permanent scarring.

The microneedle patch has been developed as a non-antibiotic approach that is delivered painlessly and not only treats bacterial infections but promotes skin repair too.

“Ultrasound-responsive antibacterial nanomaterials are introduced to the microneedle patch that responds to bacterial infections quickly and efficiently,” said Professor Kelvin Yeung Wai-kwok, leader of the research team from the Department of Orthopaedics and Traumatology in the School of Clinical Medicine. “We are treating acne without the use of drugs.”

When subjected to ultrasound stimulation, the modified nanoparticles – comprising ZnTCPP and ZnO – can produce a substantial amount of reactive oxygen species (ROS) that effectively oxidises the key cellular macromolecules of bacteria. The effects are also fast: the results showed that the killing of P. acnes bacteria mediated by ROS can reach to 99.73 per cent after 15 minutes of ultrasound stimulation. At the same time, the treatment reduces inflammatory markers, making the spread of further skin infections less likely.

Acne is sometimes treated with antibiotics, but this is controversial as they can potentially induce drug-resistant bacteria, and may be ineffectual when bacteria are drug-resistant or when they migrate to subcutaneous tissue. Also, the antibiotics have to get through the skin barrier, so efficiency can be quite low.

Trans-dermal delivery

Professor Yeung said: “Ours is non-antibiotic, trans-dermal delivery – the antibacterial nanoparticles permeate the skin using a microneedle patch engineered with ultrasound responsive metal-organic framework. We load the microneedles and, subject them to stimulation of the ultrasound then can generate a substantial amount of ROS. If we don’t trigger the ultrasound then no ROS is generated.

“Some people question if ROS might kill normal skin cells as well as affected ones, but if no ultrasound is triggered no ROS occurs – it’s stable and we can control the delivery. Therefore, biologically it is safer than other antibacterial nanoparticles, such as nano-silver.

“Furthermore, the treatment actually enhances skin healing, as it promotes different types of dermal cells to grow. The zinc ions released from the nanoparticles are left on the skin and stimulate skin tissue to heal, while the microneedles are biodegradable and will dissolve.”

The team initially developed the technology for orthopaedic purposes, to deal with bone infections.

“But when we realised how innovative and efficient it is, we decided to look beyond our own area and develop the microneedle for use in a field that would make a bigger impact on society,” said Professor Yeung.

“Some microneedle acne solutions do already exist, but they do not present any antibacterial feature. Antibiotics tend only to be available on prescription,” he added. “This new treatment would be suitable for use over-the-counter, without prescription. In addition, the specific killing mechanism of ROS, means that this design should also be effective against other skin infections induced by fungi, parasites, or viruses, such as athlete’s foot.”

Difficult next step

So far, all the testing has been on animals – mice injected with bacteria to produce acne. The research team are now ready to take the next step but is hampered by a lack of funding.

“We’re ready to go to human clinical trials, but it’s difficult to get to the next level,” said Professor Yeung. “To go to the next step of testing on humans, we need industry to take an interest and come in with funding. But we are scientists not business people, so making that leap is hard.

“Our aim is for this treatment to be widely available to those who need it. We have designed it to be highly effective and cheap to produce, and we want it to be available where it will have a real benefit. Skin infections affect many people and are prevalent around the world.”

First author of the paper, Mr Yiming Xiang, who is a PhD candidate under Professor Yeung’s supervision and has more than seven years’ experience in the field of bacterial infections, said: “As researchers, I hope that we can merge our technological advancements with the challenges we face in our daily lives, enabling technology to extend beyond the confines of academia and be accessible to every ordinary person.”

Professor Kelvin Yeung Wai-kwok (right) and his PhD student Mr Yiming Xiang (left).

Professor Kelvin Yeung Wai-kwok (right) and his PhD student Mr Yiming Xiang (left).

Our aim is for this treatment to be widely available to those who need it. We have designed it to be highly effective and cheap to produce, and we want it to be available where it will have a real benefit.

Portrait of Professor Kelvin Yeung Wai-kwok