Optical-fluorescent photo of the microneedles before loading with Zinc-based antibacterial nanoparticles. Image: Yeung et al, Science Advances

Towards drug-free acne treatment

8 August 2023

A patch that delivers nanoparticles directly to the site of acne can kill the bacteria responsible without drugs, show early tests in mice.

Acne is a widespread skin disease that affects up to 80% of teenagers and young adults globally. It’s caused by the build-ups of oils on the skin, which clog pores and create perfect conditions for the bacteria Propionibacterium acnes to grow.

Current treatments involve either topical creams and gels that exfoliate the skin, or antibiotics that kill the bacteria. However, gels come with side effects including irritated skin and sensitivity to sunlight, and over-use of antibiotics can result in resistance, meaning they are no longer effective. The bacteria are also able to form ‘biofilms’, which can resist antibiotic attack.

To tackle this problem, a research team led by Professor Kelvin Yeung from the Department of Orthopaedics and Traumatology at the University of Hong Kong invented a microneedle patch that delivers bacteria-killing power without antibiotics or harsh skin treatments. The details were published in Science Advances.

Patch tests

The system works by applying a patch studded with microneedles, each around 50 microns in diameter (similar to a human hair), to the affected area of skin. The needles puncture just enough skin to reach the pores, and when the patch is peeled off, the needles remain. Since the needles don’t need to reach the blood vessels to deliver their effect, they can be smaller than others that aim to distribute drugs within the body, making them amenable to being mounted on a patch.

The microneedles contain nanoparticles that are activated by ultrasound, releasing molecules that lead to the destruction of P. acnes bacteria. The ultrasound stimulates the nanoparticles so that they interact with water in the skin to create reactive oxygen species: forms of oxygen that can puncture the cell walls of bacteria and cause them to disintegrate.

The microneedles are made of a biodegradable polymer that dissolves naturally within a week. The nanoparticles, which are made of a cluster of zinc and zinc-oxide molecules, are then exposed more directly to the skin. This actually helps treat the acne as well, since zinc is an essential element for skin repair. As the zinc is absorbed by the skin cells, the entire system is broken down in the body, in contrast to nanoparticles that are built around other metals, such as gold, which may take longer to be expelled.

In tests in mice, the team found that use of the nanoparticle-loaded microneedles resulted in an antibacterial efficiency of 99.73% under 15 min of ultrasound irradiation, resulting in a decrease in levels of acne-related factors. The zinc ions also up-regulated DNA replication-related genes, promoting skin repair, so that the skin was well healed within a week of treatment.

Making it work

The results are extremely promising, but the challenge now is to make sure it can work in humans, and that it can be administered easily and cheaply. Yeung says the basic cost of the materials is low, so is confident it could be an accessible treatment, but there are several steps before that becomes clear.

First, they will need to test the patch in larger animals, with a physiology closer to humans. Then it will progress through small-scale human trials and finally a larger cohort of humans, in collaboration with industry partners.

Yeung expects side-effects to be minimal: while the reactive oxygen species released could also damage healthy skin cells, the microneedle targeting and ultrasound activation mean the exposure would be limited and contained. While many of the individual elements have been tested already – the microneedle material is already approved by the FDA – the safety aspect must be ‘absolute’, he says.

But the trials will also help determine what the best treatment regime would look like, such as how often it would need to be administered. As long as the microneedle lasts in the skin, the team showed the nanoparticles can be reactivated by the ultrasound, releasing a fresh round of reactive oxygen species. This mean several treatment rounds could be completed from one patch, rather than needing a new one every time, as a drug or gel would require.

Extending the applications

Yeung’s journey to the acne microneedle patch actually began in the field of orthopaedics, which is concerned with the musculoskeletal system, where he and his team have been researching antibacterial microneedle treatments for some time.

But the skin is easier to puncture with microneedles than bone, so they decided to extend the applications of their research to skin infections. “We wanted to try and make a real impact in one area,” said Yeung. “We wanted to transfer our knowledge to a large but particular cohort, to make a big impact on a common problem.”

With the system working so well in early animal trials, Yeung thinks there is great opportunity to apply it to different bacteria, which could in principle be killed in the same way. “We believe that this kind of antibacterial nanoparticle would be a good candidate for curing bacterial infections instead of using antibiotics,” he said.