Patch things up

Instead of being jabbed with a syringe to receive your medicine, what if you could pop a patch on your skin? It would deliver the drug through microneedles, which are long enough to get through the skin’s outer layer but short enough to avoid upsetting your nerve endings – so you’d barely feel it.

Now imagine that you had a chronic condition and needed to have injections regularly, perhaps even daily. What if the patch contained multiple doses of your medication, and you could control when each was released via an app on your phone? No such device currently exists on the market.

But it’s a vision that researchers at the University of North Carolina at Chapel Hill are working to realise. Led by Juan Song, professor of pharmacology and Wubin Bai, assistant professor of applied physical sciences, the team have developed a new delivery system that allows drug release from individual microneedles to be scheduled and triggered via a smartphone or computer.

Dubbed the spatiotemporal on-demand patch (SOP), the device is soft and thin like a Band-Aid, with an embedded computer chip that controls the whole process. Once a wireless signal is received an electric current is sent through the device, dissolving a thin gold coating on the microneedles to allow release of the drug in their reservoirs. In theory, multiple drugs could be loaded into the needles and released in sequence.

While the device is still at the research phase – so far it’s been tested in the skulls of mice – it holds potential to transform how chronic conditions are treated, says Bai. Patients could simply input their regimen into a computer and let the patch take care of the rest, administering the right dose at the right time automatically. In the long term, the hope is that it could also enable drug delivery into specific areas of the brain.

On-demand drug release

What’s novel about the SOP is the use of an electrical trigger to control drug release, Bai explains. The gold microneedle coating acts as a kind of gate: after receiving the wireless signal, it dissolves in about 30 seconds to a minute. Gold is biologically stable and is used here in such small amounts that it’s below the threshold of toxicity, he adds. Other types of patches with a triggered release rely on cues from inside the body, such as certain shifts in pH or temperature. Yet there’s only so much influence you can have over the environment around the device, says Bai. “Those devices are so responsive to the body that we lose control over them.” The SOP, on the other hand, allows individual reservoirs to be engaged at the press of a button. “Changes in temperature cannot allow such precise control,” he adds.

Labs elsewhere have looked into other external triggers for drug release, including UV or infrared light, magnetic fields, or specific movements in the body such as tension in certain muscles – all to varying degrees of success. Creating microneedles that respond to any stimuli is an emerging field of research and no solution has yet managed the leap from benchtop to clinic.

This is a crucial capability for patches meant for chronic use: if you want one patch to give multiple doses, you need to be absolutely sure that you can deliver them at the right time. In future, Bai hopes that the SOP could be used to administer combination regimens that not only involve multiple drugs but that require those drugs to be taken in a particular order – as can be the case in oncology.

While the team hasn’t yet tested the system with a programmed schedule of drug release, Bai says that their hardware is capable of it. “The device contains tens, if not hundreds, of reservoirs. Each reservoir can be individually prepared, loaded with specific drugs, and be individually controlled… We haven’t demonstrated it in our paper but that’s the next step.”

Reaching the brain

In mice, the SOP was placed directly over the relevant region of the brain and delivered the drug straight to its target. If it could do the same for people, this may well transform how we treat neurological diseases.

Getting drugs into the brain is especially tough because of how well it’s protected: there’s the skull and layers of membrane cushioning it from the outside, plus the blood-brain barrier, a tightly packed interface of cells that determine which substances can pass from the blood through to the brain. Most drugs are denied entry.

By applying microneedles directly into the relevant tissues, the SOP allows you to bypass all of that, Bai explains. Plus, this ensures that the drug reaches its target without being diluted or causing any unwanted effects – for instance, by needing to travel through the bloodstream to get to a site further away. “Once those drugs reach other parts of the body, it generates an immune response and also tissue responses. Direct drug delivery could avoid these,” he says.

This could also be an alternative to invasive treatments such as deep brain stimulation, which is used to treat Parkinson’s. “It requires open skull surgery,” says Bai. “And it requires the patient to be awake… to generate feedback and stimulate the right location. Which I feel is definitely not an ideal situation.”

But we’re still a way away from understanding how the SOP could be applied on patients. “This paper is trying to demonstrate a concept,” says Bai. “In the long term, we’re aiming for neurological diseases.”

In the meantime, the team also plans to explore how their patch could be used on the skin. Because the needles required to penetrate the skull are longer than those needed to get under the skin, Bai is optimistic that the technology could one day be used transdermally – though perhaps with minor modifications.

Richard Guy, professor of pharmaceutical sciences at the University of Bath, says that he’s yet to see a system such as the SOP – using metal-coated needles that are triggered electrically – used in transdermal microneedle patches.

A key challenge with skin patches is ensuring that the correct dose reaches its target, he explains. Because microneedles can only deliver limited volumes, the patch would need to be inserted near enough to the drug target to prevent the dose from being diluted. To reach a target further afield, “there will be a huge dilution effect of the drug once it gets out of the microneedles and enters the bloodstream”, Guy says.

Here, one area Bai and his team intend to look into is insulin delivery for diabetic patients. Microneedle patches “will release the burden on the patient to always think about injecting the insulin at a certain time of day and struggling with that precise dose”, he says.

From mice models to market

If you were to head to the skin section of a pharmaceutical science meeting today, chances are that you’d see a bunch of enthusiastic postdocs who were mostly working on microneedles, says Guy. “This has been going on for a while. The microneedles field is now over 20 years old.”

Yet despite generating so much interest, there isn’t a single microneedle patch approved for use in clinics, he adds. This is partly down to the challenges in creating devices like these: you need to demonstrate to regulators that you can reproducibly deliver the right dose. On the skin, this can be especially difficult as it’s not a flat surface. “You put in an array of needles, some of them penetrate the skin but others don’t. The problem is you get variability in terms of the dose delivered,” says Guy.

But that’s not to say that there aren’t any solutions on the horizon. Guy believes that we’re “getting close” to having the first microneedle patch approved for use, which he predicts will be a vaccine. This is because they are given infrequently, generally require a small dose, and have a large therapeutic window – all of which may make it easier to demonstrate safety and efficacy to regulators.

Over in North Carolina, Bai and his team have filed a provisional patent for the SOP and will be looking to develop their research over the next two years. Through animal models, they aim to further validate their system and investigate whether it could boost drug efficacy. “After that, there’s the possibility for translation,” he says. “We want to see the technology we have been working on help address the grand challenges in the medical world.”