Just shoot

The advance of microneedles for pain-free jabs

By Bart Braun

An array of tiny needles works better than one large syringe. PhD candidate Koen van der Maaden thought up a smart way of transferring vaccines to microneedles.

Vaccines of the future look like Velcro: you can only see that needles are still involved when you look more closely. Instead of the large, single syringes we use now, you will be injected with dozens of little needles. And they are considerably smaller: depending on the type, they can measure between one and one-tenth of a millimetre.
Injections will be painless, requiring much smaller amounts of the drug or vaccine. In an ideal world, a manufacturer could produce huge sheets of stickers containing microneedle vaccines which anyone could adhere to his or her body. This means the whole world could be vaccinated without the aid of nurses. Nonetheless, we’re not there yet, as pharmacologist Koen van der Maaden discovered. Van der Maden was awarded his doctorate last Wednesday for his work on the use of microneedles for vaccinations. “Everyone uses different levels of force to push the needles into the skin, which affects how well the needles inject. I asked fifteen volunteers to stick a patch onto their skin and compared their attempts to a device that always uses the same amount of force and speed. Only thirty to eighty per cent of the needles were actually injected into the skin when delivered manually, which obviously had an impact on how much of the vaccine was administered. There was much less variation when an applicator was used and the efficiency was much higher, as much as 98 per cent. So you really do need the equipment.”
Van der Maaden assures us that the price is almost the same: “In theory, an applicator uses a tiny spring, which pens have too. How much does a pen cost? A few cents? And you just shoot – bang – the needles into the skin.”
Van der Maaden describes all sorts of different kinds of microneedles in his doctoral thesis. Some are etched from silicon, manufactured in a similar way to computer chips. He even made his own hollow needles from quartz, protecting his face with a sort of welding mask against the lethal hydrofluoric acid required for the process. “You can also make soluble needles: first you make a mould, then allow the liquid with the medicine or vaccine to solidify. Your drug is the actual needle, which slowly disappears in the skin. The disadvantage is that you can never make them as sharp as metal, quartz or silicon.”
Once the needles have penetrated the stratum corneum, they reach the epidermis underneath, which is full of antigen-presenting cells. Those cells tell the immune system what to attack. You see, our skin is not some kind of leather condom to keep all the stuff on the inside of our bodies from falling out – it is a major organ and part of our immune system. This means that microneedles are particularly suitable for administering vaccines, either by using hollow needles through which the vaccine can flow or by covering the needles with a vaccine. Van der Maaden has designed a smart way of producing the latter.
“Normally, a thick layer of the vaccine surrounds the needles but the disadvantage of that is that the needles are not very sharp, so they don’t penetrate as well and consequently release less vaccine.” Instead, Van der Maaden uses ultra-thin layers: the vaccine remains adhered to the needle until it enters the patient’s skin where it is released. To do that, he first adhered a very thin layer of molecules that, depending on the pH, have a different electrical charge. “Pyridine groups have a positive charge in a slightly acidic environment. The vaccine I wanted to use has a negative charge so the needles that have been treated with pyridine are stored in an acidic environment and then the vaccine is added, making it an efficient way of getting it on the needles.” However, the epidermis is not acidic, but slightly alkaline. “So the pyridine groups lose their positive charge once they’re inside the skin, releasing the vaccine there.”
The first microneedles were trialled back in the nineties but their use is gradually advancing. One type of flu vaccine on a single microneedle is available in America. “There is also a cosmetic product that uses microneedles which the manufacture claims combats wrinkles”, says Van der Maaden sceptically.
“Now, we’re in the first stages of testing vaccines on microneedles on human volunteers. The American Food and Drug Administration, which calls the shots on medicines allowed onto the American market, announced their opinion of microneedles for the first time this year. They think it is important that the results of experiments can be reproduced and that no needles are left in the skin after the vaccination. Although the needles probably pop out when the muscles are flexed, we first have to prove that they actually do.”

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Just shoot

An array of tiny needles works better than one large syringe. PhD candidate Koen van der …