Researchers at the Technical University of Munich (TUM) have demonstrated a prototype drug that can release three active ingredients at different times and in sequence. The key to this unusual and useful ointment is artificial DNA, which breaks down at precise intervals.

Certain illnesses often require multiple drugs to be administered in a very specific order, but putting the responsibility on patients to take the right pills at the right times can lead to missed doses and less effective treatments. In the past, drugs or topical creams have been made to release active ingredients on a time delay, but these aren't always reliable either.

The TUM team says it's solved this problem with a new drug structure that can release different components at different times. This structure could be put to work to make drugs that have multiple effects as they're needed, without people having to remember to take several drugs at specific times.

"For example, an ointment applied to a surgical incision could release pain medication first, followed by an anti-inflammatory drug and then a drug to reduce swelling," says Oliver Lieleg, co-lead author of the study.

As a proof of concept, the researchers created a hydrogel that released different nanoparticles in order. For this test, silver particles were released first, then iron oxide particles, and then gold. The trick is to bind them all together using meshes of artificial DNA, specially designed to break down at different rates when exposed to the right triggers.

At first, the clusters of particles and DNA are too big to move around in the hydrogel. This is by design, keeping them from releasing their payloads while the ointment is still in a tube. They're waiting for the first trigger – salt – which indicates that the hydrogel has been applied to skin.

Once the right salinity level is reached (in this test case, the team used a solution that has a similar salinity to the human body), the silver particles separate from the DNA meshes and drift to the surface. The other particles aren't affected by the salinity, so they stay attached to the DNA, waiting for their turn. And that comes soon – after the DNA structures that were holding the silver particles in place dissolve, they next break down the DNA fragments holding the iron oxide particles. And finally, the gold particles can only be released after the DNA fragments holding the iron particles are broken down.

Overall, this design ensures that the different types of particles have to be released in the desired order. In practice though, the silver, iron and gold particles would be replaced with different drug payloads – these were chosen simply to test the concept.

"The consistency of ointments makes them the most obvious solution for a hydrogel-based approach," says Lieleg. "However, this principle also has the potential to be used in tablets that could release several effective ingredients in the body in a specific order."

The research was published in the Journal of Controlled Release.

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