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Nanoparticles deliver drugs to the brain

Photo of Johan Agorelius, Alexander Dontsios Holmkvist and Jens Schouenborg (Photo: Tove Smeds)
“There are a number of neurological conditions, such as chronic pain, epilepsy and Parkinson’s disease, whose mechanisms we want to understand”, says Jens Schouenborg. On his left: Johan Agorelius, Alexander Dontsios Holmkvist. Photo: Tove Smeds

A new method that slowly releases drugs locally in the brain has been developed by researchers at Lund University in Sweden. The drug is encapsulated in nanoparticles and delivered to the brain tissue via flexible electrodes. The method has been tested on mice and published in the Journal of Nanobiotechnology among others – and was recently presented in a doctoral thesis.

The brain is both our most complex organ and the most difficult one to study. By developing flexible electrodes thinner than a human strand of hair, researchers at Lund University are working to find new methods capable of registering signals from the brain’s nerve cells in order to learn more about the brain.

“There are a number of neurological conditions, such as chronic pain, epilepsy, and Parkinson’s disease, whose mechanisms we want to understand better so we can treat them in the best way”, says professor Jens Schouenborg, who is leading the research team’s work.

Reducing unwanted activity

The idea is that these electrodes also will treat brain tissue responses locally.

One challenge has been that electrodes implanted into the brain tissue can cause a local loss of nerve cells and inflammation that potentially damage the brain. The nanoparticles that are introduced into the brain using the electrodes, can deliver the drug exactly where it is needed.

The method has been tested on mice, and the researchers observed that the drug reduces unwanted activity in the microglial cells, which function as the brain’s immune defense in case of a brain injury, and that no nerve cells were damaged by the electrodes.

The capability of releasing drugs over long time

“This method is an important piece of the puzzle that provides us better control over the environment and the tissue surrounding the electrode implant in the brain. We used the drug Minocycline, which has nerve-cell protective properties and targets the aspects of inflammation that we want to mitigate”, says Johan Agorelius, doctoral student at Lund University.

A thorough and time-consuming research collaboration underpins the development of the drug-releasing nanoparticles. One challenge has been to develop nanoparticles capable of releasing the drug over a long period of time, but it has also taken time to figure out exactly what dose should be used in the brain.

“The nanoparticles are absorbed by gelatin, which then dries and encapsulates the particles. The gelatin has the advantage of being hard when it is dry, but softens when introduced into the brain tissue. There, the gelatin dissolves and the nanoparticles are released locally. The particles then break down slowly and release the drug over a long period of time”, explains Alexander Dontsios Holmkvist, doctoral student at Lund University, who developed the nanoparticles.

Allowing the brain tissue to heal faster

The electrodes that the research team developed in previous studies are so flexible that they cannot even withstand the surface tension of water. To enable their introduction into the brain, they are embedded in gelatin. The research team has previously also shown that the brain tissue heals faster when the electrodes are coated in gelatin.

The method of releasing the drug locally means that the rest of the body does not have to be affected.

“Using nanoparticles enables a local release of medication exactly where you want it to be released. These are very low doses, a million times lower than what would be administered orally. No refill of the drug is required as it is released over such a long time”, says Jens Schouenborg, who believes the method could also be relevant for delivering medication locally to other soft tissues, such as local treatment of cancer. However, more studies are required before that becomes a reality. 

Publication in Journal of Nanobiotechnology“Local delivery of minocycline-loaded PLGA nanoparticles from gelatin-coated neural implants attenuates acute brain tissue responses in mice”

Doctoral thesis, Alexander Dontsios Holmkvist:
Nanoparticle-based drug delivery systems for neural interfaces – a novel approach for improved biocompatibility