Targeted drug delivery to the brain via the bloodstream

The targeted treatment of brain diseases such as Alzheimer's, Parkinson's and brain tumours is a major challenge for modern medicine. The central problem is the blood-brain barrier. This natural barrier protects the sensitive brain from harmful substances, but also prevents the passage of many potentially effective drugs. As a result, direct access to diseased brain regions is often impossible.

Researchers around the world are therefore searching for new approaches to cross this barrier safely and efficiently. One promising approach comes from ETH Zurich: ultrasound-activated microbubbles. These gas-filled microbubbles circulate in the bloodstream until they are activated by ultrasound at the target site. This causes tiny pores to form in the cell membranes of the blood vessel walls, allowing drugs to enter in a targeted manner.

For a long time, it was unclear exactly how these pores in the cell membrane were formed. Now, for the first time, researchers working at the Institute of Fluid Dynamics have been able to visualise the mechanism. Using a microscope with 200x magnification and a high-speed camera that takes up to ten million images per second, they captured the ultrafast movements of the microbubbles from a new perspective. The results of the research were recently published in Nature Physics.

To mimic natural conditions in the body, the researchers developed an in-vitro model, growing endothelial cells on a plastic membrane floating in a saline solution. Microbubbles rose and came into contact with the cells. A brief ultrasound pulse set the microbubbles in vibration. At a certain pressure (around 100 kPa), the microbubbles deformed severely, producing jets of fluid called microjets. These hit the cell membrane at high speed (up to 200km/h) and selectively opened it without destroying it.

A key advantage of this method is that the low ultrasound pressure is similar to the atmospheric pressure to which we are exposed every day. The procedure is therefore low-risk and could be particularly suitable for sensitive tissues such as the brain.

The findings not only provide new insights into the physical principles of the method, but also open up new perspectives for medical applications. In particular, they may provide a new, minimally invasive therapeutic option for neurodegenerative diseases such as Alzheimer's and Parkinson's, as well as for brain tumours.