Ultrasound 'microjets' enable targeted treatment of neurological conditions
A new discovery involving ultrasound “microjets” could improve the treatment efficacy of therapeutics targeted at neurological conditions.
It can be difficult to deliver targeted therapy to the brain due to its protective blood brain barrier (BBB), which only allows nutrients and oxygen to pass through. In the past, experts have proposed the use of focused ultrasound to help penetrate the BBB.
Eventually, researchers discovered that microscopic bubbles injected into the bloodstream at the same time as different drugs enabled providers to deliver precision treatment. After the microbubbles are injected, doctors use ultrasound at the target site to activate them. This causes the microbubbles to vibrate, creating a pore on the cell membrane of the blood vessel, which allows treatment to pass through and reach the treatment site of choice.
Until recently, little was known about exactly what enabled therapeutics to pass through with the microbubbles, making it challenging to develop effective treatments. Now, a group of researchers at ETH Zurich—a public research university in Switzerland—believe they have uncovered the underlying mechanisms behind it.
“We were able to show that under ultrasound, the surface of the microbubbles loses their shape, resulting in tiny jets of liquid, so-called microjets, which penetrate the cell membrane,” explained Marco Cattaneo, doctoral student and lead author of the study.
In the past, it was difficult to visualize how the pores on the cell membrane form due to their microscopic size. The team had to build their own specialized microscope with a magnification of 200x and connect it with a high-speed camera to get a detailed view of the process.
The team tested their microscope by simulating a blood vessel wall using endothelial cells grown on a plastic membrane. The membrane was placed in a box with clear walls filled with saline and a model drug so the team could observe their reaction to a microsecond-long ultrasound pulse.
The ultrasound created tiny microjets that were able to safely and effectively penetrate the blood vessel wall, moreso than any previous methods that have been tested thus far, the team suggested.
“Our work clarifies the physical foundations for targeted administration of drugs through microbubbles and helps us define criteria for their safe and effective use,” leader of the research Outi Supponen, a professor at the Institute of Fluid Dynamics, explained. “Additionally, we were able to show that just a few pulses of ultrasound are enough to perforate a cell membrane. This is also good news for patients.”
Their findings could pave the way for improving focused ultrasound treatments involving microbubbles. For example, the makeup of the coating of the microbubbles could be further improved, which would make it easier for the microjets to form.
Learn more about the findings here.