Our brain is constantly working to keep the body functioning and, therefore, requires the utmost protection. In addition to a thick skull, the blood-brain barrier (BBB), a natural protective membrane, prevents microscopic intruders such as toxins and pathogens from entering the nervous system.
Unfortunately, this also limits medical treatment for neurological disorders, including Alzheimer’s, Parkinson’s, brain tumors, and ALS (amyotrophic lateral sclerosis). But recent developments in medical physics have introduced ultrasound-activated microbubbles that temporarily open the BBB, allowing targeted drug delivery. This innovation could revolutionize healthcare by enhancing treatment precision and reducing side effects.
To better understand the physical mechanisms behind microbubble drug delivery, researchers from ETH Zurich, Switzerland, published their findings in Nature Physics, offering insights into the future of targeted therapies.
Targeted Drug Delivery
The BBB consists of tight junctions that connect endothelial cells — the cells lining the inside of blood vessels. It selectively allows certain nutrients and oxygen to pass through while restricting many other substances. Drugs that cross the BBB are typically fat-soluble molecules that diffuse directly through cell membranes, whereas larger or water-soluble molecules face significant challenges.
Most chemical drugs intended to treat central nervous system disorders struggle to penetrate the BBB due to their chemical properties. As a result, they often have low therapeutic efficacy while accumulating in other organs and tissues, increasing the risk of side effects.
To overcome this challenge, researchers have been exploring advanced methods for targeted drug delivery. Microbubbles, which encapsulate therapeutic compounds in gas form, offer a promising solution. Administered via the bloodstream, they travel to the targeted area and release their cargo into the brain when triggered by ultrasound. This makes them the only known noninvasive, localized, and reversible method for opening the BBB and delivering drugs directly to the brain.
However, the precise physical process by which microbubbles facilitate drug transport remained unclear — until now.
Read More: Inside the Human Brain
Microbubbles and Microjets
Microbubbles, which are smaller than red blood cells, are stabilized by a coating of fat molecules. When exposed to ultrasound at the target site, these bubbles temporarily create tiny pores in the BBB’s cell membrane, allowing drugs to pass through. However, the exact mechanism behind this process had not been fully understood.
Observing these interactions is extremely challenging, as microbubbles measure only a few micrometers in diameter (a micrometer is a thousandth of a millimeter) and vibrate millions of times per second under ultrasound.
To capture this process in detail, the researchers developed a specialized microscope with 200x magnification and integrated it with a high-speed camera capable of recording up to 10 million images per second.
To simulate the interaction between microbubbles and the BBB, they constructed a model consisting of endothelial cells on a plastic membrane submerged in a saline solution. After introducing microbubbles containing a model drug, they applied a microsecond-long ultrasound pulse.
“We were able to show that under ultrasound, the surface of the microbubbles loses its shape, resulting in tiny jets of liquid, so-called microjets, which penetrate the cell membrane,” Marco Cattaneo, a doctoral student and first author of the study, explained in a press release.
These microjets, moving at an astonishing speed of 200 kilometers per hour (about 124 miles per hour), puncture the cell membrane with pinpoint precision while keeping the cell intact. The process is highly efficient, as the bubble remains intact after each jet formation, enabling continuous drug release with every ultrasound cycle.
Observing in Detail
This laboratory setup allows researchers to observe cell-microbubble interactions in unprecedented detail. Moving forward, scientists aim to optimize the frequency and pressure of ultrasound, as well as the size and coating of microbubbles, to maximize therapeutic efficacy while ensuring patient safety.
“Our work clarifies the physical foundations for targeted administration of drugs through microbubbles and helps us define criteria for their safe and effective use,” said Outi Supponen, a professor at the Institute of Fluid Dynamics in Zurich, in the press release.
Future studies will further refine this technology, potentially expanding its applications beyond neurodegenerative diseases to include conditions such as heart attacks and atherosclerosis.
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Article Sources
Our writers at Discovermagazine.com use peer-reviewed studies and high-quality sources for our articles, and our editors review for scientific accuracy and editorial standards. Review the sources used below for this article:
Nature Physics: Cyclic jetting enables microbubble-mediated drug delivery
StatPearls: Anatomy, Head and Neck: Blood Brain Barrier
Having worked as a biomedical research assistant in labs across three countries, Jenny excels at translating complex scientific concepts – ranging from medical breakthroughs and pharmacological discoveries to the latest in nutrition – into engaging, accessible content. Her interests extend to topics such as human evolution, psychology, and quirky animal stories. When she’s not immersed in a popular science book, you’ll find her catching waves or cruising around Vancouver Island on her longboard.
