Microbubbles and ultrasound open the blood–brain barrier to administer drugs

Dominic Kleinknecht

Eberhard-Karls-University Tübingen

The brain is the most important part of our body and is thus especially protected against potential pathogens crossing over from the blood stream via the blood-brain-barrier. While this is helpful against bacteria, viruses, or other pathogens, the blood-brain-barrier also blocks medicines from entering the brain, preventing potential treatments of neurodegenerative diseases such as Parkinson’s or Alzheimer’s. Overcoming this seemingly impenetrable barrier that blocks 98% of available drugs has been a challenge for many years, with the only method at hand being the use of ultrasound and lipid-coated, innocuous gas microbubbles: The ultrasound, which is focused on a specific region of the brain, makes the microbubbles oscillate in the blood. This causes them to grow in size, and after reaching a critical size the blood-brain barrier opens up near them and allows the medicine to enter the brain. However, this means the microbubbles circulate through the entire body, potentially causing adverse effects in other organs. Now, researchers at the Ultrasound Elasticity Imaging Laboratory (UEIL) at Columbia University have improved this technology to allow for brain-specific drug administration. They managed to incorporate the active parts of the drug into the lipid coating of the microbubbles, which means that the drug will only be released after the microbubbles are burst with ultrasound in the brain, allowing for a controlled drug release to the brain tissue while being non-invasive, reversible, and completely safe. The researchers had demonstrated the improved technology in mice, and applying the technique to treat Parkinson’s in mice has already provided promising initial findings. However, further research needs to be done, and evaluating the technology should be expanded to monkeys and eventually humans before it will be ready as a therapy for neurodegenerative diseases or strokes.

 

C. Sierra, C. Acosta, C. Chen, S.-Y. Wu, M. E. Karakatsani, M. Bernal, E. E. Konofagou. Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening. Journal of Cerebral Blood Flow & Metabolism, 2016; DOI: 10.1177/0271678X16652630