A Delicate Crossing: Controller Developed to Open The Blood-Brain Barrier With Precision

Source: Brigham and Women’s Hospital

Summary: Researchers in a new advancement have developed a system in preclinical models to open the blood-brain barrier with high precision for drug delivery.

The blood-brain barrier (BBB) is a highly selective semipermeable membrane which surrounds the brain. BBB separates the blood from the brain and extracellular fluid in the CNS (central nervous system). BBB may offer protection to the brain but in some cases, it is important to get past the barrier to deliver key drugs for treating brain. Researchers from Brigham and Women’s Hospital are examining a way to loosen the blood-brain barrier temporarily to deliver drugs with the help of microbubbles. in a new advancement they have developed a system (closed-loop controller) in preclinical models to open the blood-brain barrier with high precision for drug delivery. The research findings are published in the journal Proceedings of the National Academy of Sciences.

Closed-loop Controller to open blood brain barrier for drug delivery

Representation of the drug delivery system. Serving as the acoustic indicator of drug delivery dosage, the microbubble emission signal y(t) is used to find the expected controller output u(f) which is fed back to help control ultrasound transducer transmission. Credit: Tao Sun, Brigham and Women’s Hospital

A rat model was used to develop the closed-loop controller – a system which can give the researchers a metaphorical window into the brain. Sensors which act like secondary microphones are placed outside of the brain which helps the research team to listen to ultrasound echoes bouncing off the microbubbles and determine the stability of bubbles. They could adjust the ultrasound input by fine-tuning and stabilize bubbles, excite them to open the BBB for delivering a drug of a predefined dose. The method was tested in healthy rats as well as an animal model of glioma brain cancer. More research is needed to make the technique suitable for humans. This could offer improved safety and efficacy control for the clinical trials in humans.

Lead author, Tao Sun said, “We want to be able to monitor our ability to open the blood-brain barrier in real-time by listening to echoes – this could give us immediate information on the stability of the microbubbles oscillations and give us fast, real-time control and analysis.”

More Information: Tao Sun et al, “Closed-loop control of targeted ultrasound drug delivery across the blood-brain/tumor barriers in a rat glioma model”, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1713328114


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