The blood-brain barrier - the semi-permeable membrane that surrounds the brain - offers important protection for a delicate organ, but in some cases, clinicians need to get past the barrier to deliver vital drugs to treat the brain.
Researchers are investigating a way to temporarily loosen the blood-brain barrier to deliver drugs with the assistance of microbubbles. In a new advancement, they have developed a system in preclinical models that offers a finer degree of control - and, therefore, safety - in opening the barrier. Their findings are published in The Proceedings of the National Academy of Sciences.
"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," said lead author.
In the lab, the research team used a rat model to develop a closed-loop controller - a device that can give them a metaphorical window into the brain. By placing sensors on the outside of the brain that act like secondary microphones, the research team could listen to ultrasound echoes bouncing off the microbubbles to determine how stable the bubbles were. They could then tune and adjust their ultrasound input instantly to stabilize the bubbles, excite them to open the barrier, and deliver a drug of a predefined dose, while maintaining safe ultrasound exposure.
Tests in the normal brain and in the F98 glioma model in vivo demonstrated that this controller enables reliable and damage-free delivery of a predetermined amount of the chemotherapeutic drug (liposomal doxorubicin) into the brain. The maximum concentration level of delivered doxorubicin exceeded levels previously shown (using uncontrolled sonication) to induce tumor regression and improve survival in rat glioma.
Further research will be needed to adapt the technique for humans, but the approach could offer improved safety and efficacy control for human clinical trials, which are now underway in Canada.
Controlled opening of the blood-brain barrier with precision
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