Researchers at Washington University in St. Louis have developed a new method to bypass the blood-brain barrier and deliver drugs to the brain, which could be particularly useful in difficult-to-treat brain tumors. The technique involves administering drugs through an intranasal spray, meaning that the drug can travel directly into the brain along the trigeminal and olfactory nerves. Then, the researchers can use focused ultrasound to allow the drug to penetrate and accumulate in deeper layers of the tissue, and exert therapeutic benefit at the ultrasound-targeted region.
Drug therapy for brain tumors is challenging, because the blood-brain barrier makes it difficult for drugs to penetrate the blood vessels that line the brain. To address this, this research group thought about a different route of delivery, through the nerves in the nose, that could bypass the blood-brain barrier.
“At the beginning, I couldn’t even believe this could work,” said Hong Chen, a researcher involved in the study. “I thought our brains are fully protected. But these nerves actually directly connect with the brain and provide direct access to the brain.”
The researchers developed a method to target the drug to specific brain regions, once it is in the brain. The method involves a patient using an intranasal spray to deliver a drug to the nerves that are present in the nasal cavity, which then transport the drug directly into the perivascular space in the brain.
The researchers can then target intravenously injected microbubbles (which could be injected into a blood vessel elsewhere, such as in the arm, for example), using focused ultrasound at the brain region they wish to treat. The ultrasound causes the microbubbles to oscillate, which expands and contracts the blood vessels and the perivascular space surrounding the blood vessels. This allows the drug to penetrate through the perivascular space, resulting in local accumulation of the drug at the ultrasound-targeted region.
So far, the researchers have tested the technique in mice but aim to optimize it further to assess its potential in treating diffuse intrinsic pontine gliomas, a childhood cancer with limited treatment options.
Here’s a video demonstrating the technique:
Study in Journal of Controlled Release: Focused ultrasound combined with microbubble-mediated intranasal delivery of gold nanoclusters to the brain…