Nasal spray and ultrasound team up for direct-to-brain drug delivery
The blood-brain barrier is an effective shield for our most vital of organs, and while that's great when it comes to infection, it's not so helpful when you're trying to get drugs in there. Recent research has found that nasal sprays could bypass the barrier and deliver drugs directly to the brain, and now the team has developed a way to use ultrasound pulses to drive the drugs to where in the brain they're needed.
Last year, researchers out of Washington University in St. Louis showed that nanoparticles sprayed into the nose can bypass the blood-brain barrier by way of the olfactory and trigeminal nerves. That's impressive, but "the brain" is a very vague delivery address for drugs. Plus, the drugs have trouble passing from the perivascular space (the area surrounding blood vessels) into deeper tissue where they can do their work.
So, the team has now developed a way to drive nanoparticles and drugs to specific parts of the brain. Known as focused ultrasound with intranasal delivery (FUSIN), the technique starts with the same nasal spray of nanoparticles as before. Then, an ultrasound contrast agent – essentially a mixture of microbubbles – is injected normally. Finally, an ultrasound wave is applied to the desired part of the brain, in this case the brain stem.
When the microbubbles pass through the ultrasound waves, they begin to expand and contract, which in turn pumps the nanoparticles towards that location. As they reach the pulsating microbubbles, the drugs are "thrown" out of the perivascular space into the tissue where they're needed most.
Not only does that improve the effectiveness of the drug by targeting the right area, it reduces the amount that builds up in other parts of the body which can cause unwanted side effects.
The researchers tested the concept by introducing gold nanoclusters into the nasal passages of mice, then applying the ultrasound pulses to the animals' brain stems. The technique was successful, and when the team checked the other organs via PET scan, they found minimal build-up of the particles in the lungs, liver, spleen, kidney and heart.
The team is trying to develop the method to fight a specific brain disease known as diffuse intrinsic pontine glioma (DIPG), a rare but deadly form of cancer found in children. The next steps, the researchers say, are to test how well the FUSIN technique works in delivering chemotherapy drugs to the brain stem of affected patients.
The research was published in the Journal of Controlled Release. The team describes the work in the video below.