Biodegradable ultrasound opens the blood-brain barrier

A new, biodegradable ultrasound far more powerful than previous devices could make brain cancers more treatable, University of Connecticut researchers report in Science Advances. The study was supported by the U.S. National Science Foundation.

When someone is diagnosed with a cancerous brain tumor, it is usually removed surgically, and then chemotherapy is used to mop up the remaining cancer cells left behind. But brain cancers are particularly resistant to chemotherapy because the lining of the blood vessels prevents large molecules that could potentially harm the brain from passing through.

These also prevent useful chemo-drugs and other therapeutics from killing brain cancer cells and treating other brain diseases. One safe and effective way to get past the blood-brain barrier, as it’s known, is to use ultrasound to jiggle cells enough to open pores large enough to allow the medicine to pass through.

“This team’s creative solutions to a critical human problem demonstrate the power of integrating engineering with medicine”

– Kathryn Jablokow

But getting ultrasound through the thick human skull is not easy. Generally, multiple powerful ultrasound devices must be strategically placed around the skull and carefully focused on the site of the tumor with an MRI machine immediately after chemotherapy is administered in the hospital.

“We can avoid all that by using an implanted device” in the brain itself, says biomedical engineer Thanh Nguyen. “We can repeatedly use it, allowing chemo to penetrate the brain and kill off tumor cells.” There is already an implantable ultrasound device commercially available, but it is made of ceramic materials that are potentially toxic and must be surgically removed after treatment is finished.

The researchers came up with a novel solution. They grew glycine crystals and then intentionally shattered them into pieces just a few hundred nanometers in size. They then spun them (under high voltage in a process called electrospinning) with polycaprolactone (PCL), a biodegradable polymer, to make piezoelectric films composed of nanofibers of glycine and PCL.

Under a small driven voltage, the film can generate ultrasound at 334 kilopascals, about the same as a ceramic ultrasound brain implant. The team coats the glycine-PCL film in other biodegradable polymers to protect it. Poly-L-Lactide, one possible coating, takes approximately six weeks to break down.

The team has done a six-month safety look at the device implanted inside the brain and found it had no adverse effects on the health of the mice. They will now begin testing safety and efficacy in large animals.

“This team’s creative solutions to a critical human problem demonstrate the power of integrating engineering with medicine,” says Kathryn Jablokow, a program director in NSF’s Directorate for Engineering.

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