July 10, 2023 – Scientists have developed a biodegradable implant that helps chemotherapy drugs penetrate the blood-brain barrier and directly attack brain tumors.
It is the most recent advance in a rapidly growing field that uses ultrasound – high-frequency sound waves which are imperceptible to humans – to fight cancer and other diseases.
The problem the researchers are studying is the blood-brain barrier, a virtually impenetrable lining of blood vessels that stops harmful molecules from the blood from entering the brain. But this lining may also prevent chemotherapy drugs from reaching cancer cells.
The scientists subsequently implanted one-square-centimeter implants within the skulls of mice directly behind the tumor. The implants generate ultrasound waves that loosen the barrier and permit the drugs to succeed in the tumor. Healthy tissue shouldn’t be damaged by the sound waves.
“You inject the drug into the body and turn on the ultrasound at the same time. You hit the tumor area exactly every time,” said lead study writer Thanh Nguyen, PhD, associate professor of mechanical engineering on the University of Connecticut.
The drug utilized in the study was paclitaxel, which normally has difficulty crossing the blood-brain barrier. The tumors shrank and the mice lived twice so long as untreated mice. Six months later, the mice showed no negative health effects.
Breaking through the blood-brain barrier
The biodegradable implant is fabricated from glycine, an amino acid that can also be highly piezoelectric, meaning it vibrates when exposed to an electrical current. To create it, the researchers grew glycine crystals, smashed them into pieces, and at last used a process called electrospinning, which involves applying a high electrical voltage to the nanocrystals.
Voltage is shipped to the implant via an external device. The resulting ultrasound causes the closely intertwined cells of the blood-brain barrier to vibrate, stretching them and creating space for the formation of pores.
“This allows very small particles to penetrate, including chemotherapy drugs,” said Nguyen.
His previous biodegradable implant broke apart under the force, but the brand new glycine implant is more flexible, stable and highly piezoelectric. It might be implanted in a patient after surgery to remove a brain tumor to proceed treatment of any remaining cancer cells. The implant dissolves harmlessly within the body over time and doctors can control its lifespan.
A brand new wave of ultrasound applications
Nguyen’s study builds on similar efforts, including a recent clinical study a non-biodegradable implant for the treatment of brain tumors. Ultrasound can focus energy on precise targets within the body.
It's like “using a magnifying glass to focus multiple beams of light on one spot and burn a hole in a leaf,” said Dr. Neal Kassell, founder and chairman of the Focused Ultrasound Foundation. This approach preserves the encompassing normal tissue, he said.
Doctors now know of greater than 30 ways by which ultrasound interacts with tissue – from destroying abnormal tissue to delivering drugs more effectively to stimulating an immune response. Ten years ago, only five such interactions were known.
This opens the door to treating a “broad spectrum of medical disorders,” from neurodegenerative diseases reminiscent of Alzheimer's and Parkinson's to difficult-to-treat prostate and pancreatic cancers and even addiction, Kassell said.
Kassell sees focused ultrasound in its place (or addition) to surgery, chemotherapy, immunotherapy or radiotherapy for the treatment of brain tumors. Implants have now shown “the effectiveness of opening the blood-brain barrier,” he said.
Nguyen's team plans to check the security and effectiveness of their implant in pigs next. Eventually, Nguyen hopes to develop a patch with a series of implants that focus on different areas of the brain.