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Successful Delivery of Glioblastoma Drug Across Blood-Brain Barrier in Mice Models

Researchers from Northwestern University apply for FDA approval of novel treatment for patients with recurrent glioblastoma.

The anatomical structure of the brain poses various challenges in drug delivery of treatment of glioblastoma, the most aggressive form of brain tumours. First would be crossing the blood-brain barrier that prevents the entrance of toxins to the brain from blood and another challenge is the conventional formulation for the current drug is toxic to the brain.

“Glioblastoma currently has no cure, and when the tumour recurs there are not many treatment options,” said the principal investigator for this study, Dr. Adam Sonabend, an assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician. “We urgently need effective new treatments.”

To tackle these issues medical scientists from Northwestern University have developed a novel technology in opening the blood-brain barrier with an implantable ultrasound, to facilitate drug delivery to brain tumours in mice.

The tiny ultrasound would be implanted during surgery into a window in the skull that does not contain bone. It is used in combination with microscopic gas bubbles injected into the blood at the same time the ultrasound begins. When the bubbles hit the sound waves, these vibrate and mechanically disrupt the blood-brain barrier. The opening is immediate, allowing penetration of the drug molecules. The blood-brain barrier opening is reversible and lasts for several hours after the sonication. The ultrasound emitter remains in the skull for repeated delivery of the drug.

The ultrasound technology may have broader benefits. “This ultrasound technology now will enable us to use many agents established in other cancers for patients with brain tumours,” said co-investigator Roger Stupp, chief of neuro-oncology and the Paul C. Bucy Professor of Neurological Surgery at Feinberg.

Besides the delivery of the cancer drug, the team also tested a new formulation of the conventional drug – paclitaxel. Their new formulation new dissolves the drug in albumin as opposed to cremophor which was known to result in brain toxicity.

From the study, opening of the blood-brain barrier with an ultrasound increased the concentrations of this paclitaxel in the brain by five-fold. The study also showed that the brain tumour-bearing mice live much longer when treated with the powerful cancer-fighting drug paclitaxel, and survival was even further extended when treated in combination with ultrasound to open the blood-brain barrier.

Moving forward the scientists are now apply for approval by the U.S. Food and Drug Administration to launch a clinical trial to test the concept of a new formulation of paclitaxel in combination with their novel ultrasound technology in patients. The trial will aim to determine the safety and whether it will prolong survival of patients with brain cancer.

The study was published in December 2019 on Clinical Cancer Research, a journal of the American Association for Cancer Research. [APBN]