Researchers Discover Way To Allow Drugs To Penetrate Through The Blood-Brain Barrier
Biomedical engineers from University of Connecticut have designed a non-toxic, biodegradable device that can help medication move from blood
vessels into brain
tissues, a route traditionally blocked by the body's defense mechanisms. The research findings are published in the PNAS Journal.
Typically, blood vessels in the brain
are lined by cells fitted together tightly, forming a so-called blood-brain barrier
, which walls off bacteria and toxins from the brain itself. But that blood-brain barrier
also blocks medication for brain diseases such as cancer.
Dr Thanh Nguyen, a biomedical engineer at UConn told Thailand Medical
News, "A safe and effective way to open that barrier
is ultrasound. Ultrasonic waves, focused in the right place, can vibrate the cells lining blood
vessels enough to open transient cracks in the blood-brain barrier
large enough for medication to slip through. But the current ultrasound
technology to do this requires multiple ultrasound
sources arrayed around a person's skull, and then using an MRI machine to guide the person operating the ultrasounds
to focus the waves in just the right place. It's bulky, difficult, and expensive to do every time a person needs a dose of medication.”
Now, there is another way: implanted devices can apply ultrasound
locally in the brain
. It's much more precise and repeatable, but most ultrasound transducers contain toxic materials such as lead. And they have to be removed after use, which requires surgery and can harm brain
Dr Nguyen knew there could be a better tool for this. His lab specializes in piezoelectric
convert physical strain, such as being bent or compressed, into electricity, and vice-versa. They are the perfect material for transducers, which use electricity to create vibration.
Dr Nguyen's graduate student Eli Curry figured out how to spin poly L-lactic acid (PLLA), a biodegradable polymer, into tiny nano-fibers just 200 nanometers wide and several tens to hundreds of microns long. When the researchers applied a high voltage during this spinning process, the fibers stretched and aligned. Thus aligned, they could be woven into a mesh. And the alignment of the fibers heightened their piezoelectric
response, allowing the nano-fiber PLLA to vibrate more powerfully using much less electricity than a regular film of the polymer would have. These highly piezoelectric
nanofibers enable the researchers to fabricate a sensitive biodegradable implanted sensor which can wirelessly measure intra-organ pressures. The same sensor can also act as an ultrasonic transducer.
Poly L-lactic acid (PLLA) is often used for dissolving surgical sutures and is a very safe, bio-compatible material. Accordingly, when graduate student Thinh Le impl
anted the PLLA transducers into mice, he found that the transducers were safely biodegraded. Most significantly, the device can generate well-controlled ultrasound
to locally open the blood-brain barrier
, consequently helping medications injected into the blood
access the brain
tissue. This ultrasound
device can even act as an speaker to generate audible sound or play music.
Dr Nguyen added, "This is an exciting proof of concept; it's the first biodegradable transducer made of common and safe medical materials,"
He says the team still needs to work out how to optimize the intensity to get good cracks in the blood-brain barrier
, wide enough for large drug molecules to pass through, without damaging the blood
vessels or the brain
. And for the device to be approved for use in humans, it would need to be tested for longer periods of time, in animals larger than mice.
Reference : Eli J. Curry et al. Biodegradable nanofiber-based piezoelectric transducer, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1910343117