Our trainees review webinars in their given fields and share abstracts to help colleagues outside their discipline make an informed choice about watching them. As our program bridges diverse disciplines, these abstracts are beneficial for our own group in helping one another gain key knowledge in each other’s fields. We are happy to share these here for anyone else who may find them helpful.
Noninvasive drug delivery to the brain using short pulses of ultrasound
Dr. James Choi, Department of Bioengineering at Imperial College London
January 25, 2022
Summary and Analysis by Taylor Jorgensen:
This webinar by Dr. James Choi shares recent advances in the field of drug delivery across the blood-brain barrier. Historically, neurological diseases such as Alzheimer’s and brain tumors have been difficult to treat pharmacologically. While most capillaries in the body are leaky, those found within the BBB are tight, acting as both transport and enzymatic barriers. More than 99% of drugs that are larger than 400 Dalton are unable to pass through the barrier.
One way to enhance drug delivery is by using focused ultrasound. This is a non-invasive procedure in which ultrasound waves are specifically pointed at a target region of approximately 3 cm3. Simultaneously the drug of choice is administered intravenously, along with microbubbles. While these two compounds spread throughout the circulatory system, only those particles within the ultrasound area are affected. The microbubbles vibrate according to the wavelength of the ultrasound, resulting in mechanical stimulation and opening of the BBB.
Dr. Choi notes that while there are clinical trials pending in France, Israel, Taiwan, and the United States, this technique still needs to be optimized. It has been shown that different pulse lengths and sequences allow for differential opening of the BBB. Recently his lab has found that a protocol of rapid and short ultrasound pulses results in better drug distribution, less damage, and more rapid return of barrier integrity. Using these parameters researchers have shown that biotin, metal complexes, bace1 inhibitors, dextran, and albumin can all pass through the BBB in mice. While the largest compound they have passed through the BBB is only 66 kDa, this greatly increases the amount of therapeutic compounds that could be used.
This seminar ends by suggesting that this emerging technology has the opportunity to revolutionize how we treat neurological diseases and other extremely targeted therapeutic interventions.