Focused Ultrasound—Enhanced Drug Delivery Using The Glymphatic System

Published: 14 September 2022

Key Points

Researchers recently published the results from a preclinical study on focused ultrasound–enhanced intrathecal drug delivery to the brain.
Intrathecal transfer uses the glymphatic system – which is responsible for clearing waste using perivascular channels.
The focused ultrasound protocol was successful, safe, and significantly effective for increasing the uptake of small molecules in the brain.

The focused ultrasound enabled a greater transfer of molecules from the CSF to the brain tissue compared to the control arm, as illustrated above by a contrast agent.

Image source: Muna Aryal, Matine M. Azadian, Alex R. Hart, Nicholas Macedo, Quan Zhou, Eben L. Rosenthal, Raag D. Airan. Noninvasive ultrasonic induction of cerebrospinal fluid flow enhances intrathecal drug delivery. Journal of Controlled Release. Volume 349,
2022.

Noninvasive Ultrasonic Induction of Cerebrospinal Fluid Flow Enhances Intrathecal Drug Delivery

A research team based at Stanford University and Loyola University Chicago recently published the results from a preclinical study on focused ultrasound–enhanced intrathecal drug delivery to the brain. Intrathecal transfer uses the glymphatic system (a waste clearance system that uses a unique system of perivascular channels) to transfer molecules between the cerebrospinal fluid (CSF) and brain tissue.

The investigators designed and conducted several focused ultrasound experiments to improve drug uptake from CSF to the brain, a process that has traditionally been ineffective. The low-intensity transcranial protocol was tested preclinically with both small and large molecular agents. It was successful, safe, and effective for significantly increasing the uptake of large molecules and biologics. The team was able to move both large and small molecules from the CSF into the perivascular space, as confirmed by MRI and histological analysis.

Beyond drug delivery, the authors concluded that the technique may also be useful for investigating the glymphatic system’s role in other disease processes.

See the Journal of Controlled Release >