Key Points
- Researchers at Stanford University were successful in encapsulating drugs for neurological applications in acoustically activatable liposomes.
- When exposed to low-intensity focused ultrasound, the drugs were released from the liposomes with site-specific delivery.
Source: Purohit, M.P., Yu, B.J., Roy, K.S. et al. Acoustically activatable liposomes as a translational nanotechnology for site-targeted drug delivery and noninvasive neuromodulation. Nat. Nanotechnol. (2025). https://doi.org/10.1038/s41565-025-01990-5
Delivering a specific drug to the right place at the right time is critical in the treatment of many diseases and disorders. Ultrasound can provide a targeted, focused stimulus for the release a specific drug from a nanocarrier to millimeter-sized areas of the brain and bodily regions of interest. Specific targeting also decreases unwanted side effects.
The research team at Stanford University led by Raag Airan, MD, PhD, assistant professor of neuroradiology, published its recent preclinical work developing acoustically activable liposomes (AALs) for drug delivery in neuromodulation applications. Liposomes are nanoparticles that have a lipid bilayer shell and can be loaded with different drugs or therapeutics. In addition, liposomes can be synthesized to release their payload when exposed to ultrasound.
In the published study, the group outlined its new design scheme for AALs as ultrasound-responsive drug delivery vehicles. Importantly, the new AAL formulation is made with common and validated pharmaceutical ingredients, making them safer and more easily used in human clinical trials. The AALs can also be adjusted to increase the interactions with the applied ultrasound.
During testing, the team successfully loaded four different drugs into an AAL and then controllably released the payloads with focused ultrasound. For example, they delivered ketamine to specific brain regions and local anesthetics to the sciatic nerve in the leg. In the brain, the nanoparticles delivered a three-fold increase in the amount of drug when compared with other methods and selectively activated the affective actions of ketamine over its varied other functions.
“Our new ultrasound-responsive drug delivery vehicle is eminently translatable,” said Dr. Airan. “The progress toward clinical translation was made much more rapid when we shifted to the new design.” Dr. Airan’s previous design held less drug and required a complex production, storage, and handling process. The secret sauce in the new formulation turned out to be a 5% sucrose solution (sugar!).
The group looks forward to next steps, where plans include opening a first-in-human clinical trial to target ketamine delivery to the anterior cingulate region of the brain in patients with chronic pain. That trial is slated to open early next year.
The study was funded by the National Institutes of Health BRAIN and HEAL Initiatives, the Stanford Wu Tsai Neurosciences Institute, an anonymous donor to the Stanford Medicine Department of Radiology, the Ford Foundation, and the National Science Foundation. The Focused Ultrasound Foundation provided initial funding that contributed to the local anesthetic work done in the study.
See Nature Nanotechnology (Open Source)
See Stanford University’s Press Release
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