How do you send drugs to specific parts of the body so they do their job and avoid causing side effects elsewhere? According to researchers at Stanford University, the answer is a combination of nanoparticles, a pulse of ultrasound, and sugar.
The team has developed a system to deliver drugs anywhere in the body accurate up to a few millimeters. Radiology professor Raag Airan, senior author of the study that appeared in Nature Nanotechnology this week, explained that this could "maximize the therapeutic effect and minimize the off-target effects” of many drugs we use today.
The researchers tested their approach using ultrasound-responsive drug delivery nanoparticles on rats with two drugs. Up first was a dose of ketamine encapsulated in nanoparticles for precise delivery, with a sugar solution (containing 5% sucrose, to be precise) to stabilize the drug.
When it was delivered through an injection and then activated with a pulse of low-intensity ultrasound focused on a particular region of the brain with a special transducer, three times as much ketamine was found in that region than in other parts of the brain, indicating that the drug was precisely released.
The researchers also tested the targeted delivery of ketamine to the rats' prefrontal cortex – which regulates emotional stress – to successfully calm their anxious behavior. That indicates this system might help clinicians treat depression in humans using ketamine in a similar manner, without the dissociative effects this commonly brings on.
The team also used this approach to block pain in the sciatic nerve in one leg of a rat using a local anesthetic. What's cool about this is that it can enable patients to receive injections elsewhere on the body, where it wouldn't be too painful to receive a jab, and then have the anesthetic activate at the site of treatment using focused ultrasound there.
This isn't the first time the use of ultrasound has been explored for drug delivery. We've seen folks at MIT using it to blast off the top layer of skin to enable painless drug delivery back in 2012; researchers at Oxford aimed ultrasound beams at heat-sensitive drug capsules to directly target tumors in 2018; and in 2023, an MIT team's wearable hydrogel patch sent pulses of ultrasound to shoot microjets of fluid drug molecules through skin.
Professor Airan had looked into ultrasound tech for drug delivery too, and had devised a system in 2018 that was less-than-perfect because the drug-laden nanoparticles he was working with weren't stable at body temperature, and would allow the medication to seep out all over the place.
He perfected his system by switching out the shell material for the nanoparticles, and using a sugar solution to ensure their acoustic impedance – which refers to how easily sound waves travel through a material – was different from the medium they were traveling through, so the ultrasound could interact specifically with them.
The team is currently working to set up the first human trial with this system, which will see the use of ketamine to target a patient’s emotional experience of chronic pain. That means that it will be a few years before it receives the necessary approvals for commercialization, but it certainly seems like a promising approach to enabling the use of psychotropic drugs to treat mental health issues while limiting potential side effects.
Source: Stanford University
