Miniaturised neural system developed for chronic local intracerebral drug delivery

Researchers have devised a miniaturised system that can deliver tiny quantities of medicine to brain regions as small as 1 cubic millimetre. This type of targeted dosing could make it possible to treat diseases that affect very specific brain circuits, without interfering with the normal function of the rest of the brain, the researchers say.

The MIT team set out to develop a miniaturised cannula that could target very small areas. Using microfabrication techniques, the researchers constructed tubes with diameters of about 30 micrometres and lengths up to 10 centimetres. These tubes are contained within a stainless steel needle with a diameter of about 150 microns. "The device is very stable and robust, and you can place it anywhere that you are interested," says Canan Dagdeviren, the LG Electronics Career Development Assistant Professor of Media Arts and Sciences.

The researchers connected the cannulas to small pumps that can be implanted under the skin. Using these pumps, the researchers showed that they could deliver tiny doses (hundreds of nanoliters) into the brains of rats. In one experiment, they delivered a drug called muscimol to a brain region called the substantia nigra, which is located deep within the brain and helps to control movement.

Even if scientists and clinicians can identify a therapeutic molecule to treat neural disorders, there remains the formidable problem of how to deliver the therapy to the right cells

Previous studies have shown that muscimol induces symptoms similar to those seen in Parkinson’s disease. The researchers were able to generate those effects, which include stimulating the rats to continually turn in a clockwise direction, using their miniaturised delivery needle. They also showed that they could halt the Parkinsonian behaviour by delivering a dose of saline through a different channel, to wash the drug away.

"Since the device can be customisable, in the future we can have different channels for different chemicals, or for light, to target tumours or neurological disorders such as Parkinson’s disease or Alzheimer’s," Prof Dagdeviren says.

This device could also make it easier to deliver potential new treatments for behavioural neurological disorders such as addiction or obsessive-compulsive disorder, which may be caused by specific disruptions in how different parts of the brain communicate with each other.

"Even if scientists and clinicians can identify a therapeutic molecule to treat neural disorders, there remains the formidable problem of how to deliver the therapy to the right cells — those most affected in the disorder. Because the brain is so structurally complex, new accurate ways to deliver drugs or related therapeutic agents locally are urgently needed," says Ann Graybiel, an MIT Institute Professor and a member of MIT’s McGovern Institute for Brain Research, who is also an author of the paper.

The researchers also showed that they could incorporate an electrode into the tip of the cannula, which can be used to monitor how neurons’ electrical activity changes after drug treatment. They are now working on adapting the device so it can also be used to measure chemical or mechanical changes that occur in the brain following drug treatment.

The cannulas can be fabricated in nearly any length or thickness, making it possible to adapt them for use in brains of different sizes, including the human brain, the researchers say.

Using this device, which consists of several tubes contained within a needle about as thin as a human hair, the researchers can deliver one or more drugs deep within the brain, with very precise control over how much drug is given and where it goes. In a study of rats, they found that they could deliver targeted doses of a drug that affects the animals’ motor function.

"We can infuse very small amounts of multiple drugs compared to what we can do intravenously or orally, and also manipulate behavioural changes through drug infusion," says Prof Dagdeviren.

"We believe this tiny microfabricated device could have a tremendous impact in understanding brain diseases, as well as providing new ways of delivering biopharmaceuticals and performing biosensing in the brain," says Robert Langer, the David H. Koch Institute Professor at MIT and one of the paper’s senior authors.

The research has been published in Science Translational Medicine.