While drugs are developed to target a specific region in the body, most oral drugs have systemic effects which can range from mild adverse events to more serious toxicities. Drug development for neurological disorders becomes even more complex as the blood-brain barrier prevents most systemically-administered therapies from passing into the brain space.
Now, researchers at MIT have developed a miniaturized neural drug delivery system capable of microdosing specific regions of the brain. As the device is capable of isolating brain regions down to one cubic millimeter, it could allow for targeted dosing of therapies without having any negative effects on the rest of the brain.
“We believe this tiny microfabricated device could have tremendous impact in understanding brain diseases, as well as providing new ways of delivering biopharmaceuticals and performing biosensing in the brain,” said Robert Langer, the David H. Koch Institute Professor at MIT.
According to the researchers, the needle-like device is around the width of a human hair, and contains multiple smaller tubes which can deliver one or more drugs to a specific region within the brain. When they tested the drug delivery device on rats, the researchers found they were able to precisely alter the animals’ motor function by targeted delivery of a drug.
“We can infuse very small amounts of multiple drugs compared to what we can do intravenously or orally, and also manipulate behavioral changes through drug infusion,” said lead author Canan Dagdeviren, the LG Electronics Career Development Assistant Professor of Media Arts and Sciences at MIT. Dagdeviren and his colleagues published their findings in the journal Science Translational Medicine.
Medications used to treat neural disorders like Parkinson’s disease and depression often affect neurotransmitters throughout the brain, Because the effects of these drugs is not localized, patients often experience treatment-related side effects.
“One of the problems with central nervous system drugs is that they’re not specific, and if you’re taking them orally they go everywhere,” said Michael Cima, the David H. Koch Professor of Engineering in the Department of Materials Science and Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research. “The only way we can limit the exposure is to just deliver to a cubic millimeter of the brain, and in order to do that, you have to have extremely small cannulas.”
Cannulas are tubes used to deliver fluids to areas in the body, so the researchers used microfabrication techniques to make tubes that were around 30 micrometers in diameter and enclosed within a stainless steel needle. Small, implantable pumps were then connected to the miniaturised cannulas to allow for targeted dosing of very small drug volumes.
“The device is very stable and robust, and you can place it anywhere that you are interested,” said Dagdeviren. “Since the device can be customizable, in the future we can have different channels for different chemicals, or for light, to target tumors or neurological disorders such as Parkinson’s disease or Alzheimer’s.”
The device is still in the early stages of development, however the researchers keep coming up with ways that the miniaturized drug delivery device could benefit patients.
“Even if scientists and clinicians can identify a therapeutic molecule to treat neural disorders, there remains the formidable problem of how to delivery the therapy to the right cells – those most affected in the disorder,” said Ann Graybiel, an MIT Institute Professor and a member of MIT’s McGovern Institute for Brain Research. “Because the brain is so structurally complex, new accurate ways to deliver drugs or related therapeutic agents locally are urgently needed.”