Tiny Doses of Drugs Delivered Directly to the Brain Using Ultrathin Needles

Tiny Doses of Drugs Delivered Directly to the Brain Using Ultrathin Needles

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Highlights:
  • Ultrathin needles, as thin as human hair can now be used to deliver small quantities of medicine directly to the brain.
  • Directly targeting specific regions of the brain can treat the precise neural circuits without interfering with normal body function.
  • The extremely small cannula allows the delivery of drugs to only about a cubic millimeter of the brain, limiting exposure of the drug to unspecific brain regions.
Using an ultrathin needle as thin as the human hair, a research team at MIT has been able to deliver tiny quantities of medication directly into brain regions as small as 1 cubic millimeter. This allows targeting very specific areas deep inside the brain with precise control without letting the drugs enter the central nervous system or interfere with normal body functions. The study was published in the journal Science Translational Medicine.

A miniaturized system

The device contains several tubes encapsulated within a needle. Using microfabrication techniques, the tubes were developed to measure about 30 micrometers in diameter and up to 10 centimeters in length. The tubes are contained in a stainless steel needle with a diameter of about 150 microns. The tubes may contain one or more drugs that can be directed towards specific regions in the brain with precise control of how much of the drug is given and where it goes. In an experiment on rats, the team was successfully able to deliver targeted doses of a drug that affects the animals' motor function.
Tiny Doses of Drugs Delivered Directly to the Brain Using Ultrathin Needles

"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," says Canan Dagdeviren, the lead author of the paper.

The problem with central nervous system drugs

Drugs used to treat brain disorders are generally orally taken and act on the central nervous system. These drugs interact with neurotransmitters in the brain, sometimes causing undesired effects on undesired brain regions. For example, while l-dopa, a dopamine precursor used to treat Parkinson's disease function by boosting serotonin levels in patients with depression, it can have side effects because it acts throughout the brain.

"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. 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," Michael Cima, co-author of the study says.

The mice trial

In an experiment in mice, the team delivered a drug called muscimol to the substantia nigra, a brain region located deep within the brain that helps control movement. The cannulas were connected to small pumps that could be implanted under the skin. Using these pumps tiny doses of over hundreds of nanoliters could be delivered into the brains of rats.

Muscimol induces symptoms similar to those seen in Parkinson's disease. When the drug was delivered with the miniaturized delivery needle to the rat brain, the team was able to generate Parkinson's symptoms including stimulating the rats to continually turn in a clockwise direction. They were also able to halt the Parkinsonian behavior by delivering a dose of saline through a different channel, to wash the drug away.

"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," Dagdeviren says.

The study reports that the cannulas can be fabricated in nearly any length and thickness, which makes it possible to create the right size for the different brain regions they target. The success in rats could one day translate into human brains.

Reference:
  1. C. Dagdeviren el al., "Miniaturized neural system for chronic, local intracerebral drug delivery," Science Translational Medicine (2018), DOI: 10.1126/scitranslmed.aan2742
Source: Medindia
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