Global Statistics

All countries
194,789,654
Confirmed
Updated on July 26, 2021 12:06 am
All countries
175,022,400
Recovered
Updated on July 26, 2021 12:06 am
All countries
4,174,480
Deaths
Updated on July 26, 2021 12:06 am

Global Statistics

All countries
194,789,654
Confirmed
Updated on July 26, 2021 12:06 am
All countries
175,022,400
Recovered
Updated on July 26, 2021 12:06 am
All countries
4,174,480
Deaths
Updated on July 26, 2021 12:06 am

Novel neurotransmitters effectively cross the blood-brain barrier

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Researchers have found a seemingly safe way to administer drugs directly into the brain: through a previously unknown type of neurotransmitters. They tested this approach in mice.

neurotransmitters in the brainShare on Pinterest
A previously unknown type of neurotransmitters (chemical messengers) may provide a safe method of getting medication across the blood-brain barrier.

The blood-brain barrier poses a crucial challenge for doctors hoping to deliver drugs and other therapeutic substances directly to the brain.

A new study from researchers at Tufts University in Boston, MA, describes a way of getting medication safely across the blood-brain barrier.

The researchers found that certain neurotransmitters can help lipid-based nanoparticles pass through the blood-brain barrier and into the brain.

Corresponding author, Tufts biomedical engineer Qiaobing Xu says that:

“We can deliver a wide range of molecules by packaging them into the lipid-based nanoparticles without chemically modifying the drugs themselves. We can also achieve delivery across the blood-brain barrier without disrupting the integrity of the barrier.”

The study appears in Science Advances.

The blood-brain barrier consists of a blood vessel lining of endothelial cells that keeps foreign molecules from escaping from the blood vessels and entering the brain fluid where they could affect neurons and other brain cells. The barrier is highly selective about the non-native molecules it allows into the brain, and that includes therapeutic substances.

While small molecule or macromolecule drugs have the potential to treat brain tumors, infections, neurogenerative disorders, and stroke, the presence of the blood-brain barrier makes it difficult for doctors to administer such therapies.

Scientists have attempted various workarounds, and none have proven sufficiently safe or effective. Direct injection of compounds into the brain, as well as efforts to force ‘leaks’ through the barrier, carry risks, such as neurotoxicity, infection, and tissue damage.

Researchers have looked into the use of “carriers,” such as monoclonal antibodies and modified viruses, that travel into the brain, taking therapeutic molecules with them.

However, cost and safety concerns accompany this approach. Scientists have also investigated a similar use of polymers, nanocapsules, and nanoparticles with some success. However, adapting these materials for such use is often complicated.

However, the blood-brain barrier does allow certain neurotransmitters into the brain. Xu and his colleagues have developed a system that uses a particular class of neurotransmitters as a means to traverse the barrier, carrying molecules into the brains of mice.

The authors of the study began by attaching one of these neurotransmitters to fat-, or lipid-like molecules. Next, they doped these combined neurotransmitter-lipidoids, or NT-lipidoids, into lipid-nanoparticles (LNPs).

LNPs are small lipid bubbles into which the scientists inserted therapeutic molecules. The scientists can inject the NT-lipidoid LNPs and the molecules they contain into the bloodstream intravenously.

When the LNPs arrive at the blood-brain barrier, their neurotransmitter provides entry, delivering the molecules they carry directly and safely to the brain’s neurons and other cells.

Co-author Feihe Ma notes that “It’s simple, effective, and potentially broadly applicable — we can modify the container for the drug, and by adding the NT-lipidoid, it’s like attaching an address label for delivery into the brain.”

Researchers from the Xu laboratory report the successful delivery of the following NT-lipidoid LNPs:

  • amphotericin B, a small-molecule antifungal drug
  • a tau antisense oligonucleotide that inhibits the production of the tau proteins associated with Alzheimer’s disease
  • GFP-Cre, a gene-editing protein.

The team was able to confirm the successful targeting of these payloads to the mice’s brains. In the case of the tau antisense oligonucleotide, they observed a reduction in tau proteins.

The GFP-Cre protein was the first-ever instance of genome editing of neuronal cells initiated intravenously.

In addition to the substances tested for the study, Xu expects that scientists can use the LNPs to deliver a variety of therapeutic substances to the brain, including DNA and large-enzyme complexes.

“The power of our method is that it is extremely versatile and relatively non-disruptive,” says Xu.

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