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| Researchers from the University of North Carolina at Chapel Hill show that exosomes loaded with catalase (shown in red) efficiently interact with neurons (shown in black) to protect them from the effects of Parkinson's disease. |
Pharmaceutical researchers at UNC are
the first to use exosomes -- lipid-and-protein spheres produced by cells -- as
vehicles to deliver a potent large-molecule drug to the brain
UNIVERSITY OF NORTH CAROLINA AT
CHAPEL HILL
May 4,2015
Researchers at the University of
North Carolina at Chapel Hill have used exosomes -- tiny bubbles of protein and
fat produced naturally by cells -- to bypass the body's defenses and deliver a
potent antioxidant directly to the brain to treat Parkinson's disease.
And what's the best way of getting
her drug-packed exosomes to the brain? It looks like a simple nasal spray will
do the trick, say Elena Batrakova and her colleagues at the UNC Eshelman School
of Pharmacy's Center for Nanotechnology in Drug Delivery.
Batrakova and her colleagues
extracted exosomes from immune cells and successfully loaded them with the
enzyme catalase, a potent antioxidant that counters the neuron-killing
inflammation responsible for Parkinson's and other degenerative neurological
disorders. Their work was published in the Journal of Controlled Release.
This is the first time a large
therapeutic protein like catalase has been delivered to the brain using
exosomes. Getting drugs into the brain is extremely difficult in general
because it is protected and isolated from the rest of the body by the
blood-brain barrier, which is extremely selective about what is allowed to pass
through.
Batrakova and her team at the
pharmacy school harvested exosomes from macrophages, white blood cells that are
responsible for clearing foreign material from the body. Exosomes are tiny
spheres produced by cells to carry chemical messages. They are made of the same
material that makes up cell membranes. Diseases like cancer and AIDS propagate
throughout the body by hijacking exosomes.
"Exosomes are engineered by
nature to be the perfect delivery vehicles for proteins and genetic
material," Batrakova says. "Catalase is a huge protein, and it is
almost impossible to deliver across the blood-brain barrier alone. We use
exosomes from white blood cells, which are invisible to the immune system and
easily interact and fuse with the blood-brain barrier to deliver their cargo
across it."
Catalase counteracts the effects of
free radicals, destructive molecules that are byproducts of cellular activity
and especially prevalent in areas of chronic inflammation.
"Catalase is one of the most
potent antioxidants in nature," Batrakova says. "One molecule of
catalase can deactivate about one million free radicals per second, and it
never stops because the enzyme is not consumed in the reaction. No small
molecule drug even comes close to matching it in speed or efficiency."
Traditional drugs -- from cold
medicine to chemotherapy -- are composed of small molecules of a few dozen
atoms, typically. Biopharmaceuticals, or biologics, are proteins produced by
living cells. Proteins such as catalase are tens of thousands of times larger
than the small molecules that make up traditional drugs.
Batrakova's goal is to develop
personalized treatments by loading proteins into exosomes that have been
extracted from a patient's own white blood cells. These packages of medicine
will be ignored by the patient's immune system, which works against unknown
proteins as well as many synthetic delivery vehicles.
http://health.einnews.com/article/263566177/QSll28fQ7tLpxAqB
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