BGU scientists overcome ‘blood brain barrier’ (JERUSALEM POST) By JUDY SIEGEL-ITZKOVICH 07/31/12)
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After eight years of intensive work, a team of Ben-Gurion University
scientists has overcome the “blood brain barrier” that prevents drugs
from passing into the brain and reaching specific targets to fight
The system of synthetic nanoscale structures, called V-Smart drug
delivery technology, also allows oral medications to pass through the
epithelial tissue of the intestinal wall and other biological
membranes; thus, the Beersheba researchers hope that injectable-only
drugs for a variety of diseases could eventually be made in pill form.
The breakthrough technology, which uses microscopic, bubble-like
membranous structures known as vesicles, was developed by the
interdisciplinary team of emeritus Prof. Eli Heldman of the
university’s clinical biochemistry department, Dr. Sarina Grinberg of
the chemistry department and Dr. Charles Linder of the Avram and
Stella Goldstein- Goren Department of Biotechnology Engineering.
A New York biotech company, Laurel Sciences, has signed a licensing
agreement with BGU’s technology transfer company BGN Technologies.
Articles on the technology have been published by the Negev-based
team in the Journal of Controlled Release, the Journal of Chemistry
and Physics of Lipids and the Journal of Liposome Research, among
Despite great advances in therapeutic drugs, the problem of unwanted
side effects remains a serious obstacle to treating patients. Most
adverse effects are the result of a drug’s interaction with locations
in the patient’s body that are not relevant to its medicinal action.
But if an effective delivery system can make medications more
available at target locations, the amount of harmful side effects is
The V-Smart delivery system could be especially relevant to diseases
of the central nervous system, from Parkinson’s and Alzheimer’s to
multiple sclerosis, amyotropic lateral sclerosis and neurological
complications of HIV, as well as brain cancers.
The scientists administered V-Smart vesicles intravenously and orally
to lab mice to deliver to the brain encapsulated material such as
analgesic peptides that greatly reduced pain.
In an interview on Sunday with The Jerusalem Post, Heldman predicted
that the technology could be used in clinical trials in about two
The technology is based on nano-sized vesicles formed from a
combination of specifically designed structures called
The tiny sacs, which are somewhat like fat globules called liposomes,
but synthetic, are highly stable and provide a controlledrelease
mechanism that makes it possible for drugs to pass through biological
barriers. It then pinpoints exactly where the drug will be released
in the brain, thus making the drugs more efficient and reducing side
The blood brain barrier was meant by the body to keep poisons out of
the brain by separating circulating blood from the brain’s
extracellular fluid in the central nervous system. It occurs along
all capillaries and consists of tight junctions around the
capillaries that do not exist in normal circulation.
But it also bars the entry of many beneficial drugs. Thus, using
nanoparticles to deliver medications across this divide is very
The work on oral medication delivery is preliminary but very
promising, Heldman said. Teams working elsewhere have found other
methods, including the injection of hyperosmotic solutions that
shrink cells or the injection of drugs into the brain.
“But our system is much better because it doesn’t break the blood
brain barrier,” he explained. “It also has great stability, can
target where the drug will be sent and releases the encapsulated
drugs in a controlled manner at the target site.”
“Archi-bacteria, which are organisms that live under very extreme
conditions, such as in volcanoes, triggered our ideas for the
technology,” Heldman said. “To survive, they evolved lipids that gave
them stability over a long period. But these lipids have to be very
pure and it’s very difficult to synthesize them.”
He added that the team chose to create bola lipids, “which are like
two-headed weapons and have a different kind of membrane. The result
is a very stable and selective mechanism that makes it possible to
release drugs in the spot we want beyond the blood brain barrier.”
The BGU scientist said the team was also working on a delivery system
for use in specific parts of the brain for Parkinson’s disease.
“So far, the delivery system has been shown to work,” he said. “But
it still needs a lot of development. I estimate that in six months we
can persuasively prove that the system works.”
Heldman recently returned from the US National Institutes of Health,
where he worked for three years on “small-interference RNA”
to “silence” genes for the delivery of nucleic acids into the brain
that he and his BGU team had first developed in Beersheba.
“Our patented technique could have major therapeutic potential for
treating disease,” he said.
Heldman also said that BGU and Lauren Sciences, where he is chief
scientific officer, had recently been awarded two prestigious
research grants, one from the Michael J. Fox Foundation to develop
the delivery of proteins in the treatment of Parkinson’s disease, the
other from the Campbell Foundation for delivery of the antiretroviral
drug Tenofovir for treatment of neuro- HIV.
“We hope that the success of these projects will improve these
patients’ lives,” he said.
Prof. Shlomo Constantini, head of pediatric neurosurgery at the Dana
Hospital of Tel Aviv Sourasky Medical Center, was impressed when he
heard of the BGU development.
“This is exciting, fascinating and has huge potential,” Constantini
said. (© 1995-2011, The Jerusalem Post 07/31/12)
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