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 disease.
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
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
A New York biotech company, Lauren Sciences, has signed a
licensing agreement with BGU’s technology transfer company BGN
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 much reduced.
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
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
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.”
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
The BGU scientist said the team was also working on a
delivery system for use in specific parts of the brain for Parkinson’s
“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
“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.
exciting, fascinating and has huge potential,” Constantini said.
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