Professor Yechezkel “Chezy” Barenholz
The PhysOrg article Overcoming Drug Resistance — Nanoparticles Trigger Built-In Cell-Death Signal said
One of the most vexing problems in treating cancer is the propensity of tumors to develop resistance to a wide range of anticancer drugs. Over 70 percent of ovarian cancer patients, for example, have drug-resistant tumors at the time of their initial diagnosis, and virtually all patients who relapse have drug-resistant tumors.
Researchers have identified the major mechanisms that cancer cells use to neutralize the cytotoxic, or cell-killing, effects of anticancer drugs, and now they are using nanotechnology to help derail drug resistance and improve the odds of successfully treating cancer.
Yechezkel Barenholz, Ph.D., and his collaborators at the Hebrew University-Hadassah Medical School in Jerusalem added a lipid-polymer construct to liposomes intended to encapsulate ceramide. The resulting nanoparticles were far more stable than standard liposomes. As a result, these liposomes were able to deliver larger doses of ceramide to tumor cells, increasing the therapeutic efficacy of ceramide administration. The resulting liposomes were also more stable when stored, a useful characteristic should such a formulation eventually receive regulatory clearance for use in humans.
Yechezkel “Chezy” Barenholz, Ph.D. is Professor of Biochemistry and
head of the Department of Biochemistry at the
Hebrew University of Jerusalem. He is on the Editorial Boards of
Chemistry and Physics of Lipids and the
Journal of Liposome Research.
He is one of the key inventors of
DOXIL, marketed by Johnson & Johnson
as a
cancer treatment.
In basic research, he focuses on
biochemistry and biophysics of lipids and membranes — on the
relationships between membrane lipid composition, structure (e.g.,
rafts), and function; on lipid mediated signal transduction; and on
apoptosis. One of the main biological topics studied is the relevance of
the above to aging processes.
In applied research, Chezy’s main interests are in
amphiphile-based drug carriers, especially liposomes: from basic aspects
of design of the drug carriers through animal studies and clinical
trials, and finally, FDA-approved drugs. This is best exemplified by the
development of DOXIL (a doxorubicin remote-loaded sterically-stabilized
~100 nm liposome for treatment of cancer).
Among his 300+ publications, Chezy coedited
Handbook of Nonmedical Applications of Liposomes,
and coauthored
Dynamics of the Hydrocarbon Layer in Liposomes of Lecithin
and Sphingomyelin Containing Dicetylphosphate,
Pharmacokinetics of Pegylated Liposomal Doxorubicin: Review of Animal
and
Human Studies,
Electrostatic and structural properties of complexes involving
plasmid
DNA and cationic lipids commonly used for gene delivery,
Prolongation of the Circulation Time of Doxorubicin Encapsulated in
Liposomes Containing a Polyethylene Glycol-Derivatized Phospholipid:
Pharmacokinetic Studies in Rodents and Dogs, and
Electrostatic parameters of cationic liposomes commonly used for gene
delivery as determined by 4-heptadecyl-7-hydroxycoumarin.
His 30+ patents include
Sphingolipids’ Polyalkylamines Conjugates,
Liposomal analgesic drug compositions prepared in GMV using an ammonium
sulfate gradient,
Liposomal Formulations Comprising an Amphipathic Weak Base Like
Tempamine for Treatment of Neurodegenerative Conditions,
Liposomal Compositions of Glucocorticoid and Glucocorticoid
Derivatives,
Combination Therapy,
Use of Liposomal Glucocorticoids for Treating Inflammatory States,
Method for Selecting Cationic or Anionic Liposomes for Treatment of a
Mucosa Membrane, and Kit Comprising the Same,
Enhanced circulation effector composition and method, and
Platinum complexes and their use in therapy.
Chezy earned his undergraduate, M.Sc., and Ph.D. degrees in
Biochemistry from the Hebrew University, Jerusalem in 1965, 1968, and
1971, respectively.