An innovative drug-delivery system - nanoparticles encapsulating nitric oxide
or prescription drugs - shows promise for topical treatment of erectile dysfunction
(ED), according to a new study by scientists at Albert
Einstein College of Medicine of Yeshiva University.
 | | Nanoparticles developed by Einstein researchers can ferry drugs or other medically useful substances across the skin. In this study involving rats, nanoparticles contained either nitric oxide (shown above) or nitric oxide plus the drugs sialorphin or tadalafil. When carried across the skin, these agents relaxed smooth muscle tissue, resulting in increased blood flow and erectile activity. Credit: Albert Einstein College of Medicine |
The new system, tested successfully on a small number of animals, could potentially
prevent side effects associated with oral ED medications, if study results can
be replicated in humans. That could mean safer and more effective ED therapy
for millions of men with heart disease and other health problems affecting erectile
function. The study is published today in the online edition of the Journal
of Sexual Medicine.
Tens of millions of men worldwide have benefited from oral ED medications such
as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis). However,
these medications - which belong to a class of drugs called phosphodiesterase
type 5 (PDE5) inhibitors - have limitations. They can cause systemic side effects
that can be serious. These side effects include headache, facial flushing, nasal
congestion, upset stomach, abnormal vision as well as isolated reports of hearing
and vision loss. Men who've recently suffered a heart attack or stroke or have
severe heart disease should use these drugs with caution or not at all. In addition,
"an estimated 30 to 50 percent of men with ED do not respond to oral use
of PDE5 inhibitors," says senior author Kelvin P. Davies, Ph.D., associate
professor of urology at Einstein.
The drug-delivery system, developed by Einstein scientists, consists of nanoparticles
– each smaller than a grain of pollen – that can carry tiny payloads
of various drugs or other medically useful substances and release them in a
controlled and sustained manner.
The limited number of topical formulations of ED drugs has so far proven ineffective.
This study was done to evaluate whether the Einstein nanoparticles, which have
been shown to penetrate the skin, might allow the targeted delivery of compounds
that treat ED and thereby avoid the drugs' systemic effects.
An effective topical therapy could be especially significant for those ED patients
– particularly men with diabetes – who have reduced levels of nitric
oxide (NO), the signaling molecule that dilates blood vessels responsible for
erectile activity. These men, who often aren't helped by oral PDE5 inhibitor
drugs, may benefit from direct application of NO or the PDE5 inhibitors.
The nanoparticles were tested on a total of 18 rats bred to have age-related
ED. The rats were divided into three treatment groups. One group of seven rats
received nanoparticles encapsulating NO. A second group of five rats received
nanoparticles encapsulating NO plus an experimental ED drug called sialorphin
(which has a mechanism of action different from PDE5 inhibitors). A third group
of six received nanoparticles encapsulating NO plus tadalafil (Cialis).
Five of the seven rats treated with the NO-containing nanoparticles, and all
11 rats treated with nanoparticles encapsulating NO plus sialorphin or tadalafil
showed significantly improved erectile function. None of the seven rats in a
control group, which received empty nanoparticles, showed any improvement.
"Most of the animals, nearly 90 percent, showed a response to treatment
with the nanoparticles," says co-author Joel M. Friedman, M.D., Ph.D.,
professor of physiology & biophysics and of medicine. Dr. Friedman developed
the nanoparticles with his son Adam Friedman, M.D., chief resident in the division
of dermatology of the department of medicine at Montefiore Medical Center, The
University Hospital and Academic Medical Center for Einstein.
"The response time to the nanoparticles was very short, just a few minutes,
which is basically what people want in an ED medication," adds Dr. Davies.
"In both rats and humans, it can take 30 minutes to one hour for oral ED
medications to take effect."
Postmortem examination of the tissues at the site of administration showed
no signs of local inflammation or toxicity. "In addition, when we applied
the nanoparticles at therapeutic doses, we found no indication of systemic side
effects," says Dr. Friedman.
The Einstein research team will carry out safety and dosing studies in rats
in the coming months. Clinical studies on humans could begin in a few years
if animal studies continue to show that the nanoparticle delivery system is
safe and effective. But the investigators caution that the time from a proof-of-concept
trial in animals to approved use in humans may be a decade or more.
The paper, "Nanoparticles as a novel delivery vehicle for therapeutics
targeting erectile dysfunction," is published in the September 18, 2009
online edition of the Journal of Sexual Medicine. The lead authors are George
Han, an M.D.-Ph.D. student at Einstein, Moses Tar, M.D., assistant professor
of urology at Einstein, Dwaraka Srinivasa Rao Kuppam, a technician in the Einstein
urology department, Adam Friedman, M.D., of Montefiore Medical Center, and Arnold
Melman, M.D., chairman of urology at Einstein, also contributed to the research.
Albert Einstein College of Medicine of Yeshiva University is one of the nation's
premier centers for research, medical education and clinical investigation.
It is home to 2,775 faculty members, 625 M.D. students, 225 Ph.D. students,
125 students in the combined M.D./Ph.D. program, and 380 postdoctoral research
fellows. In 2008, Einstein received more than $130 million in support from the
NIH. This includes the funding of major research centers at Einstein in diabetes,
cancer, liver disease, and AIDS. Other areas where the College of Medicine is
concentrating its efforts include developmental brain research, neuroscience,
cardiac disease, and initiatives to reduce and eliminate ethnic and racial health
disparities. Through its extensive affiliation network involving eight hospitals
and medical centers in the Bronx, Manhattan and Long Island – which includes
Montefiore Medical Center, The University Hospital and Academic Medical Center
for Einstein – the College of Medicine runs one of the largest post-graduate
medical training programs in the United States, offering approximately 150 residency
programs to more than 2,500 physicians in training. For more information, please
visit www.einstein.yu.edu
Posted September 18th, 2009
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