- Drugs to treat hypertension may be
used to develop a topical gel to accelerate healing of chronic wounds
- Topical gel made from a drug
called valsartan was effective in treating chronic wounds
- The gel can be used to treat
wounds among older adults and those with diabetic foot ulcers
A topical gel
made from blood pressure drugs can block inflammation pathways and accelerate
wound healing, according to a study conducted by an international research team
led by Johns Hopkins. The topical gel can be used to treat skin wounds among
older adults and people with diabetes
The findings of
the study are published in the Journal of Investigative
The research team seeks approval from the US Food and
Drug Administration (FDA) to use the topical gel for chronic wounds.
‘A topical gel made from drugs to treat hypertension may have positive biological effects that facilitate and accelerates chronic wound healing.’
has not issued any new drug approval for wound healing in the past ten
years," says Peter Abadir, M.D., associate professor of medicine at the
Johns Hopkins University School of Medicine and the paper's first author.
"Using medicines that have been available for more than two decades, we think
we have shown that this class of medicines holds great promise in effectively
healing chronic wounds that are prevalent in diabetic and aged patients."
are skin injuries that fail to heal and increase the risk of infection and
tissue breakdown. In 2008, chronic wounds accounted for more than 100 million
hospital visits in the United States, said Abadir.
In the recent
years, scientists have turned their attention to the skin's renin-angiotensin
system (RAS) in wound healing. RAS is involved in the skin's inflammatory
response, collagen deposition, and signaling necessary for wound healing.
Studies have shown that RAS is abnormally regulated in older adults and those
Drugs for Hypertension as a Treatment for Chronic
receptor antagonists or blockers are a class of drugs that includes losartan
- and valsartan,
commonly prescribed drugs for high blood pressure
. The drugs block RAS and
increase wound blood flow. Abadir and team experimented with gel formulations
from these oral drugs. The goal was to apply the gels directly to wounds to
increase wound tissue levels of the drugs that promote faster healing.
Topical Application of
The research team
conducted an experimental study in mice. They tested 5 percent of topical
losartan on mice in three different phases of wound healing.
Group 1 received
treatment for upto three days post-wound infliction to target the inflammatory
Group 2 treatment
started on day seven after wound infliction to target the proliferative phase
of tissue healing
treatment started the first day of wound infliction until closure to treat all
wound healing phases
The fourth group
was the control which was given standard care and a placebo. The findings
showed that mice in group 2 experienced the most accelerated wound healing
Topical Application of
team also compared the effects of different concentrations of losartan and valsartan
on young and old diabetic mice during the proliferation phase of wound healing,
which involves the regrowth of normal tissue.
showed that valsartan was more effective in accelerating wound healing than
One percent of valsartan had the greatest impact on total closure
compared to other drugs. Ten percent of losartan led to the worst wound
healing, which is attributed to toxicity.
Half of all mice
that received one percent valsartan achieved complete wound healing. However,
only 10 percent of the mice given the placebo did.
team tested the effect of one percent valsartan on wounds among aged, diabetic
pigs. One percent valsartan healed the wounds much more quickly when compared
with pigs in the placebo group. The wounds were closed by day 50 compared with
none of the placebo-treated wounds. This finding suggests that valsartan
acts locally on the tissues where it's absorbed, rather than affecting the
of valsartan yields 4,000 to 5,000 nanomoles in the blood level for a human.
Thus, topical application of valsartan will not be absorbed into the
team examined the collagen content and tensile strength in the pig's skin to
determine the biological effects of one percent valsartan on wound healing.
Pigs treated with valsartan had a thicker epidermal and dermal layer. The
arrangement of collagen fiber was more organized, indicating that topical
application of one percent valsartan leads to stronger healing of the skin.
strategy for specifically targeting the biology that underlies chronic wounds
in diabetics and older adults differs greatly from other approaches to wound
care thus far. The topical gel likely enables a cascade of positive biological
effects that facilitates and accelerates chronic wound healing," said Dr
Jeremy Walston, Professor of Medicine and the paper's senior author.
we've proven efficacy in animals, we're moving on to the next stage of
FDA-required testing in humans. Hopefully, this medication will be available
for public use in a few years, if further research bears out our results,"
adds Walston. The team hopes that the medication could one day also be used
to treat scars, wrinkles and other skin problems.
- Peter Abadir, Sayed Hosseini, Mahya Faghih, Amir Ansari, Frank Lay, Barbara Smith, Aleksandra Beselman, Diep Vuong, Alan Berger, Jing Tian, David Rini, Kevin Keenahan, Joshua Budman, Tadashi Inagami, Neal Fedarko, Guy Marti, John Harmon, Jeremy Walston. Topical Reformulation of Valsartan for Treatment of Chronic Diabetic Wounds. Journal of Investigative Dermatology, (2017) DOI: 10.1016/j.jid.2017.09.030