New Topical Gel Effective in Healing Chronic Wounds

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 Dermatology. The research team seeks approval from the US Food and Drug Administration (FDA) to use the topical gel for chronic wounds.

"The FDA 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."

Chronic wounds 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 with diabetes.

Drugs for Hypertension as a Treatment for Chronic Wounds

Angiotensin II 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 Losartan

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 phase

Group 2 treatment started on day seven after wound infliction to target the proliferative phase of tissue healing

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Group 3 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 rate.

Topical Application of Valsartan

The research 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.

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The findings showed that valsartan was more effective in accelerating wound healing than losartan. 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.

The research 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 entire body.

Oral ingestion 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 bloodstream.

The research 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.

"Our 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.

"Now that 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.

Reference:

1. 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

Source-Medindia