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Toxicity reduces if drugs are delivered as liquid salt through skin

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New York: Researchers say that formulating drugs as liquid salts may provide a safe and efficient strategy for topical delivery of drugs that cause skin toxicity. The researchers who brought out the findings also included one of Indian-origin.

A novel formulation of the drug propranolol as a liquid salt enables delivery through the skin with reduced toxicity, the findings showed.

“Propranolol is positively charged which is a likely source of its toxicity. Shielding of this charge by association with a counter species in the liquid salt reduces its toxicity. These findings are broadly applicable to many charged drugs” said study senior author Samir Mitragotri, a professor at the University of California, Santa Barbara in the US.

Skin toxicity remains a major challenge in the design and use of new topical drug formulations. Many drugs must be dissolved in organic solvents which are typically toxic to the skin.

Many drugs such as propranolol itself show dose-dependent skin toxicity. Formulating drugs as liquid salt mitigates both sources of toxicity.

Given their fluid nature, liquid salts eliminate the necessity of organic solvents. In addition, counter ions used to form the liquid salts shield the drug charge, which further reduces drug-induced toxicity.

The researchers said that this is the first study that reports the design of liquid salts to minimise skin toxicity. Such formulations can increase the spectrum of drugs that can be safely delivered via a transdermal patch.

“This technology presents an exciting new, patient compliant solution for treating diseases,” study co-author Michael Zakrewsky from University of California, Santa Barbara. (IANS), (image courtesy: irp-cdn.multiscreensite.com)

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Two of Four Experimental Ebola Drugs Tests in Congo Saving Lives

The preliminary findings prompted an early halt to a major study on the drugs and a decision to prioritize their use in the African country

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Ebola, Drugs, Congo
FILE - Health workers wearing protective gear check on a patient isolated in a plastic cube at an Ebola treatment center in Beni, Congo, July 13, 2019. VOA

Two of four experimental Ebola drugs being tested in Congo seem to be saving lives, international health authorities announced Monday.

The preliminary findings prompted an early halt to a major study on the drugs and a decision to prioritize their use in the African country, where a yearlong outbreak has killed more than 1,800 people.

The early results mark “some very good news,” said Dr. Anthony Fauci of the U.S. National Institutes of Health, which helped fund the study. With these drugs, “we may be able to improve the survival of people with Ebola.”

The two drugs — one developed by Regeneron Pharmaceuticals and the other by NIH researchers — are antibodies that work by blocking the virus.

Ebola, Drugs, Congo
FILE – A man receives a vaccine against Ebola from a nurse outside the Afia Himbi Health Center in Goma, July 15, 2019. VOA

While research shows there is an effective albeit experimental vaccine against Ebola — one now being used in Congo — no studies have signaled which of several potential treatments were best to try once people became sick. During the West Africa Ebola epidemic several years ago, studies showed a hint that another antibody mixture named ZMapp worked, but not clear proof.

So with the current outbreak in Congo, researchers compared ZMapp to three other drugs — Regeneron’s compound, the NIH’s called mAb114 and an antiviral drug named remdesivir.

On Friday, independent study monitors reviewed how the first several hundred patients in the Congo study were faring — and found enough difference to call an early halt to the trial. The panel determined that the Regeneron compound clearly was working better than the rest, and the NIH antibody wasn’t far behind, Fauci explained. Next, researchers will do further study to nail down how well those two compounds work.

The data is preliminary, Fauci stressed. But in the study, significantly fewer people died among those given the Regeneron drug or the NIH’s — about 30% compared to half who received ZMapp. More striking, when patients sought care early — before too much virus was in their bloodstream — mortality was just 6% with the Regeneron drug and 11% with the NIH compound, compared to about 24% for ZMapp, he said.

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Among people who receive no care in the current outbreak, about three-fourths die, said Dr. Michael Ryan of the World Health Organization. All of Congo’s Ebola treatment units have access to the two drugs, he added, saying he was hopeful that the news would persuade more patients to seek care — as soon as symptoms appear.

Quick care ‘vital’

Tackling Congo’s outbreak has been complicated both by conflict in the region and because many people don’t believe Ebola is real and choose to stay at home when they’re sick, which spurs spread of the virus.

“Getting people into care more quickly is absolutely vital,” Ryan said. “The fact that we have very clear evidence now on the effectiveness of the drugs, we need to get that message out to communities.”

Ebola, Drugs, Congo
Two of four experimental Ebola drugs being tested in Congo seem to be saving lives, international health authorities announced Monday. Pixabay

Fauci said Regeneron and Ridgeback Biotherapeutics, which has licensed the NIH compound, told authorities enough doses are readily available.

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One issue researchers will have to analyze: Occasionally people who receive the Ebola vaccine still become sick, including some in the treatment study, which raises the question of whether their earlier protection inflated the drugs’ survival numbers. (VOA)