The nanodrug “alleviates kidney injury efficiently” in injury-induced mice, the researchers wrote in a paper published online on March 8 in the peer reviewed journal Acta Pharmaceutica Sinica B.
Nano delivery systems are a rapidly developing area of science where nanoscale materials can be used to deliver therapeutic agents to specific targeted sites in a controlled manner.
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Acute kidney injury happens when the kidneys suddenly stop working properly, usually in less than a few days. In severe cases, or if the condition is not properly treated, it can advance to chronic kidney disease or failure.
While supportive management such as dialysis and blood pressure maintenance for acute kidney injury were available in clinics, targeted medications and related treatment were not, the paper said.
“We believe that precise treatment targeting the pathogenesis of acute kidney injury is an effective solution,” said Tu Yingfeng, an author of the study and a professor at Southern Medical University.
Previous work by the scientists had identified a family of metabolism-related microbial molecules called piericidins, which they derived from marine strains of the Streptomyces bacteria, that showed promise in treating kidney cancer.
Among them was S14, which was found to be useful in treating acute kidney injury in mice by increasing the production of PRDX1, an antioxidant enzyme that can regulate oxidative stress.
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Oxidative stress can cause inflammation and cell death and is considered the leading contributor to acute kidney injury, according to the paper.
But S14 has a major drawback. The researchers determined that the bacteria is processed and excreted from the body very rapidly, “ultimately resulting in poor treatment efficiency”.
To improve the absorption, distribution, metabolism and excretion of S14, the team aimed to develop a drug delivery platform that would improve the extent and rate of absorption to better target the injury.
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Living with kidney failure in China
Living with kidney failure in China
Chitosan – a type of sugar from the outer skeleton of shellfish such as shrimp, crab and lobster – was chosen as the carrier for S14 because of its “excellent biocompatibility and biodegradability”, the paper said.
The nanodrug was developed using the two marine-derived molecules to “improve the druggability” of the S14 drug candidate, allowing it to accumulate in injured tissue and be released more slowly.
This included modifying the chitosan to make it pH-sensitive, causing it to target cells that overexpressed kidney injury molecules, Tu said.
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The researchers said the nanodrugs “effectively alleviate oxidative stress, protect mitochondria, mitigate inflammation” and reduce cell death when tested in mice with induced acute kidney injury.
No obvious damage to organs was found in mice that were given the nanodrug, suggesting that it was biosafe and not toxic to the kidneys, the paper said.
Tu said the team hoped further research and optimisation could lead to a clinical application of their drug.
