The researchers stated in a paper published online on March 8 in the peer-reviewed journal Acta Pharmaceutica Sinica B that the nanodrug effectively mitigates kidney injury in mice induced with injury.
Nano delivery systems represent a rapidly evolving field of science that utilizes nanoscale materials to deliver therapeutic agents to specific targeted sites in a controlled manner.
Acute kidney injury occurs when the kidneys abruptly cease functioning properly, typically within a few days. If left untreated or in severe cases, it can progress to chronic kidney disease or failure.
While clinics offer supportive management like dialysis and blood pressure maintenance for acute kidney injury, targeted medications and related treatments were lacking, as mentioned in the paper.
The researchers, including Tu Yingfeng, a professor at Southern Medical University and an author of the study, believe that precise treatment targeting the pathogenesis of acute kidney injury proves to be an effective solution.
Their previous research had identified a group of metabolism-related microbial molecules known as piericidins, derived from marine strains of Streptomyces bacteria, that exhibited potential in treating kidney cancer.
One of these molecules, S14, demonstrated efficacy in treating acute kidney injury in mice by enhancing the production of PRDX1, an antioxidant enzyme that regulates oxidative stress.
According to the paper, oxidative stress, which can lead to inflammation and cell death, is considered the primary contributor to acute kidney injury.
However, a significant limitation of S14 was identified by the researchers – the rapid processing and excretion of the bacteria from the body, resulting in poor treatment efficiency.
To address this issue, the team aimed to enhance the absorption, distribution, metabolism, and excretion of S14 by developing a drug delivery platform that could improve its absorption rate and extent to better target the injury.
Chitosan, a sugar derived from the outer skeleton of shellfish like shrimp, crab, and lobster, was selected as the carrier for S14 due to its exceptional biocompatibility and biodegradability.
The researchers developed a nanodrug using two marine-derived molecules to enhance the druggability of the S14 candidate, enabling it to accumulate in injured tissue and release slowly.
This involved modifying the chitosan to be pH-sensitive, enabling it to target cells overexpressing kidney injury molecules.
In experiments conducted on mice with induced acute kidney injury, the nanodrugs effectively alleviated oxidative stress, protected mitochondria, reduced inflammation, and decreased cell death, without causing apparent organ damage or toxicity to the kidneys.
The team’s study outlines a systematic approach to marine medication development, suggesting that integrating drug candidates with optimization could offer a viable strategy for clinically treating acute kidney injury.
Tu expressed hope that further research and refinement could pave the way for the clinical application of their drug.