Researchers have synthesized microgels that can deliver drugs directly to the kidneys to treat chronic kidney disease. The microgels, which contain natural proteins and oils, have been shown to be non-toxic to different types of cells in the kidney. The experiments also showed that the microgels can be injected into the bloodstream, making targeted drug delivery faster and less of a nuisance for the patient. The research, supported by grants #23-75-10070 and #21-75-10042 from the Russian Science Foundation (RSF), was published in the journal Optical Materials.

Chronic kidney disease is a general term for a number of kidney problems. Unhealthy kidneys are unable to filter the blood properly, leading to a build-up of metabolites and toxins, higher blood acidity, tissue damage, and increased blood pressure. Drugs used to treat chronic kidney disease are often quite toxic, affecting other individual organs and the entire human system. Scientists are therefore trying to develop systems that can deliver drugs directly to the damaged kidney.

Researchers from the Skolkovo Institute of Science and Technology (Moscow), Chernyshevsky Saratov State University (Saratov) and Ogaryov Mordovia State University (Saransk) have synthesized microgels for drug delivery to the kidneys based on a combination of milk whey proteins. They mixed it with linseed oil and a safe fluorescent dye to facilitate further monitoring of the accumulation and movement of the microgels in the tissue. The resulting emulsion microparticles consisted of an oil phase and a protein shell. Thanks to its physical and chemical properties, the resulting mixture, once introduced into the body, was transported directly to the kidneys.

The team studied the toxicity of the microgels by adding them to human embryonic kidney cells, connective tissue cells called fibroblasts, stem cells, and immune cells and storing the samples for three days. The researchers chose these four cell types because they are typically found in normal animal and human kidneys. The experiment showed that the microgels, even at high concentrations, did not affect cell viability.

The researchers then tested their method on mice, dividing them into three groups. In the first group, they injected the suspension into the tail vein and in the second into the left renal artery, while the third group served as a reference.

Looking at how the microgels spread in the mouse organism, the researchers discovered that regardless of the injection method, the drug reached the kidney and began to accumulate there within five minutes after injection. Unexpectedly, arterial injection resulted in greater accumulation of microgels in the opposite kidney – an effect largely due to the blood flow response to local injection of microgels. Nevertheless, the injection had no adverse effects on the kidneys or any other vital organs. After about 24 hours, a significant amount of the microgels, which have been destroyed and processed by enzymes, are eliminated from the body, facilitating the local release of the drug delivered to the kidney by the new method. The researchers suggested chemically ‘stitching’ the drugs onto the surface of microparticles or loading them into oil droplets.

 “The proposed delivery method ensures that the drug accumulates in the kidneys, without affecting other organs. The microgels are non-toxic because they contain natural components that are safe for living cells. In addition, our experiments showed that the microgels can be injected intravenously − a technique that is the fastest, most accurate and least stressful for the patient. In the future, we plan to test drug-loaded microgels in the treatment of various kidney diseases of an infectious, immunological and oncological nature,” says Olga Sindeeva, a senior research scientist at the Skoltech Neuro Center, an author of the paper, and a leader in the project funded by the RSF grant.