Nanoparticles protect drugs from aggressive oxidation

Scientists presented an innovative approach to the production of composite microcapsules with enhanced protective functions. Cerium dioxide structures can protect drugs from the external environment, and with their help, it will be possible to deliver drugs directly to the site of the disease. An article on this development was published in ACS Applied Materials & Interfaces. The research was supported by a grant from the Russian Science Foundation.

Many drugs that enter our body are affected by various substances that are aggressive for them. Because of this, their effectiveness is significantly reduced and therefore doctors have to increase their dosage. This poses a danger to the body, since some of the drugs can also act negatively on it – for example, due to their side effects or toxicity (the latter is characteristic of substances that fight malignant tumors). Accordingly, the more such drugs enter the body, the higher the risk that they will not only cure, but also harm.

Targeted delivery of pharmaceuticals directly to the organ to be treated helps to solve this problem. This is done using microcapsules that protect the drug from aggressive substances when delivered to the target. Thanks to such microcapsules, it is also possible to release their contents in a controlled manner.

There are now various options for such microcapsules. One of the most promising developments is polyelectrolyte microcapsules. They are formed as follows: polymers with different charges are alternately layered on a calcium-carbonate substrate. With six to eight layers of polyelectrolytes, the capsules become stable – they retain their structure after removing the calcium-carbonate substrate and can be used as microcontainers. However, the polyelectrolyte shell of the microcapsules provides only “passive” protection of the encapsulated substances, which cannot withstand aggressive media. In a new work, scientists have proposed using cerium dioxide nanoparticles, which have unique antioxidant properties, as one of the polyelectrolyte layers. They had previously demonstrated that these nanoparticles are non-toxic to normal mammalian cells and have great therapeutic potential.

Scientists enclosed the bioluminescent enzyme luciferase in a polyelectrolyte capsule with a layer of cerium dioxide nanoparticles and checked whether the activity of the protein would remain after treatment of such capsules with an aggressive agent – hydrogen peroxide in a high concentration. The researchers found that the protective effect depends on the cerium dioxide content in the shell. By varying the concentration of nanoparticles on the surface of the microcapsule, it is possible to control the level of shielding of the nucleus with the active substance – from filtration of reactive oxygen species to their complete blocking.

“We conducted a comprehensive analysis of the physicochemical properties of microcapsules with cerium dioxide nanoparticles and encapsulated luciferase and showed that they are easily perceived by rat neuronal cells,” says co-author Anton Popov from ITEB RAS. “These microcapsules are non-toxic and can protect cells from oxidative stress caused by hydrogen peroxide.”

In their work, scientists have shown that the active protection of microencapsulated substances by cerium dioxide nanoparticles is very promising for the development of new drug delivery systems and for the diagnosis of various diseases, including those in aggressive environments.

The work was carried out by scientists from the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences (ITEB RAS), the Institute of General and Inorganic Chemistry named after N. FROM. Kurnakov RAS (IGIC RAS), Tomsk State University together with foreign colleagues from the Institute of Microbiology and Virology named after D.K. Zabolotny (IMV NASU) and Queen Mary University of London