11 July 2018

Medicines in a shell

Cerium dioxide nanoparticles protect microcapsules with medications from aggressive substances

Tatiana Perevyazova, ITEB RAS Press Service

The development of new effective targeted drug delivery systems is one of the most promising ways to improve the treatment of socially significant diseases.

Joint work of scientists from the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences (ITEB RAS), the N. S. Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences (IONH RAS), Tomsk State University together with foreign colleagues from the D.K. Zabolotny Institute of Microbiology and Virology (IMV NASU) and Queen Mary University of London with the support of the RNF represents an innovative approach to the production of composite microcapsules with enhanced protective functions.

An article on this development was published in the May issue of ACS Applied Materials & Interfaces magazine.

Many medicines, getting into our body, are exposed to various substances that are aggressive to them, which significantly reduces their effectiveness. For this reason, it is necessary to increase the dosage of medicines. Some of them have a number of undesirable side effects, and there are also those that are very toxic to the body, for example, chemicals with which they fight malignant tumors. The way out of this situation is the targeted delivery of pharmaceuticals directly to the organ that needs to be cured. This is done with the help of microcapsules that protect medicines when delivered to the target zone through aggressive media. Moreover, such microcapsules provide the possibility of controlled release of their contents.

Currently, there are various variants of 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 6-8 layers of polyelectrolytes, capsules become stable – they retain their structure after removal of the calcium carbonate substrate and can be used as microcontainers. However, the polyelectrolyte shell of microcapsules provides only "passive" protection of encapsulated substances, unable to withstand aggressive environments. In the new work, scientists proposed using cerium dioxide nanoparticles with unique antioxidant properties as one of the layers of polyelectrolyte. They have already demonstrated earlier 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 protein activity would remain after processing such capsules with an aggressive agent – hydrogen peroxide in high concentration. The researchers found that the protective effect depends on the content of cerium dioxide 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 core with the active substance – from filtration of reactive oxygen species to their complete blocking.

CeO2.gif

Scheme of "active" protection of nanoengineered polyelectrolyte capsules. Left: Hydrogen peroxide penetrates the shell and destroys luciferase in the microcapsule nucleus. Right: Cerium dioxide nanoparticles prevent hydrogen peroxide from entering the microcapsule core by decomposing it on the microcapsule surface. Figure from an article in ACS Appl Mater Interfaces.

Researcher at the Laboratory of Cell and Tissue Growth of ITEB RAS, Candidate of Biological Sciences Anton Popov says: "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. These microcapsules are non-toxic and able to protect cells from oxidative stress caused by hydrogen peroxide."

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

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