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Scientists have proposed a method for intracellular drug delivery using natural nanobubbles (vesicles). They were isolated from apple juice and from human cell cultures. Such biocontainers do not cause an immune response, are non-toxic, easy to obtain and stable when stored for up to five months. They accumulate in cells for up to seven days, which will make it possible to create long-acting drugs. According to experts, in order to bring the development to clinical use, it is necessary to solve the problems of stability of loaded vesicles and standardization of their production.

Nanobubbles will help deliver drugs to the body

Russian scientists have isolated vesicles (nanobubbles that cells use to exchange information and biomolecules with each other) from apple juice and from a liquid in which different human cells were grown, both healthy embryonic and cancerous. The resulting structures do not cause an immune response and are non-toxic. At the same time, they are relatively easy to obtain, the Russian Ministry of Education and Science told Izvestia.

— Biological nanomaterials have long been used for intracellular drug delivery. They are used to destroy viruses and some bacteria capable of multiplying in human cells (these are chlamydia, rickettsia, mycoplasma, etc.). All cells are able to capture nanomaterials by means of indentations of the outer membrane, the so—called endocytosis," Olga Morozova, a leading researcher at the Laboratory of Medical Nanotechnology at the FNCC FHM, told Izvestia.

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Photo: IZVESTIA/Pavel Volkov

However, most of these objects enter lysosomes after being captured by cells. These are special cellular organelles that contain more than 60 aggressive enzymes for the degradation of all foreign substances. In addition, during the destruction of such substances, the cell releases signaling molecules (interferons), which "order" the immune system to destroy the cell with foreign materials, she explained.

— To circumvent the obstacle, the researchers isolated extracellular vesicles of plant and animal origin ranging in size from 20 to 200 nm from homemade apple juice. To add drugs, natural vesicles were destroyed, dried in a thin layer, and membrane membranes were restored in the presence of various substances and nanoparticles," explained Ekaterina Obraztsova, Deputy head of the Laboratory of Functional Biomaterials at MIPT.

Experiments have shown that the obtained plant vesicles are non-toxic to humans and do not cause an immune response, she said. In addition, they can accumulate in cells for seven days, thereby achieving a long-term effect of the drug. Also, such biocontainers, unlike other technologies, are relatively easy to manufacture and stable when stored for up to five months.

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Photo: IZVESTIA/Sergey Lantyukhov

Staff from the Institute of Biophysics of the Future of the Moscow Institute of Physics and Technology, the N.F. Gamaleya National Research Center for Epidemiology and Microbiology and the Y.M. Lopukhin Federal Center for Physico-Chemical Medicine of the Federal Medical and Biological Agency participated in the development.

How to turn a development into a real drug

— The advantage of natural extracellular vesicles is that they mimic the natural mechanism of intercellular transport. It is important that apple juice is used as an affordable source. Human vesicles traditionally have a low yield, so plant sources are interesting as cheaper and more widespread, but it is necessary to separately check the immunogenicity, the presence of foreign proteins and antigens, distribution in the body and safety during repeated administration," explained Izvestia head of the Center of Excellence "Personalized Medicine" of Kazan (Volga Region) Federal University, corresponding member Albert Rizvanov of the Academy of Sciences of the Republic of Tatarstan.

The research is not a breakthrough, but an important methodological work, he noted. In the experiment, loaded vesicles were less stable, and part of the peptide load was released already in the first three days, which is important to take into account when creating a real drug.

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Photo: IZVESTIA/Sergey Lantyukhov

According to the expert, in practice, the proposed platform may be in demand in oncology, the delivery of messenger RNA, proteins, peptides and other molecules, as well as in personalized medicine. However, it is necessary to go through the stages of preclinical verification, standardization of the composition and proof of targeted delivery to the right cells.

— In addition to the already mentioned advantages, we can say that the drug enclosed in the vesicle is protected from destruction by blood enzymes and is not subject to dilution. If nanocapsules are additionally modified with navigation molecules, they can be selectively accumulated in affected cells without affecting healthy tissues. However, the technology has a number of limitations. So, only a small dose of the drug is placed in one vesicle, while it is extremely difficult to ensure complete uniformity of such bubbles. In addition, the membrane may lose its tightness in the bloodstream, which will lead to premature release of the drug," said Evgeny Kurdyukov, Associate professor of the Department of General and Clinical Pharmacology at Penza State University.

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Photo: IZVESTIA/Sergey Lantyukhov

According to him, the method can be used in the treatment of oncological diseases, since vesicles are able to accumulate independently in tumor tissues. The next stage is the creation of "smart" biocontainers: for this, it is planned to attach beacon molecules to their surface that recognize exclusively affected cells. Another promising area is related to the development of hybrid structures combining apple and human vesicles to combine their advantages. In addition, it is necessary to build a quality control system that will ensure stable safety and efficiency of each batch.

Переведено сервисом «Яндекс Переводчик»

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