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- For the time being: new technology will reduce the side effects of tumor treatment
For the time being: new technology will reduce the side effects of tumor treatment
Russian scientists have created "smart" programmable carriers with microscopic pores for the point delivery of drugs in the body. The technology allows you to set the key parameters of the system in advance, controlling the sensitivity of nanoplatforms to the acidity of the medium and magnetic fields. This makes it possible to ensure the controlled release of drugs. It is expected that the development will reduce the negative effects of drugs on the body and reduce side effects. At the same time, experts emphasize that when implementing the technology, it is necessary to take into account the potential toxicity of the magnetic core and confirm the reproducibility and predictability of the behavior of such particles.
How to create targeted drug delivery systems in the body
Scientists at the Moscow Aviation Institute, together with colleagues from a number of Russian research organizations, have created innovative programmable systems for targeted drug delivery to the outbreak.
— The development is based on stimulus-sensitive nanocomposites. These are "smart" materials that change their properties under the influence of external factors such as temperature, acidity, and others. Such systems make it possible to deliver the drug in a controlled manner, reducing the toxic effect on the body," said Artur Dzeranov, an assistant at the Department of Advanced Materials and Technologies for Aerospace Applications at MAI.
Artur Dzeranov, Assistant Professor at the Department of Advanced Materials and Technologies for Aerospace Applications, MAI
The technology involves the use of special nanoscale media. Their outer shell consists of silica with microscopic pores, and medicine and special magnetic particles are placed inside, he explained.
At the same time, the surface of the carriers has a negative charge, the same as that of the blood components. This allows them to "disguise" themselves and move freely through the body, avoiding being captured by cells of the immune system and excreted from the body.
— Many stimulus-sensitive systems respond to a single trigger. Our group is developing "intelligent" platforms that combine two independent control mechanisms at once," said Artur Dzeranov.
The first method is based on the effect of a magnetic field, which allows particles to accumulate directionally in the target organ, the expert explained. The second mechanism is related to sensitivity to the acidity of the environment: for example, an increase in the level of hydrogen peroxide is characteristic of inflammatory processes and tumors. Due to this property, carriers are able to recognize the pathological focus, open the pores and release the medicinal substance directly in the affected area.
— The special feature of the development is the flexibility of the architecture. By changing the composition of the components and the order in which they are applied, it is possible to precisely program the size, composition, and shape of the "containers" and thereby adjust the rate of drug release and drug delivery to the desired organ, the scientist said.
According to him, the use of machine learning methods makes it possible to accelerate the prediction of the properties of such systems. In the future, knowing the data of a particular patient, it is possible to individually program the media parameters.
The project is currently at the stage of preclinical studies, the scientist said. A drug based on the widely used antibiotic ciprofloxacin was studied as a model. The tests have shown that the developed systems are more effective than the drug itself in its pure form, acting against E. coli and a number of other bacteria.
In the near future, we plan to study the stability of nanocomposites in various media, including in the presence of proteins. In addition, the developers intend to expand the list of medicines that can be delivered using the new system.
How technology reduces drug toxicity
— Drugs for the treatment of tumors are toxic and act on healthy cells. Targeted delivery avoids this effect. At the same time, silica is a neutral compound that is excreted unchanged from the body. It is important that scientists have solved the problem of the destruction (biodegradation) of nanoparticles by the body's immune system due to the "invisible cap" in the form of a negative charge," said Anna Marakhova, professor at the Institute of Pharmacy and Biotechnology at the P. Lumumba Peoples' Friendship University of Russia.
According to her, the controlled release of the drug will reduce the frequency of taking the drug and reduce the risk of side effects.
The advancement of the development largely depends on the willingness of investors to finance clinical trials, registration and launch of the drug on the market, the expert added. In general, it takes considerable time and the participation of a large number of specialists to confirm the effectiveness and safety.
According to Andrey Karmanov, Associate Professor of the Department of Nano- and Microelectronics at Penza State University, a number of limitations must be taken into account when implementing such systems. In particular, nanocomposites may be toxic due to the magnetic core, which requires additional testing. In addition, it is important to increase the accuracy of delivery, since magnetic fields do not always ensure reliable localization of nanoparticles in the affected area. Improvement of drug encapsulation and controlled release methods is also required.
— Magnetic porous silica carriers with pH-sensitive release are already known in science. The novelty of the approach lies in the specific architecture of the systems, the combination of functions and the possibility of fine—tuning them," Albert Rizvanov, head of the Personalized Medicine Center of Excellence at the Institute of Fundamental Medicine and Biology at Kazan (Volga Region) Federal University, explained to Izvestia.
He called the use of machine learning methods to predict the structure and behavior of such media particularly promising.
According to him, when implementing the technology, it is necessary to prove that particles behave predictably in a living organism. Another limitation is the decrease in the effectiveness of the external magnetic field with depth, which is why the use of such systems is primarily possible for foci located close to the surface of the body.
— The development is in demand when using drugs with high toxicity, a narrow therapeutic window, low penetration into the target tissue or the need to locally maintain a high concentration of the active substance. These are antitumor drugs, some antibiotics, anti—inflammatory drugs, as well as photosensitizers and other molecules for local combination therapy," the expert commented.
In his opinion, such systems are most effective in localized processes, where there is a clearly defined focus to which the carrier can be delivered and where the microenvironment differs from the normal one. For example, these are solid (solid) tumors, inflammations, infections, as well as individual ischemic lesions.
Carriers that react to pH, enzymes, redox environment, light, temperature, magnetic field and their combinations are actively developing, the specialist said. The strength of such platforms is the ability to combine spatial control of delivery with temporal control of release. Multitimulus systems are particularly promising.
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