Experiments on rats carried out by Russian researchers have demonstrated that silica nanoparticles can be used to deliver drugs to the heart in case of myocardial ischemia.

One of the most promising directions in contemporary medicine is development of substances that are able to deliver drugs to a disordered organ. Nanoparticles can be used as carriers, as a lot of abnormal changed tissues selectively accumulate some substances. Research on directed drug delivery by nanoparticles is mainly carried out in oncology, but this method can be also applicable in other areas. Mikhail Galagudza and other specialists at the V.A. Almazov Federal Center of Heart, Blood and Endocrinology, St. Petersburg State Medical University and Faculty of Chemistry of St. Petersburg State University have studied possibility of directed silica nanoparticles delivery into the myocardium in case of ischemia (blood supply disturbance). Though, this was so far done on rats and without involving drugs. The article about the research will be published in the next issue of the “Russian Nanotechnologies” journal.

Silica, or silicon dioxide (SiO2), is a substance that is very widespread in nature, therefore, nanoparticles made of it will be commonly used in future. In the above research, the scientists worked with 7 nm silica particles. Specific surface of one gram of such particles makes from 170 through 380 m2. Fluorescent dye was attached to nanoparticles, so that the researchers could later watch their distribution in the organism.

Any investigation of a new substance starts with identification of its acute toxicity: it is impossible to make a drug delivery system based on particles, which could have a negative impact on the organism. To check toxicity, the nanoparticle suspension was injected to laboratory rats to assess reaction of their cardiovascular system. Having confirmed that the preparation does not have any explicit poisonous influence on the rat’s organism, the researchers embarked on the main experiment. The rats were divided into three groups. The coronary artery was pinched with the animals in the first group to simulate myocardial ischemia, and 25 minutes after that silica nanoparticles suspension was injected to them. The second group consisted of the animals, which were injected the particles suspension but their coronary artery was not pinched. The third group consisted of the intact animals, which were exposed neither to operation nor to particles injection. They were necessary in order to calculate normal silicon content in tissues.

To evaluate the result, the rats’ heart and liver was taken for analysis after the experiment was over. Nanoparticle distribution in the organism was studied via the fluorescence microscopy method, and the silicon content was estimated by the atomic absorption spectroscopy method. It has turned out that the silicon content in the heart of rats that underwent experimental ischemia is ten times higher than in the heart of intact rats, that is, silica particles selectively enter into the damaged tissue. A possible mechanism of passive directed silica nanoparticles delivery into the abnormality zone is increasing myocardium micro-vascular permeability during ischemia.

Further investigations of nanoparticles toxicity are necessary. The researchers have demonstrated that the suspension injection provides high concentration of siliceous particles in the liver, lungs and spleen. A short-term experiment is unable to show if this is dangerous for health, lengthy observation of animals is required to this end. If outcomes of further experiments are favorable, nanoparticles will be used as drug carriers. The specialists believe that they will be able to load nanoparticles with cardioprotectors (for example, bradykinin, erythropoietin, etc.), and they will selectively deliver drugs to the damaged cardiac muscle. The need in new methods for ischemic heart disease treatment is very high as heart diseases make one of the most widespread causes of people’s death.

Source of information: M.M. Galagudza, D.V. Korolev, D.L. Sonin, I.V. Alexandrov, V.N. Postnov, G.V. Papayan, E.V. Shliakhto. “Passive directed delivery of drugs into ischemic myocardium with utilization of silica nanoparticles”. “Russian Nanotechnologies”, 2010, #11-12.

Further information: Mikhail Mikhailovich Galagudza, head of scientific research laboratory of myocardium metabolism, V.A. Almazov Federal Center of Heart, Blood and Endocrinology. E-mail: galagoudza@mail.ru

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