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MOSCOW, June 20. /TASS/ The scientists from the Saint Petersburg National Research University of Information Technologies, Mechanics and Optics (ITMO), together with the Saint-Petersburg Municipal Mariinsky Hospital have created a magnetically controlled drug for curing thrombosis based on a magnetite matrix with encapsulated thrombolytic enzyme, as reported the popular-science web portal "Cherdak" at TASS, with the reference to the press service of ITMO.
The solution of nanosized drug localized near the clot by means of an external magnetic field can dissolve blood clots up to 4000 times more efficiently than ordinary enzyme-based drugs. The results of the research have been published in Scientific Reports.
"The researchers have created a material guaranteeing directional and safe for an organism delivery of thrombus degradation enzyme, that enables lowering dosage and avoiding many side effects," reported in the press release.
Up to 60% of fatal cases among patients in Russia are caused by heart and apoplectic attacks, the two most dangerous thrombus diseases connected with the vascular occlusion. One of the main objectives of emergency assistance in such conditions is to maintain a thrombolysis, i. e. to dissolve the clot quickly. However, only 2% of Russian patients brought to the hospital can successfully undergo this procedure since the time of thrombus degradation is limited by 3-4.5 hours starting from the formation time. After that, tissues die without blood flow.
Influence of newly introduced thrombolytic system of the vascular thrombus extracted during the surgery.
Influence of newly introduced thrombolytic system of the vascular thrombus extracted during the surgery© The figure is provided by press service of ITMO
Moreover, the modern thrombolytics, the protein injected intravenously to dissolve thrombus, do not have a directional effect but rather spread over the whole circulatory system causing the immune reflex of the organism. Therefore, the drugs are injected in knock-out doses in hope that at least a small portion will reach the blood clot on time.
“Now, we are using a sledgehammer to crack a nut”, says Ivan Dudanov, the head of the regional cardiovascular center of Mariinsky hospital. “Dissolving a little blood clot that blocked a vessel of only 1-2 mm in diameter, thrombolytic drugs negatively affect the entire network of blood vessels. In order to change the situation, we decided to develop a method of targeted drug delivery that would allow us to considerably reduce the dosage and ensure that the whole therapeutic effect is focused on the clot.”
The new material is composed of a porous magnetite framework with enclosed protein urokinase – an enzyme frequently used in medicine as a thrombolytic agent. The composite can be used to create a thrombolytic coating for artificial blood vessels and stable injectable solutions made of nanosized particles that can be easily localized near the clot by means of an external magnetic field. The new material should be absolutely safe for a human as it consists solely of components that have been approved for intravenous injection.
Schematic view of the nanoparticle of thrombolytic medicine. The enzyme is surrounded by the magnetite frame. © The figure is provided by press service of ITMO
"We prepared a thrombolytic colloid and tested its impact on artificial blood clots taken from plasma and blood of humans, and thrombus extracted from patients in the course of the surgical intervention. The results may soon allow us to try out the new thrombolytic system on mammals. Now we are approaching preclinical studies and coordinating our project with the Ministery of Education and Sciences," - said Vladimir Vinogradov, the head of the Laboratory of Solution Chemistry of Advanced Materials and Technologies at ITMO.
According to the scientists, the new drugs could be used not only for thrombosis treatment, but also for its prevention. The composite can be used for coating artificial vessels to prevent its' occlusion. Additionally, the protein integrated in the composite is able to function for a very long period of time, as it is protected by the magnetite frame from the various inhibitors that are present in the blood. Therefore, potentially the new drug can be injected in small amounts into the vessels for therapeutic refinement even before the thrombus formation.
“Usually, while developing similar materials in order to achieve a prolonged effect, the enzyme is encapsulated inside a polymeric matrix. Then the protein is gradually released from the matrix and eventually loses all activity," said Andrey Drozdov, the first author of the study and researcher at the Laboratory of Solution Chemistry of Advanced Materials and Technologies at ITMO. "We have experimentally demonstrated that enzymes protected by composite do not lose therapeutic properties over extended periods of time and even after repeated use. The rate, at which the new drug can dissolve the clot, outperforms unprotected enzymes by about 4000 times.”