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Magnetically controlled drug effectively targets and dissolves blood clots

Posted: 23 June 2016 | Victoria White, Digital Content Producer | No comments yet

Scientists have developed a magnetically controlled drug that can be condensed on a blood clot by means of a magnetic field…

The influence of the new thrombolytic system on vascular thrombus extracted during the operation. CREDIT: ITMO University

Scientists from ITMO University in cooperation with Mariinsky Hospital in Saint Petersburg have developed a magnetically controlled drug that can be condensed on a blood clot by means of a magnetic field.

The scientists say the new drug is safe for intravenous injection and can dissolve clots up to 4000 times more efficiently than ordinary enzyme-based drugs. They also say the compound will help reduce drug dosage, thus avoiding numerous side effects.

In emergency situations caused by thrombosis, the clot has to be destroyed within a very short period of time – about 3 to 4.5 hours. After that, tissues die without blood flow. But even if the patient was lucky enough to undergo thrombolysis, they will get numerous complications caused by the thrombolytic drug – a specific enzyme injected intravenously to dissolve blood clots.

The challenge is that thrombolytic drugs do not target the clot, but rather spread over the whole circulatory system. The body begins to block the foreign enzyme, quickly diminishing its activity. Therefore, the drugs are injected in knock-out doses in hope that at least a small portion will reach the blood clot on time. 

Ivan Dudanov, head of the regional cardiovascular center of Mariinsky hospital, explained: “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”.

A porous magnetite framework

The scientists produced a composite material, which can deliver thrombolytic enzymes in a safe and targeted manner. The new material is composed of a porous magnetite framework and molecules of urokinase – an enzyme frequently used in medicine as a thrombolytic agent. The composite can be used to create thrombolytic coating for artificial blood vessels and stable injectable solutions made of nanosized particles that can be easily localised near the clot by means of an external magnetic field.

clot

Schematic image of thrombolytic drug nanoparticles. The enzyme is surrounded by magnetite framework. CREDIT: ITMO University

Importantly, the magnetite framework also protects enzymes from various inhibitors that are present in the blood and can deactivate thrombolytic medications. Andrey Drozdov, researcher at the Laboratory of Solution Chemistry of Advanced Materials and Technologies, notes: “Usually, in order to achieve a prolonged effect for such drugs, the enzyme is placed inside a polymeric matrix. The enzyme is then gradually released from the matrix and eventually loses all activity. We, on the other hand, experimentally demonstrated that enzymes protected using our approach 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.”

The researchers say the material is potentially safe for humans, because it is made of components that already have permission for intravenous injection. According to professor Dudanov, future drugs based on the new composite could be used not only for thrombosis treatment, but also for its prevention. Circulating in the blood even in small amounts, the enzyme can gently clean the vessels and will stay active for a very long time until it is naturally excreted through liver like an ordinary metabolite.

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