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New magnetically controlled thrombolytic successfully passed preclinical testing

November 08, 2018

New anti-thrombosis drug based on magnetite nanoparticles developed at ITMO University was successfully tested on animals. Preclinical studies conducted in terms of the project "PHARMA 2020" showed drug's high efficacy and no side effects. Clot dissolution time of the new drug is 20 times shorter than the one of traditional medications. The range of permissible concentrations is very high, and the minimum dose of the active substance required to achieve the effect was a hundred times smaller than usual. The results are published in Applied Materials and Interfaces.

Currently, thrombosis related conditions remain the leading cause of death. There are 2 conventional ways of treatment: either surgery, requiring a complex, high-risk operation, or thrombolytics. Although this class of drugs appeared as a treatment method about 40 years ago, so far it failed to become widespread because of the side effects that occur during its systemic use. To avoid these effects, the action of thrombolytics should be localized, meaning that the drug must be delivered right to the clot. In order to do this scientists use magnetic nanoparticles.

Researchers at ITMO University developed thrombolytics based on magnetite nanoparticles coated with heparin and urokinase. Magnetite is a biocompatible iron oxide with pronounced magnetic properties. Therefore, magnetite particles movement can be controlled by a magnetic field. Urokinase is a first-generation thrombolytic with simple molecules, affordable price and efficiency almost equal to newer drugs. As soon as the nanoparticles with urokinase are injected into the blood, they can be sent to the place of clot formation using a magnetic field. Once the clot is destroyed, the magnetic field is turned off, the nanoparticles are redistributed to the liver and spleen and, finally, gradually removed.

"We initially focused on simple and inexpensive substances to make the final product affordable. Since urokinase and magnetite are equally charged, we had to use a linker. We choose heparin, an anticoagulant that often comes with thrombolytics in order to thin the blood. Typically, heparin inhibits urokinase, but we managed to avoid this effect. Preclinical trials showed that we also managed to achieve high efficiency and minimize side effects," comments Arthur Prilepskii, member of SCAMT Laboratory of ITMO University.

The new drug successfully passed preclinical studies including toxicity, allergenicity, mutagenicity, and immunotoxic tests. No side effects were identified during animal experiments. At the same time, the range of permissible drug concentrations turned out to be very high, while the minimum dose of urokinase, necessary to achieve a therapeutic effect, was approximately two orders of magnitude lower than with the introduction of the usual urokinase. Moreover, the clot dissolution time was 20 times shorter.

"Preclinical trials were conducted as part of the Pharma 2020 project. The project included 3 stages for 2 years, during which the synthesis of the drug was optimized. Moreover, we carefully studied chemical characteristics efficacy and safety of the new medication," notes Anna Fakhardo, researcher at SCAMT Laboratory of ITMO University.
-end-
Reference:

Urokinase-Conjugated Magnetite Nanoparticles as a Promising Drug Delivery System for Targeted Thrombolysis: Synthesis and Preclinical Evaluation

Artur Prilepskii et al. ACS Appl. Mater. Interfaces

https://pubs.acs.org/doi/10.1021/acsami.8b14790

ITMO University

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