Magnetic polyelectrolyte-based composites with dual anticoagulant and thrombolytic properties: towards optimal composition

Magnetic thrombolytic composites are a promising and rapidly developing class of nanostructured bioactive materials with plausible applications in cardiovascular diseases treatment. This class of nanoformulations can be applied to enhance the efficiency of thrombolytic agent delivery in occluded ves...

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Bibliographic Details
Published in:Journal of sol-gel science and technology 2020-09, Vol.95 (3), p.771-782
Main Authors: Drozdov, A. S., Prilepskii, A. Y., Koltsova, E. M., Anastasova, E. I., Vinogradov, V. V.
Format: Article
Language:English
Subjects:
Anticoagulants
Biocompatibility
Biomedical materials
Blood vessels
Ceramics
Chemistry and Materials Science
Coagulation
Composite materials
Composites
Composition
Glass
Heparin
In vitro methods and tests
Inorganic Chemistry
Magnetic properties
Magnetite
Materials Science
Nanoparticles
Nanotechnology
Natural Materials
Optical and Electronic Materials
Original Paper: Sol-gel and hybrid materials for biological and health (medical) applications
Polyacrylic acid
Polyelectrolytes
Polystyrene resins
Systems analysis
Thrombin
Urokinase
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Summary:Magnetic thrombolytic composites are a promising and rapidly developing class of nanostructured bioactive materials with plausible applications in cardiovascular diseases treatment. This class of nanoformulations can be applied to enhance the efficiency of thrombolytic agent delivery in occluded vessels. The main trends in this topic are aimed at the simplification of the composition, enhancement of specific activity, and completeness of action of the formulations. Herein we describe four thrombolytic systems prepared using urokinase-type plasminogen activator (uPA) conjugated to a magnetite core via polyelectrolyte molecules, namely heparin, enoxaparin, polyacrylic acid (PAA) and polystyrene sulfonate (PSS). All systems, except PSS-based, demonstrated close thrombolytic activities when taken in equivalent quantities, while the heparin based system demonstrated 30% greater activity at early stages of clot lysis. Both heparin and enoxaparin-based systems showed moderate anticoagulant activities which prolonged thrombin time from 13 to 17 s that is 3.1 and 1.5-folds lower than for equal amounts of free anticoagulants. The enoxaparin-based formulation inhibited the intrinsic coagulation pathway by 30%, while all other composites were ineffective for this purpose. These findings can be further applied for development of magnetically controlled nanomedicines with dual anticoagulant and thrombolytic properties. Highlights Highly stable magnetite hydrosols were synthesized via ultrasonically assisted co-precipitation. Magnetite nanoparticles were decorated with anionic polyelectrolytes and urokinase enzyme. Thrombolytic activity of the systems were evaluated in vitro via Thrombodynamic method.
ISSN:0928-0707
1573-4846
DOI:10.1007/s10971-020-05313-z