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

Mortality and disabilities as outcomes of cardiovascular diseases are primarily related to blood clotting. Optimization of thrombolytic drugs is aimed at the prevention of side effects (in particular, bleeding) associated with a disbalance between coagulation and anticoagulation caused by systemically administered agents. Minimally invasive and efficient approaches to deliver the thrombolytic agent to the site of clot formation are needed.

Thrombin@FeO nanoparticles for use as a hemostatic agent in internal bleeding.

Bleeding remains one of the main causes of premature mortality at present, with internal bleeding being the most dangerous case. In this paper, magnetic hemostatic nanoparticles are shown for the first time to assist in minimally invasive treatment of internal bleeding, implying the introduction directly into the circulatory system followed by localization in the bleeding zone due to the application of an external magnetic field. Nanoparticles were produced by entrapping human thrombin (THR) into a sol-gel derived magnetite matrix followed by grinding to sizes below 200 nm and subsequent colloidization.

Streptokinase@alumina nanoparticles as a promising thrombolytic colloid with prolonged action.

The present study is devoted to the development of a new class of thrombolytic systems - nanocolloids. A non-direct plasminogen activator, streptokinase, was entrapped in a sol-gel matrix based on boehmite nanoparticles used in medical practice as the most common vaccine adjuvant. It is shown that when the enzyme content in the composite is less than 10%, only minor release is observed, while thrombolytic properties are maintained at a relatively high level, demonstrating the prolonged effect.

Leach-proof magnetic thrombolytic nanoparticles and coatings of enhanced activity.

Despite the fact that magnetic thrombolytic composites is an emerging area, all known so far systems are based on the similar mechanism of action: thrombolytic enzyme releases from the magnetic carrier leaving non-active matrix, thus making the whole system active only for a limited period of time. Such systems often have very complex structure organization and composition, consisting of materials not approved for parenteral injection, making them poor candidates for real clinical trials and implementation. Here we report, for the first time, the production of thrombolytic magnetic composite material with non-releasing behavior and prolonged action.

Synthesis of Thrombolytic Sol-Gel Coatings: Toward Drug-Entrapped Vascular Grafts.

As is evident from numerous investigations, drug-eluting vascular grafts and stents have not solved the main problems associated with thrombosis and due to drug release only postpone their advance for a longer period. Here we point to a potential solution of this problem by developing thrombolytic sol-gel coatings which potentially could lead to drug-entrapped vascular grafts: urokinase-type plasminogen activator was entrapped within a porous alumina sol-gel film with a subsequent deposition on a polymer graft.