Thrombin@Fe3O4 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. Prepared colloids show protrombotic activity and cause plasma coagulation in in vitro experiments. We also show here using a model blood vessel that the THR@ferria composite does not cause systematic thrombosis due to low activity, but being concentrated by an external magnetic field with simultaneous fibrinogen injection accelerates local hemostasis and stops the bleeding. For instance, a model vessel system with circulating blood at the puncture of the vessel wall and the application of a permanent magnetic field yielded a hemostasis time by a factor of 6.5 shorter than that observed for the control sample. Biocompatibility of composites was tested on HELF and HeLa cells and revealed no toxic effects.

Composites based on heparin and MIL-101(Fe): the drug releasing depot for anticoagulant therapy and advanced medical nanofabrication.

We describe the synthesis and properties of a new composite material based on heparin and MIL-101(Fe) metal-organic framework. The intrinsic instability of MIL-101(Fe) towards hydrolysis enables binding of heparin molecules to the framework structure as is evidenced by DFT calculations and adsorption experiments. The de novo formed heparin-MOF composites showed good biocompatibility in in vitro and demonstrated pronounced anticoagulant activity. The specific interaction between the bioactive molecule and the carrier is critical for the selective degradation of the complex in the body fluids and for the enhanced activity. Hep_MIL-101(Fe) composite could serve as a drug-releasing depot for nanofabrication and to introduce anticoagulant activity to medical devices and biocoatings. Addition of Hep_MIL-101(Fe) to a sol-gel derived thrombolytic matrix allowed the combination of anticoagulant and thrombolytic activities in a single hybrid nanomaterial that could be applied as a bioactive nanocoating for PTFE vein implants.