Rats were treated with LMWHs alone or followed by short-time intravenous infusion of HBC, and bleeding time and antifactor Xa activity were measured. Male Wistar rats were observed for up to 4 days after HBC administration for clinical evaluation, gross necropsy, and biochemistry and histopathological analysis. The rat cardiomyocytes and human endothelial cells were used for the assessment of in vitro toxicity. HBC-LMWH complexes were characterized using zeta potential, isothermal titration calorimetry, and dynamic light scattering. In the present study, we explored the safety profile of HBC and its potential to reverse enoxaparin, nadroparin, dalteparin, and tinzaparin in human plasma and at in vivo conditions. We developed diblock heparin-binding copolymer (HBC), which can neutralize the anticoagulant activity of parenteral anticoagulants. Moreover, protamine sulfate can cause life-threatening hypersensitivity reactions. 3 Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland (B.K., J.M., J.S., A.J., D.P., A.M.) Faculty of Chemistry, Jagiellonian University, Krakow, Poland (K.K., M.N., K.S.) and Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan (S.-I.Y.) resulting from the application of low-molecular-weight heparins (LMWHs) may be treated with protamine sulfate, but this treatment lacks efficiency its action against antifactor Xa activity is limited to ∼60%.3 Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland (B.K., J.M., J.S., A.J., D.P., A.M.) Faculty of Chemistry, Jagiellonian University, Krakow, Poland (K.K., M.N., K.S.) and Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan (S.-I.Y.) 1 Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland (B.K., J.M., J.S., A.J., D.P., A.M.) Faculty of Chemistry, Jagiellonian University, Krakow, Poland (K.K., M.N., K.S.) and Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan (S.-I.Y.) 2 Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland (B.K., J.M., J.S., A.J., D.P., A.M.) Faculty of Chemistry, Jagiellonian University, Krakow, Poland (K.K., M.N., K.S.) and Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan (S.-I.Y.).1 Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland (B.K., J.M., J.S., A.J., D.P., A.M.) Faculty of Chemistry, Jagiellonian University, Krakow, Poland (K.K., M.N., K.S.) and Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan (S.-I.Y.) 2 Department of Pharmacodynamics, Medical University of Bialystok, Bialystok, Poland (B.K., J.M., J.S., A.J., D.P., A.M.) Faculty of Chemistry, Jagiellonian University, Krakow, Poland (K.K., M.N., K.S.) and Department of Applied Chemistry, Graduate School of Engineering, University of Hyogo, Himeji, Hyogo, Japan (S.-I.Y.).
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