Improving long circulation and procoagulant platelet targeting by engineering of hirudin prodrug.
作者： Hu-Hu Han , Hai-Tao Zhang , Ru Wang , Yi Yan , Xiaoyan Liu
DOI: 10.1016/J.IJPHARM.2020.119869
关键词:
摘要: Abstract To reduce systemic bleeding risks during anticoagulant treatment, a new concept named “precise anticoagulation” was proposed to localize the effects of anticoagulants via targeted delivery prodrugs coagulation site. In this study, fusion protein Annexin V–hirudin 3-ABD (hAvHA) constructed achieve prolonged circulation and hirudin sites. hAvHA inactive as prodrug, it could bind albumin circulation. The drug quickly activated factor Xa-mediated cleavage once occurred, efficiently released exert antithrombin activity in vitro. be mouse blood significant anticoagulation effects. results FITC labeling illustrated that bound procoagulant platelets, suggesting V modification permits sites thrombosis. vitro with an equilibrium dissociation constant 8 pM, ABD permitted vivo. Moreover, time much shorter hAvHA-treated mice than hirudin-treated mice. Therefore, our suggested is potential promising
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