Self-regulated hirudin delivery for anticoagulant therapy

Pathological coagulation, a disorder of blood clotting regulation, induces a number of cardiovascular diseases. A safe and efficient system for the delivery of anticoagulants to mimic the physiological negative feedback mechanism by responding to the coagulation signal changes holds the promise and...

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Bibliographic Details
Published in:Science advances 2020-10, Vol.6 (41)
Main Authors: Xu, Xiao, Huang, Xuechao, Zhang, Ying, Shen, Shiyang, Feng, Zhizi, Dong, He, Zhang, Can, Mo, Ran
Format: Article
Language:English
Subjects:
Animals
Anticoagulants - pharmacology
Blood Coagulation
Health and Medicine
Hirudins - pharmacology
Mice
Recombinant Proteins - pharmacology
SciAdv r-articles
Thrombosis - drug therapy
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Summary:Pathological coagulation, a disorder of blood clotting regulation, induces a number of cardiovascular diseases. A safe and efficient system for the delivery of anticoagulants to mimic the physiological negative feedback mechanism by responding to the coagulation signal changes holds the promise and potential for anticoagulant therapy. Here, we exploit a "closed-loop" controlled release strategy for the delivery of recombinant hirudin, an anticoagulant agent that uses a self-regulated nanoscale polymeric gel. The cross-linked nanogel network increases the stability and bioavailability of hirudin and reduces its clearance in vivo. Equipped with the clot-targeted ligand, the engineered nanogels promote the accumulation of hirudin in the fibrous clots and adaptively release the encapsulated hirudin upon the thrombin variation during the pathological proceeding of thrombus for potentiating anticoagulant activity and alleviating adverse effects. We show that this formulation efficiently prevents and inhibits the clot formation on the mouse models of pulmonary embolism and thrombosis.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.abc0382