Self-regulated hirudin delivery for anticoagulant therapy
Drug delivery study published in Science Advances (2020)
Abstract
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
A self-regulating nanogel platform delivers recombinant hirudin in response to thrombin levels, mimicking physiological negative feedback and demonstrating anticoagulant efficacy in mouse models of pulmonary embolism and thrombosis.
Why This Matters for Hirudotherapy
This study examined a "closed-loop" nanoscale polymeric gel delivery system for recombinant hirudin, designed to enhance the protein's stability and bioavailability, target clots, and adaptively release hirudin in response to thrombin variation, with efficacy demonstrated in mouse models of pulmonary embolism and thrombosis. Because hirudin is a hallmark anticoagulant of the medicinal leech salivary secretome, this work is mechanistically relevant to hirudotherapy insofar as it explores engineering solutions to overcome hirudin's rapid clearance and improve its therapeutic index. The findings suggest that controlled-release formulation could extend the utility of leech-derived anticoagulants. However, the study used recombinant hirudin and did not involve leeches or leech saliva, and the results come exclusively from preclinical mouse models, so translation to clinical hirudotherapy remains untested and the connection is indirect.
Citation
Self-regulated hirudin delivery for anticoagulant therapy.
Xu X, Huang X, Zhang Y et al. · Science advances, 2020
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