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Magnetically targeted thrombolysis with recombinant tissue plasminogen activator bound to polyacrylic acid-coated nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
10014 658 2009 9 PDF Available
Title
Magnetically targeted thrombolysis with recombinant tissue plasminogen activator bound to polyacrylic acid-coated nanoparticles
Abstract

We investigated the feasibility and efficacy of target thrombolysis with recombinant tissue plasminogen activator (rtPA) covalently bound to magnetic nanoparticle (MNP) and retained to the target site in vivo by an external magnet. Polyacrylic acid-coated magnetite (PAA–MNP, 246 nm) was synthesized and characterized; rtPA was immobilized to PAA–MNP through carbodiimide-mediated amide bond formation. The enzyme activities of the bound rtPA, as measured by a chromogenic substrate assay and 125I-fibrinolysis assay, were 87 ± 1% and 86 ± 3% of that of free rtPA. Under guidance with the magnet moving back and forth along the iliac artery, the thrombolytic activity of PAA–MNP–rtPA with rtPA equivalent to 0.2 mg/kg was determined by flowmetry in a rat embolic model. Intra-arterial administration of PAA–MNP–rtPA restored the iliac blood flow within 75 min to 82% of that before the clot lodging, whereas equivalent amount of PAA–MNP or free rtPA exerted no improvement on hemodynamics. At the end of 2-h period, PAA–MNP–rtPA did not alter levels of hemoglobin, hematocrit, or blood cell count. In conclusion, immobilization of rtPA to PAA–MNP with covalent binding resulted in a stable rtPA preparation and predictable amount of rtPA around the target site under magnetic guidance; this approach may achieve reproducible and effective target thrombolysis with <20% of a regular dose of rtPA.

Keywords
Embolism; Thrombolysis; Fibrinolysis; Tissue plasminogen activator; Nanoparticle
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Magnetically targeted thrombolysis with recombinant tissue plasminogen activator bound to polyacrylic acid-coated nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 19, July 2009, Pages 3343–3351
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us