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Title: Urokinase -CdSe/ZnS core/shell conjugates for targeted fibrinolytic treatment: An in vitro evaluation
Authors: Painuly, D
Bhatt, A
Krishnan, VK
Issue Date: Oct-2014
Publisher: Journal of Biomaterials & Tissue Engineering.
Citation: Journal of Biomaterials & Tissue Engineering. 2014;4(10):823-833.
Abstract: Cardiac diseases are one of the major causes of mortality worldwide. The conventional fibrinolytic therapy using drugs causes fibrinolysis in a non-specific and uncontrolled manner limiting the therapeutic potential of this therapy. If the drugs used can be specifically targeted and released in a controlled fashion at the site of the clot, a better therapeutic potential can be expected. In this study, we have monitored in vitro clot lysis generated by a quantum dot [Q-dot] based targeted drug delivery system. Urokinase, a plasminogen activator was conjugated with CdSe/ZnS core–shell (CS) by carbodimide coupling method to form urokinase-core/shell conjugate (UK-CS conjugate). These conjugates were characterized using X-ray diffraction (XRD), Dynamic Light Scattering (DLS), Fourier-Transform Infrared Spectroscopy (FT-IR), absorption and Photoluminescence (PL) spectroscopy. The optimum entrapment efficiency (E. E) was found to be ∼96% and the conjugate was found to be stable at 4 °C for 20 days of storage. The storage stability was determined in terms of size, absorbance and encapsulation efficiency. In vitro drug release studies exhibited controlled sustained release of UK from conjugate. In vitro thrombolysis testing on the plasma clot was carried out at different dose concentrations (18, 36 and 72 μg) of UK and UK-CS conjugate and the efficacy of UK-CS was found similar to bare UK at higher concentrations. Accelerated thrombolysis was observed in UK-CS-Ab system by binding the drug carrier specific to the clot using anti—fibrin antibody (Ab). Clot lysis time was found to decrease and comparable to UK even at 18 μg level compared to UK-CS conjugate. Thus, the proposed conjugate system based upon CS drug carriers may find potential use in therapeutic applications of thrombolytic diseases.
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