Antithrombogenic properties of bioconjugate streptokinase-polyglycerol dendrimers

Abstract

Dendrimers are monodisperse, spherical and hyperbranched synthetic macromolecules with a large number of surface groups that have the potential to act as carriers for drug immobilization by covalent binding or charge transfer complexation. In this work, a bioconjugate of streptokinase and a polyglycerol dendrimer (PGLD) generation 5 was used to obtain fibrinolytic surfaces. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography (GPC), nuclear magnetic resonance (1H-NMR, 13C-NMR) and matrix assisted laser desorption/ionization (MALDI-TOF) techniques. The synthesized dendrimer presented low dispersion in molecular weights (Mw/Mn = 1.05) and a degree of branching of 0.82 which characterize the polymer dendritic structure. The blood compatibility of the bioconjugate PGLD-Sk was evaluated by in vitro assays such as platelet adhesion and thrombus formation. Uncoated polystyrene –microtitre plates (ELISA) was used as reference. The epifluorescence microscopy results indicate that PGLD-Sk coating showed an improved antithrombogenic character relative to the uncoated ELISA plates.