Abstract Number: PB0061
Meeting: ISTH 2021 Congress
Background: PAMAM dendrimers are promising nanocarriers for drug delivery. They can interact with plasma proteins and affect the activity of enzymes. It is known that high-generation cationic dendrimers can cause platelet aggregation, inhibit thrombin generation, and cause the formation of fibrinogen aggregates. The mechanism of this coagulopathy is currently unclear.
Aims: Comparing of effect of low-generation anionic and cationic PAMAM on function of fibrinogen and activity of key enzyme of coagulation system of thrombin (Tb).
Methods: Effect of cationic (G1-G3) and anionic (G1.5-G3.5) PAMAM dendrimers on amidolytic and coagulating activities of Tb, thrombin time (TT), prothrombin time (PT), thrombin generation in human plasma; fluorescent-spectrum, zeta-potential, and fibrinogen polymerization by Tb were studied.
Results: Thrombin activity was increased with increasing concentration and generation of cationic dendrimers, anionic inhibited Tb-activity. The cationic dendrimers suppressed Tb-generation in plasma at lower concentrations than anionic. Comparison of cationic and anionic dendrimers with the same number of surface-charged groups showed that cationic dendrimers cause greater changes in generation parameters of thrombogram. G3-dendrimer at concentration of 7 mkM completely suppressed Tb-generation. PT increased with increasing concentration of cationic dendrimers and was independent of anionic dendrimers concentration. Cationic dendrimers elongated PT to greater extent than TT. Studying effect of dendrimers on fluorescent-spectrum, zeta-potential, and fibrinogen polymerization by thrombin showed that cationic dendrimers bind to fibrinogen strongly than anionic dendrimers, and change its conformation and coagulability. Anionic dendrimers didn’t affect on kinetics of fibrinogen polymerization unlike cationic, both type of dendrimers reduced plasma clotting with thrombin.
Conclusions: Compared to anionic (G1.5-G3.5), cationic dendrimers (G1–G3) more strongly suppress the generation of thrombin, alter conformation of fibrinogen and its clotting rate by thrombin in a concentration-dependent manner. The observed effects of cationic PAMAM dendrimers are probably caused by strong electrostatic interactions between positively charged surface of dendrimers and negatively charged sites of thrombin and fibrinogen.
To cite this abstract in AMA style:Mukhametova L, Aisina R, Ivanova E. Influence of Low-generation Polyamidoamine (PAMAM) Dendrimers on Structure and Function of Fibrinogen, Generation, Amidolytic and Coagulating Activity of Thrombin in vitro [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/influence-of-low-generation-polyamidoamine-pamam-dendrimers-on-structure-and-function-of-fibrinogen-generation-amidolytic-and-coagulating-activity-of-thrombin-in-vitro/. Accessed September 16, 2021.
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