Nanocomposites PAMAM derivatives with antitrombogenic activity and hemocompatibility

E.F. Durán, L.A. Guzmán, A. John, E.J. Fuentes, F.M. Nachtigall, I.F. Palomo, L.S. Santos
Fraunhofer Chile Research, CL

Keywords: PAMAM, PAMAM derivatives, thrombogenicity, hemocompatibility


We synthesized derivatives of PAMAM G4 and G5 and their hemocompatibility and thrombogenicity was studied. We demonstrate that PAMAM G4, G5 and derivatives have high hemocompatibility in relation to the observed morphology and hemolysis of red blood cells. However, PAMAM G5 and derivatives showed high thrombogenicity activity with the exception of Cafestol-G5-PEG-G5-Cafestol (PAMAM G5-PEG-Cafestol), which also present a significant inhibition of platelet endothelial adhesion (matrix of collagen and fibrinogen). PAMAM G4 alone exhibits good inhibition of the platelet endothelial adhesion; on the other hand, the G4 derivatives, arginine and lysine act as potent inhibitors of platelet aggregation induced by 8 μM of ADP. However, PAMAM G4 alone showed over a 10% of hemolysis of red blood cells. We can conclude, that the range of PAMAM derivatives synthesized, PAMAM G5-PEG-Cafestol, Lys-G4 and Arg-G4 have significant antithrombotic activity coupled with almost no cytotoxicity in red blood cells, emerging them as good candidates for future in vivo studies of thrombogenicity induced by either endothelial damage or thrombosis in situ, where they act as carriers and antithrombotic drug delivery, enhancing the biological effect of these.