Biocompatibility of Polycations: In Vitro Agglutination and Lysis of Red Blood Cells And In Vivo Toxicity

Abstract

The effects of six polycations were studied in vitro on red blood cells (RBC) and in vivo after intravenous administration. Hemagglutination and hemolysis depended not only on the molar mass and the concentration of these polycations, but also on their chemical nature. The hemagglutination and hemolysis induced by poly(L-lysine), diethylaminoethyldextran, poly(dimethyldiallylammonium) chloride and poly[2-(dimethylamino)ethyl methacrylate] was low to moderate, whereas a severe hemolysis was induced by a partially quaternized poly[thio-1-(N,N-diethyl-aminoethyl)ethylene]. In the case of poly(epsilon-lysine), no significant hemagglutination nor hemolysis was observed. The presence of plasma proteins reduced both agglutination and hemolysis. This protective effect was enhanced when the polycations interacted with plasma proteins before contact with RBC. In the presence of albumin, the behavior depended on the polycation and on the order of addition of the three components of the suspension, namely albumin, polycation and RBC. Depending on the polycation, albumin-polycation complexes were either less active or more active on RBC than the same polycation in protein-free medium. In vivo the studied polycations induced an immediate mortality except poly(epsilon-lysine), which induced a delayed mortality. The minimal dose of polycations inducing immediate mortality paralleled their effect on RBC.