Interactions between red blood cells and a lethal, partly quaternized tertiary polyamine

Partially quaternized poly[thio-1-(N,N-diethyl-aminomethyl) ethylene]s, Q-P (TDAE)(x) with x indicating the percentage of quaternized subunits, have be en proposed as potential carriers for drugs insoluble in water. However the se cationic polyelectrolytes form emboli upon intravenous administration. I n order to study the mechanism, Q-P(TDAE)(11) was incubated in vitro with r ed blood cells (RBCs) suspended in various aqueous media such as autologous plasma, autologous serum, albumin dissolved in phosphate buffer, plasma-se rum mixtures and Tris buffer. The deformability of the RBC membrane studied by viscometry was not affected by the polycation. Q-P(TDAE)(11)-induced he magglutination was studied by optical microscopy. It depended on the polyme r concentration and on the presence of plasma proteins. As ghosts were form ed in some cases, hemolysis was investigated by measuring potassium and hem oglobin released from RBCs. Fibrinogen and serum proteins, except albumin, protected RBCs from hemolysis. Moreover the order of addition of the suspen sion components modulated dramatically the Q-P(TDAE)(11)-induced hemolysis. Addition of Q-P(TDAE)(11) to whole blood caused hemolysis whereas addition of the polymer to plasma prior to contact with RBCs did not affect the cel l integrity. In contrast, addition of the polymer to RBCs suspended in albu min solution caused greater hemolysis than the addition to whole blood, and the contact between Q-P(TDAE)(11) and albumin prior to RBC addition still enhanced cell lysis. Two conclusions can be drawn from these observations: (i) Q-P(TDAE)(11) induces both hemagglutination, probably through electrost atic interaction, and hemolysis, because Q-P(TDAE)(11) disrupted the RBC li pid bilayer; (ii) proteins can decrease or increase the deleterious effects of Q-P(TDAE)(11) on RBCs. (C) 2000 Elsevier Science B.V. All rights reserv ed.