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

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Hematology

Background:

• Partially quaternized poly[thio-1-(N,N-diethyl-aminomethyl) ethylene]s (Q-P(TDAE)(x)) are investigated as potential carriers for hydrophobic drugs.
• These cationic polyelectrolytes have shown a propensity to form emboli during intravenous administration, necessitating a deeper understanding of their interaction with biological systems.

Purpose of the Study:

• To elucidate the mechanism by which Q-P(TDAE)(11) interacts with red blood cells (RBCs).
• To investigate the influence of various aqueous media and plasma proteins on Q-P(TDAE)(11)-induced hemagglutination and hemolysis.

Main Methods:

• In vitro incubation of Q-P(TDAE)(11) with RBCs in diverse media (plasma, serum, albumin, buffers).
• Assessment of RBC membrane deformability using viscometry.
• Microscopic observation of Q-P(TDAE)(11)-induced hemagglutination.
• Quantification of hemolysis by measuring released potassium and hemoglobin.

Main Results:

• RBC deformability remained unaffected by Q-P(TDAE)(11).
• Hemagglutination was dependent on polymer concentration and the presence of plasma proteins.
• Fibrinogen and serum proteins (excluding albumin) offered protection against hemolysis.
• The order of component addition critically modulated hemolysis, with Q-P(TDAE)(11) added to whole blood causing lysis, but not when added to plasma first.
• Pre-incubation of Q-P(TDAE)(11) with albumin enhanced RBC lysis.

Conclusions:

• Q-P(TDAE)(11) induces hemagglutination via electrostatic interactions and hemolysis by disrupting the RBC lipid bilayer.
• Plasma proteins can either mitigate or exacerbate the adverse effects of Q-P(TDAE)(11) on RBCs, depending on the specific protein and experimental conditions.