To improve the understanding of the physicochemical behavior of polyplexes (DNA-polycation complexes) and to avoid the complexity of blood, the formation and stability of polyelectrolyte complexes of degradable polycations and polyanions, we previously studied under pH, temperature, and ionic strength typical of human blood. In this study, the investigation is extended to polycationic macromolecules added into mixtures of polyanions selected to mimic polyanionic species present in blood. The poly(l-lysine) polycation was added to binary mixtures of degradable polyanions with different charge densities and hydrophobicity. The polyanions were poly(l-lysine citramide imide), poly(l-lysine citramide), and poly(l-lysine citramide) partially esterified with heptyl groups. We found selectivity and fractionation in the molar mass, which depended on the structural characteristics of the polyanions. The affinity of polycationic poly(l-lysine) macromolecules to polyanions increased in the following order: poly(l-lysine citramide imide) < poly(l-lysine citramide) < hydrophobized poly(l-lysine citramide). These data complements the previous information with respect to the possibility of polyplex destabilization and/or the interactions of polycationic macromolecules in excess with the polyanionic species present in blood, depending on the physicochemical characteristics of the polyplex, the excess polycation, and blood elements.
