New long-term action insulin formulations obtained using polycations for heparin neutralization

Abstract

Abstract Phenomena that occur between an insulin and four different positively charged polymers (protamine, cationic dextran, chitosan, and poliallylamine derivatives) were studied by dynamic light scattering and fluorescence measurements (using fluorescein-labeled polymers). These processes were compared to the reaction of polycations with heparin that is responsible for the neutralization of anticoagulant activity in blood stream.The nature of polycations interaction with heparin is electrostatic, while the interaction with insulin is more complicated.We observed that the presence of zinc atoms (and its complexing by nitrogen from macromolecules) is critical for insulin suspensions formation and stability. The differences between the nature of these two reactions were revealed. The highly immunogenic action of protamine present in long-acting insulin products makes it reasonable to develop similar systems based on the nonprotein polycations.