Prevention of insulin self-association and surface adsorption.

The self-association of insulin monomers into oligomers and macromolecular aggregates leads to complications in the administration of insulin, both in conventional administration and in the development of long-term insulin delivery systems. These problems are aggravated by the tendency of insulin to adsorb onto the surface of solution containers and infusion devices. Furthermore, with insulin infusion devices, shear rates can be generated which can accelerate the self-association and surface adsorption processes. The effects of urea on shear-induced insulin self-association and surface adsorption were investigated. It was found that the addition of a certain concentration range of urea to insulin solutions greatly reduces both insulin self-association and surface adsorption. Circular dichroic studies established that these concentrations of urea also preserve insulin conformation under high shear rates, where conformations are altered without urea. Higher urea concentrations lead to insulin denaturation and accelerated self-association.