Insulin aggregation in artificial delivery systems

Abstract

Abrupt changes in flow path, motion, elevated temperatures, metal ion contamination, impure insulin formulations, CO2 diffusion, pH drop, dissimilar metal pump components, salt concentration, inappropriate diluents, elevated temperatures, refrigeration temperatures, processing, insulin heterogeneity, and buffering systems have been implicated to a greater or lesser extent in the plugging of insulin delivery devices. Before the rate at which insulin loses its biological activity in delivery systems can be assessed it is obvious that anti-aggregating diluents must be developed and subjected to long-term testing both in vitro and in vivo. Until such stable homogenous formulations are available the knowledge presented in this article will serve to decrease, but not eliminate, the problem of insulin aggregation in delivery systems. Further experiments are in progress and preliminary results [41] provide evidence that the problems cited are not without resolution. In this regard serum apparently contains factor(s) that promote the dissolution of insulin and prevent the formation of peptide aggregates in dilute solutions [41]. Many laboratories are now working to resolve the problem of insulin aggregation in artificial delivery devices. © 1980 Springer-Verlag.