Differential Effects of Cyclodextrin Derivatives on Aggregation and Thermal Behavior of Insulin

Abstract

Maltosyl-β-cyclodextrin (G2-β-CyD) suppressed the aggregation of insulin in a neutral solution, while the sulfate of α-CyD (S-α-CyD) accelerated the aggregation. On the other hand, the sulfobutyl ether of β-CyD (SBE-β-CyD) showed differential effects on the insulin aggregation, depending on the degree of substitution; i.e. the inhibition at relatively low substitution and acceleration at higher substitution. Differential scanning calorimetric (DSC) studies indicate that the self-association of insulin stabilized the native conformation of the peptide, as indicated by an increase in the mean unfolding temperature (Tm). G2-β-CyD and SBE-β-CyD decreased the Tm value of insulin oligomers, while S-α-CyD increased the Tm value. These results suggest that a proper use of the CyD derivatives is effective in designing rapid and long-acting insulin preparations.