Potential Use of Maltosyl‐β‐cyclodextrin for Inhibition of Insulin Self‐association in Aqueous Solution

Abstract

Among the hydrophilic cyclodextrins (CyDs) tested, maltosyl-β-cyclodextrin (G2-β-CyD) significantly restrained the adsorption of insulin to hydrophobic containers and its aggregation. β-CyDs facilitated the permeation of insulin through the ultrafiltration membranes. This increased permeation of insulin was much greater than that by EDTA which is known to prevent insulin self-association by sequestering zinc ions from insulin oligomers. The addition of β-CyDs increased the surface tension of insulin solutions, whereas the addition of EDTA resulted in decrease. In the circular dichroism spectra of insulin, β-CyDs increased the negative intensity around 210 nm and decreased it around 275 nm. In the 1H NMR study, G2-β-CyD changed the signals in the aromatic regions of insulin, particularly B24(Phe) and B26(Tyr), which are involved in the formation of the dimer. The present results suggest that β-CyDs, in particular G2-β-CyD, inhibit the self-association of insulin into oligomers along with their adsorption onto containers by interacting with hydrophobic amino acid residues; hence the CyDs may have the potential to maintain the quality and safety of parenteral formulations of insulin.