Influence of cyclodextrins on the stability of the peptide salmon calcitonin in aqueous solution

The influence of beta-cyclodextrin (betaCD), and various betaCD derivatives, on both the chemical and the physical stability of the polypeptide hormone salmon calcitonin (sCT) in aqueous solutions was investigated at elevated temperature (55 degrees C). Also, the influence of various betaCD derivatives on the enzymatic degradaton of sCT was evaluated. At pH 6, the effect of CDs on the chemical stability of sCT was negligible at CD concentrations below 5% (w/v). The only exception was the negatively charged carboxymethyl-betaCD (CMbetaCD), which increased sCT stability. The charged CDs, i.e. 2-hydroxytrimethylammonio-propyl-betaCD (TMAbetaCD) and CMbetaCD, promoted degradation in concentrated solutions of sCT at pH 6. 2-Hydroxypropyl-betaCD (HPbetaCD) and randomly methylated betaCD (RMbetaCD) not only inhibited aggregation, they also solubilised dimers formed in the test solutions, thereby increasing the physical stability. All the CDs tested accelerated the alpha-chymotryptic degradation of sCT. Maltosyl-betaCD (G(2)betaCD), HPbetaCD and RMbetaCD showed an inhibition of leucine aminopeptidic and tryptic degradation.