Investigation of new non-toxic inhibitors of fibril formation and preservatives for insulin preparations its analogues.

Abstract

Insulin and its analogue formulations are the main components in the therapy of insulin-dependent forms of diabetes. Insulin and its analogues can form amyloid-like aggregates during long-term storage and local concentration increases, leading to reduced therapeutic efficacy and potential side effects such as insulin amyloidosis. The aim of this study was to identify and propose new non-toxic inhibitors and preservatives to replace phenol in insulin formulations. The peptide FVNQH and phenol red were studied as promising inhibitors of fibril formation of insulin, lispro, and glargine in vitro using the specific amyloid dye thioflavin T. The peptide FVNQH and phenol red (0.5-1 mg/mL) showed a bacteriostatic effect on the E. coli K-12 strain after 24 h. The fibril-inhibiting and antimicrobial effects of these substances were similar to the effect of phenol at a concentration of 0.5 mg/mL. Thus, the identified inhibitors can potentially replace phenolic components in slowing amyloid aggregation and increase the stability of insulin and its analogues.