Long-Acting Insulin-Zwitterionic Polymer Conjugate Mitigates Hypoglycemia

Chemistry. 2023 Feb 24;29(12):e202203460. doi: 10.1002/chem.202203460. Epub 2023 Jan 23.

Abstract

Insulin, a main medication to control glycemia of type 1 and advanced type 2 diabetes, faces problems of a short half-life and poor stability during its clinical use. Zwitterionic polymer shows unique properties of antifouling and low immunogenicity. Here, we have synthesized a new insulin-zwitterionic polymer conjugate (INS-PMPC) through grafting-from strategy by controlled radical polymerization. Apart from showing excellent stability upon mechanical agitation, the resulting INS-PMPC conjugate provided over 20 h of glycemic control due to improved pharmacokinetics in diabetic mice with one single subcutaneous injection. Most importantly, this insulin-zwitterionic polymer conjugate significantly decreases the incidence of hypoglycemia.

Keywords: diabetes; hypoglycemia; insulin; insulin-zwitterionic polymer conjugate; storage stability.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental*
  • Diabetes Mellitus, Type 2*
  • Hypoglycemia* / epidemiology
  • Insulin
  • Insulin, Long-Acting
  • Mice
  • Polymers

Substances

  • Insulin, Long-Acting
  • Polymers
  • Insulin