4.6 Article

Long-Acting Insulin-Zwitterionic Polymer Conjugate Mitigates Hypoglycemia

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CHEMISTRY-A EUROPEAN JOURNAL
卷 -, 期 -, 页码 -

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WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202203460

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diabetes; hypoglycemia; insulin; insulin-zwitterionic polymer conjugate; storage stability

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By synthesizing the insulin-zwitterionic polymer conjugate (INS-PMPC), the stability and pharmacokinetics of insulin are improved, leading to effective glycemic control and a decreased incidence of hypoglycemia.
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.

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