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Insulin plays a significant role in diabetes treatment. Although a huge number of insulin-loaded, glucose-responsive nanocarriers have been developed in the past decades, most of them showed lower loading capacity and efficiency due to the weak interaction between insulin and nanocarriers. In this work, a novel insulin-encapsulated glucose-responsive polymeric complex micelles (CM) is devised, showing (i) enhanced insulin loading efficiency owing to the zinc ions chelation by nitrilotriacetic acid (NTA) groups of NTA-functioned glycopolymer and histidine imidazole of insulin, (ii) glucose-triggered pulse release of insulin, and (iii) long stability under physiological conditions. This CM was fabricated by the self-assembly of block copolymer PEG-b-P(Asp-co-AspPBA) and glycopolymer P(Asp-co-AspGA-co-AspNTA), resulting in complex micelles with PEG shell and a cross-linked core composed of phenylboronic acid (PBA)/glucose complexations. Notably, the modified nitrilotriacetic acid (NTA) groups of CM could specifically bind insulin via chelated zinc ions, thus enhance the loading efficacy of insulin, compared to the non-modified CM. The dynamic PBA/glucose complexation core of CM dissociate under the trigger of high glucose concentration (>2 g/L), while being quite stable in low glucose concentration (<2 g/L), as demonstrated by the pulse release of insulin in vitro. Finally, in a murine model of type 1 diabetes, NTA-modified complex micelles loading insulin (NTA-CM-INS) group showed a long hypoglycemic effect which is superior to free insulin in PBS (PBS-INS) group and insulin-loaded complex micelles without NTA modification (CM-INS) group. This long-term effects was benefited from Zn(II) chelation by NTA modified complex micelles and could avoid hypoglycemia caused by the burst release of insulin. Taken together, this constitutes a highly effective way to encapsulate insulin, and release insulin via an on-demand manner for blood glucose control in diabetes.
This article was published in the following journal.
Name: Langmuir : the ACS journal of surfaces and colloids
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A derivative of acetic acid, N(CH2COOH)3. It is a complexing (sequestering) agent that forms stable complexes with Zn2+. (From Miall's Dictionary of Chemistry, 5th ed.)
Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.
A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.
An acetic acid derivative that is a metabolite of TRICHLOROETHYLENE and is formed during chlorine disinfection of drinking water. It has effects on GLUCOSE metabolism, lowers LACTATE, and activates the PYRUVATE DEHYDROGENASE COMPLEX.
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