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Nitrilotriacetic Acid Functionalized Glucose-Responsive Complex Micelles for Efficient Encapsulation and Self-Regulated Release of Insulin.

08:00 EDT 13th September 2018 | BioPortfolio

Summary of "Nitrilotriacetic Acid Functionalized Glucose-Responsive Complex Micelles for Efficient Encapsulation and Self-Regulated Release of Insulin."

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.

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This article was published in the following journal.

Name: Langmuir : the ACS journal of surfaces and colloids
ISSN: 1520-5827
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