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Nitrilotriacetic Acid-Functionalized Glucose-Responsive Complex Micelles for the Efficient Encapsulation and Self-Regulated Release of Insulin
- Source :
- Langmuir : the ACS journal of surfaces and colloids. 34(40)
- Publication Year :
- 2018
-
Abstract
- Insulin plays a significant role in diabetes treatment. Although a huge number of insulin-loaded, glucose-responsive nanocarriers have been developed in past decades, most of them showed a 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 micelle (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 the histidine imidazole of insulin, (ii) the 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 a 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 enhancing the loading efficacy of insulin compared to that of nonmodified CM. The dynamic PBA/glucose complexation core of CM dissociates under the trigger of high glucose concentration (2 g/L) while being quite stable in low glucose concentrations (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 an insulin (NTA-CM-INS) group exhibited a long hypoglycemic effect which is superior to that of free insulin in the PBS (PBS-INS) group and insulin-loaded complex micelles without an NTA modification (CM-INS) group. This long-term effect 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.
- Subjects :
- Nitrilotriacetic Acid
Glycopolymer
02 engineering and technology
010402 general chemistry
01 natural sciences
Micelle
Polyethylene Glycols
chemistry.chemical_compound
Mice
PEG ratio
Electrochemistry
Animals
Insulin
General Materials Science
Chelation
Phenylboronic acid
Spectroscopy
Histidine
Micelles
Chelating Agents
Drug Carriers
Nitrilotriacetic acid
Surfaces and Interfaces
021001 nanoscience & nanotechnology
Condensed Matter Physics
Boronic Acids
0104 chemical sciences
Drug Liberation
Zinc
Diabetes Mellitus, Type 1
Glucose
chemistry
NIH 3T3 Cells
Nanocarriers
0210 nano-technology
Peptides
Nuclear chemistry
Subjects
Details
- ISSN :
- 15205827
- Volume :
- 34
- Issue :
- 40
- Database :
- OpenAIRE
- Journal :
- Langmuir : the ACS journal of surfaces and colloids
- Accession number :
- edsair.doi.dedup.....5963fed8e1c645e756f8aaaf232c86de