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Preparation of sugar-responsive functionalized nano-composite micelle and application of sugar-responsive functionalized nano-composite micelle in insulin delivery

A nano-composite glue and functionalization technology, applied in the field of nano-biomedical materials, can solve the problems that have not been well solved, and the poor stability of insulin aggregation, so as to achieve the effect of protecting the structure, realizing the release of glucose stimulation response, and inhibiting aggregation

Active Publication Date: 2021-06-01
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the problems of easy aggregation and poor stability of insulin have not been well resolved

Method used

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  • Preparation of sugar-responsive functionalized nano-composite micelle and application of sugar-responsive functionalized nano-composite micelle in insulin delivery
  • Preparation of sugar-responsive functionalized nano-composite micelle and application of sugar-responsive functionalized nano-composite micelle in insulin delivery
  • Preparation of sugar-responsive functionalized nano-composite micelle and application of sugar-responsive functionalized nano-composite micelle in insulin delivery

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] A method for preparing sugar-responsive functionalized nanocomposite micelles, the method steps and related evaluations are as follows:

[0039] 1) Synthesis of PCL-b-PEG

[0040] Add 0.1 mmol PEG-OH that has been vacuum-dried in advance and 10 mmol ε-CL that has been distilled under reduced pressure to a 50 mL dry Schlenk bottle and mix, dissolve with 7 mL redistilled anhydrous toluene, and then add a drop of catalyst stannous octoate (Sn (October) 2). After three repetitions of freezing with liquid nitrogen—vacuumizing—thawing, react in an oil bath at 108-112° C. for 12 hours under the protection of nitrogen. After the reaction is completed, add an appropriate amount of dichloromethane to dilute, and then precipitate in ten times the volume of glacial ether. Put it in the refrigerator and let it stand overnight, then filter it with suction, wash it, and vacuum-dry it to obtain a white flocculent solid that is PCL-b-PEG.

[0041] 2) Synthesis of PCL-NHBoc;

[0042...

Embodiment 2

[0064] Example 2: Application of sugar-responsive functionalized polymer micelles.

[0065] An application of sugar-responsive functionalized nanocomposite micelles, the method steps and related evaluations are as follows:

[0066] 1) Research on the interaction between compound micelles and insulin;

[0067] The interaction of micelles with insulin was studied by FRET effect. The principle is that when the distance between the donor and the acceptor is close enough (generally less than 10nm), after the fluorescent donor is excited, the energy in the excited state of the donor will be non-radioactively transferred to the acceptor, which induces the excitation of the fluorescent acceptor, and the energy transfer occurs. In this study, RhB was labeled on the hydrophobic domain of complex micelles, and 1 mL of the micelles was mixed with 0.2 mL FITC-labeled insulin at 37 °C for 2 h, and the fluorescence spectra were recorded (FITC is the donor, RhB is the acceptor , excitation ...

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Abstract

The invention relates to preparation of a sugar-responsive functionalized nano-composite micelle and application of the sugar-responsive functionalized nano-composite micelle in insulin delivery. Three block copolymers, namely PCL-b-PEG, PCL-b-P (Asp-co-AspPBA) and PCL-b-P (Asp-co-AspNTA), are self-assembled to form the composite micelle which takes PCL as a core and takes PEG / PAPBA / PANTA as a mixed shell layer. The NTA-modified chain segment PANTA is combined with Zn<2+> through chelation, and then insulin is captured by utilizing the coordination effect of Zn<2+> and histidine on an insulin B chain. The segment PAPBA with PBA forms a hydrophobic area under neutral or sugar-free conditions. The captured insulin is incubated for a period of time and then can be bound to a hydrophobic area, and the insulin is loaded to the composite micelle through the synergistic effect of coordination and hydrophobicity. Under the high-glucose condition, the hydrophobic area is changed from hydrophobic to hydrophilic, the acting force between the composite micelle and insulin is weakened, and the insulin is released to play a role.

Description

technical field [0001] The invention belongs to the field of nano biomedical materials. The coordination domain and the hydrophobic domain on the surface of the compound micelles are used to load insulin, and undergo a hydrophilic-hydrophobic transition in a high-sugar environment to release insulin responsively to sugar. Background technique [0002] Diabetes mellitus is a chronic disease characterized by disorders of glucose metabolism, resulting in elevated blood sugar in the body due to dysfunction of insulin secretion or inability to effectively use insulin. In recent years, the number of diabetes cases in the world has increased rapidly, and it is accompanied by a trend of younger age. It is one of the three major killers that endanger human health. Therefore, the treatment of diabetes is an urgent problem to be solved. At present, insulin, as the key hormone regulating glucose metabolism in the human body, is a protein drug clinically used to treat type 1 diabetes, an...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/59A61K47/60A61K38/28A61P3/10
CPCA61K47/6907A61K47/593A61K47/60A61K47/59A61K38/28A61P3/10Y02P20/55
Inventor 史林启张艳丽李畅刘阳马如江安英丽
Owner NANKAI UNIV
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