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Preparation method and application of redox-responsive hyperbranched skeleton

A skeleton and reaction technology, applied in the field of preparation of redox-responsive hyperbranched skeletons, can solve the problems of difficulty in gene release and poor solubility in cells, and achieve enhanced control release ability, improved cell uptake ability, safe and efficient gene delivery effect

Active Publication Date: 2019-07-09
DALIAN NATIONALITIES UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Conjugate chitin at the end of hyperbranched polymers to prepare hyperbranched polychitin, which is expected to solve the problems of poor solubility of traditional chitin gene carriers and difficulty in intracellular gene release due to chain entanglement

Method used

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  • Preparation method and application of redox-responsive hyperbranched skeleton
  • Preparation method and application of redox-responsive hyperbranched skeleton
  • Preparation method and application of redox-responsive hyperbranched skeleton

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Dissolve 0.012g of 3,3'-dithiodipropionate bis(N-hydroxysuccinimide) in 10mL of dimethyl sulfoxide, slowly add 0.5g of polyethyleneimine (MW=1800Da) dropwise React in the above solution at room temperature for 3 h, transfer the reaction solution to a dialysis bag with a molecular weight cut-off of 1000 Da, perform dialysis with deionized water, and then freeze-dry to obtain a solid redox-responsive hyperbranched polymer.

Embodiment 2

[0026] Dissolve 0.4g of bis(N-hydroxysuccinimide) suberate in 10mL of dimethyl sulfoxide, and dissolve another 0.5g of chitin (MW=1000Da) in 20mL of ultrapure water, and slowly Add dropwise (dropping for about 30min), take 0.05g of the redox-responsive hyperbranched polymer skeleton prepared in Example 1 and dissolve it in 20mL of ultrapure water, and then slowly add this solution dropwise to the above solution (dropping for about 30min) , stirred and reacted at room temperature for 4 hours, transferred the reaction solution to a dialysis bag with a molecular weight cut-off of 1000 Da, dialyzed with deionized water, and then freeze-dried to prepare redox-responsive hyperbranched polychitosan ss-HBPC.

Embodiment 3

[0028] Dissolve 0.012g of 3,3'-dithiodipropionate bis(N-hydroxysuccinimide) in 10mL of dimethyl sulfoxide, slowly add 0.5g of polyethyleneimine (MW=600Da) dropwise React in the above solution at room temperature for 3 hours, transfer the reaction solution to a dialysis bag with a molecular weight cut-off of 1000 Da, perform dialysis with deionized water, and freeze-dry to obtain a solid redox-responsive hyperbranched polymer.

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Abstract

The invention provides a preparation method and application of a redox-responsive hyperbranched skeleton. The hyperbranched skeleton having a divergent structure is designed by performing crosslinkingon a disulfide bond-containing bifunctional reagent and a low-molecular-weight hyperbranched polymer; and the hyperbranched skeleton is different from a conventional dendritic molecule or a hierarchical bifurcation structure. The periphery of the disulfide bond crosslinked hyperbranched skeleton designed by the invention can graft chitosan to prepare hyperbranched chitosan with redox response, and structural limitation of original linear chitosan is overcome; and the environment-responsive hyperbranched chitosan prepared by adopting the hyperbranched skeleton provided by the invention exhibits excellent biocompatibility and high-efficiency gene delivery performance, and has broad application prospects in the fields of gene therapy and gene editing.

Description

technical field [0001] The invention relates to a preparation method of a redox responsive hyperbranched skeleton, in particular to a redox responsive hyperbranched chitin conjugate with pH responsiveness and its application in the field of gene drug delivery, belonging to drug delivery Preparation methods and technologies of new drug carriers in the field. Background technique [0002] Gene therapy introduces foreign genes into target cells to repair defective genes that cause diseases or inhibit harmful genes that cause diseases, so as to restore the body to normal functions and achieve the purpose of treating diseases [1. Chinese invention patent, authorization number ZL201010601008. 5. The name of the invention is: glutathione-modified chitosan copolymer used as a non-viral gene carrier material and its preparation and application]. Gene therapy technology provides new treatment methods for diseases that cannot be cured by conventional medical means. Gene editing refer...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08J3/24C08L5/08C08L79/02C08L77/04C08B37/08A61K47/36A61K48/00
CPCC08J3/24C08J3/246C08B37/003A61K47/36A61K48/0041C08J2305/08C08J2479/02C08J2379/02C08J2377/04C08J2477/04
Inventor 张树彪陈会英范雪枫蓝浩铭马羽
Owner DALIAN NATIONALITIES UNIVERSITY
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