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Polyethyleneimine-chitosan-octadecanoic acid grafting, preparation and application

A polyethylenimine and chitosan technology, which is applied in the directions of drug combination, genetic material components, and inactive medical preparations, etc. Buffering capacity, improving hydrophobicity, overcoming toxicity issues

Inactive Publication Date: 2011-12-07
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that this material has its unique advantages in terms of cytotoxicity and particle size control of dense DNA products; although key technologies including transferrin ligand modification and polyethylene glycol (PEG) grafting are used, but The problem of low transfection efficiency still exists
The previous research work of the inventor shows that the chitosan stearic acid graft obtained by hydrophobic modification of low molecular weight chitosan can form micelles by self-aggregation in aqueous medium, and the graft micelles have the ability of tumor cells to rapidly The function of ingestion, and has the characteristic of cationic, can close gene drug-plasmid DNA through electrostatic interaction, as a kind of non-viral gene carrier material preparation of gene drug research shows that the use of chitosan stearic acid graft prepared Genetic medicines have high gene expression efficiency compared with genetic medicines themselves, yet their expression efficiency is far lower than that of commercially available liposomes (Lipofectamine TM 2000) Expression of the prepared gene medicine

Method used

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  • Polyethyleneimine-chitosan-octadecanoic acid grafting, preparation and application
  • Polyethyleneimine-chitosan-octadecanoic acid grafting, preparation and application
  • Polyethyleneimine-chitosan-octadecanoic acid grafting, preparation and application

Examples

Experimental program
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Effect test

Embodiment 1

[0023] (1) Synthesis of chitosan-stearic acid graft

[0024] Accurately weigh 5.02g of chitosan whose weight-average molecular weight is 18KDa and the degree of deacetylation is 95%, add 330ml of distilled water after stirring and dissolving, add 8.27g of carbodiimide, stir and dissolve; accurately weigh 1.26g of stearic acid and dissolve in In 170ml ethanol solution, mix the above two solutions, under magnetic stirring, react at a constant temperature of 80°C for 4 hours, then cool down to room temperature, continue to stir for 6 hours until the reaction solution is clear, dialyze with distilled water for 48 hours, freeze-dry the dialysate, and use The remaining stearic acid was removed by washing with absolute ethanol to obtain a chitosan-stearic acid graft; the stearic acid grafting rate of the graft was determined to be 3.46%.

[0025] (2) Synthesis of polyethyleneimine-chitosan-stearic acid graft

[0026]Accurately weigh 0.2 g of chitosan-stearic acid graft and 0.01 g of...

Embodiment 2

[0042] (1) Synthesis of chitosan-stearic acid graft

[0043] Accurately weigh 5.02g of chitosan whose weight-average molecular weight is 18KDa and the degree of deacetylation is 95%, add 330ml of distilled water after stirring and dissolving, add 27.56g of carbodiimide, stir and dissolve; In 170ml ethanol solution, mix the above two solutions, under magnetic stirring, react at a constant temperature of 80°C for 4 hours, then cool down to room temperature, continue to stir for 6 hours until the reaction solution is clear, dialyze with distilled water for 48 hours, freeze-dry the dialysate, and use The remaining stearic acid was removed by washing with absolute ethanol to obtain a chitosan-stearic acid graft; the stearic acid grafting rate of the graft was determined to be 20.7%.

[0044] (2) Synthesis of polyethyleneimine-chitosan-stearic acid graft

[0045] Accurately weigh 0.2 g of chitosan-stearic acid graft and 0.01 g of sodium periodate. Dissolve in 20ml of acetic acid b...

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Abstract

The invention provides a polyethyleneimine-chitosan-octadecanoic acid grafting, which is macromolecular substance, wherein parts of free amino groups on a chitosan chain are replaced by stearic acid or polyethyleneimine of which the weight-average molecular weight is 800Da. In the invention, on the basis of chitosan-octadecanoic acid grafting with the function of rapid cell absorbing, the polyethyleneimine with small molecular weight is modified, thereby improving the hydrophobicity of the original chitosan-octadecanoic acid grafting molecular structure, substantially increasing amino, improving the ion buffer capacity of molecular, and overcoming the toxicity of the polyethyleneimine. By the combination of rapid cell absorbing of the chitosan-octadecanoic acid grafting and the strong proton sponge effect of the polyethyleneimine, the invention can be applied to preparing the gene medicine so as to realize the high-level expression of the gene medicine and the effectiveness of oncogene therapy.

Description

technical field [0001] The invention relates to a novel cationic ternary graft and its synthesis method and application, specifically polyethyleneimine-chitosan-stearic acid graft and its synthesis method, and polyethyleneimine-chitosan-stearic acid The graft is used as a non-viral gene carrier in the preparation of gene medicine. Background technique [0002] Gene therapy refers to the transfer of exogenous genes into the diseased cells, and by restoring or increasing gene expression to correct the structural or functional disorder of the human gene, prevent the progression of the disease, kill the diseased cells, and inhibit the genetic material of the exogenous pathogen. copy, so as to achieve the purpose of treatment. Vectors that successfully release foreign genes in vivo are mainly divided into two categories: viral and non-viral vectors. Among them, the modified viral vector has higher transfection efficiency and is the main means of gene therapy. Viral vectors inc...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08G81/00C08B37/08A61K48/00A61K47/48A61P35/00A61K47/36
Inventor 胡富强杜永忠袁弘
Owner ZHEJIANG UNIV
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