Aliphatic group-grafted low molecular weight polyethyleneimine as well as preparation method and application of polyethyleneimine

A polyethyleneimine, low molecular weight technology, applied in the field of biomedical materials, can solve the problems of high price, high toxicity, and no aliphatic hydrocarbon group grafted small molecular weight branched PEI reported in literature, etc., and achieves increased affinity and low toxicity. , the effect of improving stability

Inactive Publication Date: 2014-12-24
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, the commercially available transfection reagent lipofectamine2000, which is relatively mature, has high transfection efficiency, but it is highly toxic and expensive. Therefore, it is urgent to develop efficient, safe and economical transfection reagents.
[0007] According to patent inquiries and literature searches, there is no literature report on the use of aliphatic hydrocarbon groups grafted with small molecular weight branched PEI.

Method used

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  • Aliphatic group-grafted low molecular weight polyethyleneimine as well as preparation method and application of polyethyleneimine
  • Aliphatic group-grafted low molecular weight polyethyleneimine as well as preparation method and application of polyethyleneimine
  • Aliphatic group-grafted low molecular weight polyethyleneimine as well as preparation method and application of polyethyleneimine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Embodiment 1: Preparation of low molecular weight polyethyleneimine grafted with aliphatic hydrocarbon group

[0040] (1) Weigh branched polyethyleneimine (bPEI) with a molecular weight of 1800 1800 ) 1g, dissolved in 100ml of a mixed solvent of dichloromethane and methanol (the volume ratio of the two is 95:5), stirred and dissolved at 30°C;

[0041] (2) Weigh 1.1430 g of 1-bromododecane and dissolve it in 50 ml of a mixed solvent of dichloromethane and methanol (95:5 by volume), and add it dropwise to the above-mentioned polyethylene glycol at a rate of 10 ml / h. In the amine solution, at 40°C, in the dark for 24 hours;

[0042] (3) The obtained mixed solution was spin-dried by rotary evaporation to obtain a light yellow semi-solid paste. The semi-solid paste was suspended in 6ml of distilled water, and then the dialysis bag with a molecular weight cut-off of 1000 was first used in 40% Dialyzed in ethanol solution for 6 times, and then dialyzed in deionized water for...

Embodiment 2

[0044] Embodiment 2: Preparation of low molecular weight polyethyleneimine grafted with aliphatic hydrocarbon group

[0045] (1) Weigh branched polyethyleneimine (bPEI) with a molecular weight of 1800 1800 ) 1g, dissolved in 100ml of a mixed solvent of dichloromethane and methanol (the volume ratio of the two is 90:10), stirred and dissolved at 40°C;

[0046] (2) Weigh 3.037g of 1-bromohexane and dissolve it in 50ml of a mixed solvent of dichloromethane and methanol (the volume ratio of the two is 90:10), and add it dropwise to the above polyethyleneimine solution at a rate of 50ml / h , at 40°C, protected from light for 24 hours;

[0047] (3) The obtained mixed solution was spin-dried by rotary evaporation to obtain an off-white semi-solid paste, which was suspended in 10ml of distilled water, and then used in a dialysis bag with a molecular weight cut-off of 1000 in 50% Dialyzed in ethanol solution for 5 times, then dialyzed in deionized water for 48 hours, and freeze-dried ...

Embodiment 3

[0048] Embodiment 3: the preparation of the low molecular weight polyethyleneimine of aliphatic hydrocarbon group grafting

[0049] (1) Weigh branched polyethyleneimine (bPEI) with a molecular weight of 600 600 ) 1g, dissolved in 100ml of a mixed solvent of dichloromethane and methanol (the volume ratio of the two is 99:1), stirred and dissolved at 40°C;

[0050] (2) Weigh 5.159g of 1-bromodecane and dissolve it in 50ml of a mixed solvent of dichloromethane and methanol (the volume ratio of the two is 99:1), and add it dropwise to the above polyethyleneimine solution at a rate of 15ml / h , at 40°C, protected from light for 12 hours;

[0051] (3) The obtained mixed solution was spin-dried by rotary evaporation to obtain a gray semi-solid paste, which was suspended in 10ml of distilled water, and then used in a dialysis bag with a molecular weight cut-off of 500 in 60% Dialyzed in ethanol solution for 6 times, then dialyzed in deionized water for 24 hours, and freeze-dried for ...

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Abstract

The invention provides aliphatic group-grafted low molecular weight polyethyleneimine as well as a preparation method and application of the polyethyleneimine. An aliphatic group is grafted on an amino group of the low molecular weight polyethyleneimine by virtue of a one-step synthesis method, composite particles formed by compounding the aliphatic group-grafted low molecular weight polyethyleneimine and nucleic acid can be self-assembled in an aqueous solution to form a micelle-shaped structure, so that the stability is greatly improved; the affinity between the material and cells is increased by virtue of lipotropy of the grafted material, so that relatively low cell toxicity of the low molecular weight polyethyleneimine is kept while the delivery efficiency of the nucleic acid is improved. Besides, the highest transfection efficiency of the delivered plasmid DNA in the presence of blood serum and the target gene silencing efficiency of the delivered siRNA by virtue of the aliphatic group-grafted low molecular weight polyethyleneimine provided by the invention are equal to those of commercially available lipofectamine 2000; and moreover, obvious cell toxicity is avoided, and thus, the aliphatic group-grafted low molecular weight polyethyleneimine is an efficient low-toxicity nucleic acid delivery carrier and has a relatively good application prospect.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and relates to a polymer carrier material, in particular to a low-molecular-weight polyethyleneimine derivative grafted with aliphatic hydrocarbon group, its preparation method and application. Background technique [0002] Nucleic acid therapy is a powerful tool for the treatment of various congenital and acquired diseases, but how to achieve safe and effective in vivo delivery of nucleic acid drugs is a major technical bottleneck of nucleic acid therapy. Currently commonly used nucleic acid delivery vectors can be divided into recombinant viral vectors and artificially synthesized vectors (non-viral vectors). Viral vectors have high transfection efficiency, but are difficult to prepare and purify, have small capacity to carry nucleic acid, and are potentially pathogenic. Non-viral vectors are considered to be more ideal nucleic acid drug delivery vehicles than viral vectors. [0003] Non-v...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G73/04A61K47/34A61K48/00C12N15/63C12N15/87
Inventor 高钟稿黄伟柳珊杨飞飞金明姬
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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