Reduction-sensitive polyethyleneimine derivative, its preparation method and application

A polyethylenimine, sensitive technology, applied in the field of biomedical materials, to achieve the effect of improving stability, improving hydrophilic-lipophilic balance, and increasing cell uptake

Active Publication Date: 2019-12-13
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] According to patent inquiries and literature searches, there are no reports at home and abroad that the two methods of hydrophobic modification and cross-linking agent cross-linking are simultaneously applied to modify polyethyleneimine to balance its transfection activity and toxicity.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Reduction-sensitive polyethyleneimine derivative, its preparation method and application
  • Reduction-sensitive polyethyleneimine derivative, its preparation method and application
  • Reduction-sensitive polyethyleneimine derivative, its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0047] Preparation Example 1: Preparation of linear PEI with a molecular weight of 2200 (lPEI2200)

[0048] At present, there is no commercially available linear lPEI2200, so we use poly(2-ethyl-2-oxazoline) PEOZ with a molecular weight of 5000 as a precursor, and remove its propionyl group by acid hydrolysis to obtain lPEI2200 with a molecular weight of 2200 , the preparation method is as follows: Weigh about 3 g of poly(2‐ethyl‐2‐oxazoline) PEOZ with a molecular weight of 5000 and place it in a 250 ml round bottom flask, add 120 ml of 24% (wt / vol) hydrochloric acid solution, and heat at 110 °C The oil bath was refluxed for 96 hours, and then the reaction was stopped. After the reaction system was cooled to room temperature, the reaction system was filtered under reduced pressure on a Buchner funnel to obtain a white filter cake, which was air-dried at room temperature to obtain lPEI2200.

preparation example 2

[0049] Preparation Example 2: Preparation of linear PEI with a molecular weight of 22000 (lPEI22000)

[0050] We used poly(2-ethyl-2-oxazoline) PEOZ with a molecular weight of 50,000 as a precursor, and removed its propionyl group by acid hydrolysis to obtain lPEI22000 with a molecular weight of 22,000. The preparation method was as follows: About 3g of poly(2‐ethyl‐2‐oxazoline) PEOZ was placed in a 250ml round bottom flask, 120ml of 24% (wt / vol) hydrochloric acid solution was added, and the oil bath was refluxed at 110°C for 96h, then the reaction was terminated, and the reaction The system was cooled to room temperature, and the reaction system was filtered with Buchner funnel under reduced pressure to obtain a white filter cake, which was air-dried at room temperature to obtain lPEI22000.

preparation example 3

[0051] Preparation Example 3: Low molecular weight polyethyleneimine grafted with aliphatic hydrocarbon group (bPEI1800-C 12 -12.5) Preparation of

[0052] (1) Weigh 1 g of branched polyethyleneimine (bPEI1800) with a molecular weight of 1800, dissolve it in 100 ml of a mixed solvent of dichloromethane and methanol (the volume ratio of the two is 95:5), stir and dissolve at 30 °C ;

[0053] (2) Weigh 0.7245g of 1-bromododecane and dissolve it in 50ml 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 10ml / h. In the amine solution, at 40°C, in the dark for 24 hours;

[0054] (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 ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides a reducing sensitive polyethyleneimine derivative as well as a preparation method and application thereof. The preparation method of the reducing sensitive polyethyleneimine derivative comprises the following steps: carrying out hydrophobic modification on polyethyleneimine by adopting aliphatic hydrocarbon, and further carrying out disulphide bond crosslinking, so that a biodegradable polyethyleneimine with certain hydrophobicity and reducing sensitivity (a disulphide bond can be reduced and broken in a tumour cell) is obtained. The polyethyleneimine derivative provided by the invention has hydrophobicity, affinity between a material and a biological membrane is improved, and the cell uptake efficiency can be improved; the disulphide bond in a molecule enables the material to have reducing environment responsibility and biodegradability, the nucleic acid delivery efficiency is high, and the safety is good. The reducing sensitive polyethyleneimine derivative provided by the invention has the advantages that the transfection efficiency of delivered DNA and the target gene silencing efficiency of delivered siRNA are far higher than those of lipofectamine2000, and the toxicity is greatly lower than that of lipofectamine2000, so that the reducing sensitive polyethyleneimine derivative is a high-efficiency and low-toxicity nucleic acid delivery carrier and has a 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 reduction-sensitive polyethyleneimine derivative, a preparation method and application thereof. 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. Among many nucleic acid delivery vehicles, polyethyleneimine (PEI) has been widely studied due to its high charge density (effectively condensing nucleic acid) and unique intracellular transport mechanism (intracellular lysosome escape). Branched PEI with a molecular weight of 25KDa and In vivo jetPEI TM (linear PEI with a molecular weight of 22 KDa) is considered to be the gold standard for in vitro nucleic acid delivery and in vivo nucleic acid delivery, respectively. Howe...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): C08G81/00C08G73/02C12N15/63
Inventor 高钟镐柳珊黄伟杨飞飞金明姬
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap