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Preparations of cationic polymer modified by steroid hormone and gene composite thereof

A technology of cationic polymers and steroid hormones, applied in gene therapy, medical preparations of non-effective ingredients, genetic material components, etc., can solve the problem of low transfection efficiency of cationic polymer cells, inability to effectively pass through nuclear pore complexes, and polymerization Overcoming the problems of slow progress of biological gene carriers, etc., to overcome the effects of small load of exogenous genes, reliable application, and simple preparation methods

Inactive Publication Date: 2012-01-25
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, compared with viral vectors, the cell transfection efficiency of cationic polymers is much lower, and the main limiting step is the nuclear membrane barrier in cells
The nuclear pore complex on the surface of the nucleus has extremely strict control on the particles entering and leaving the nucleus, and most gene transfer carriers cannot effectively pass through the nuclear pore complex
[0007] Regrettably, research on polymeric gene carriers for nuclear-targeted delivery is still progressing slowly

Method used

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  • Preparations of cationic polymer modified by steroid hormone and gene composite thereof
  • Preparations of cationic polymer modified by steroid hormone and gene composite thereof
  • Preparations of cationic polymer modified by steroid hormone and gene composite thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] It should be fully explained that the following examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. For example, the polyethyleneimine described in the present invention can also be a derivative of polyethyleneimine, and its molecular weight should not be limited to the molecular weight used. The type of steroid hormones used as targeting molecules is not limited to the range adopted in the examples, and should have a wider range of selection scales, all of which should not be a limitation to the claims. Synthesis of the polyethyleneimine polymer modified by embodiment 1 dexamethasone

[0058] Take 0.1g dexamethasone, dissolve it in 20ml absolute ethanol, add a certain amount of H 2 SO 4 solution, adjust the pH to about 3, in N 2 Add potassium periodate solution under protection to mix completely, react at room temperature for 24 hours, remove the solvent by rotary evaporation to obtain a white ...

Embodiment 2

[0060] Synthesis of the polyethylenimine polymer modified by embodiment 2 prednisolone

[0061] Take 0.1g prednisolone, dissolve it in 20ml absolute ethanol, add a certain amount of H 2 SO4 solution, adjust the pH to about 3, in N 2 Add potassium periodate solution under protection to make it completely mixed, react at room temperature for 24 hours, remove the solvent by rotary evaporation to obtain a white precipitate, add 0.05mol / L NaOH solution to dissolve the precipitate, adjust the pH of the system to 2 with HCl, and place it at room temperature for 2 hours, 4 overnight at ℃, filter with suction, wash the precipitate with water, P 2 o 5 Vacuum drying to obtain prednisolone oxide (O-Pon). Dissolve PEI (Sigma, MW=25000) and the intermediate prednisolone oxide in N, N-dimethylformamide (DMF), mix the two solutions and put them in an ice bath, take an appropriate amount of EDC and dissolve them in In DMF, it was slowly added dropwise to the mixed solution of PEI and O-Pon...

Embodiment 3

[0062] Synthesis of the chitosan amino derivative polymer modified by embodiment 3 dexamethasone

[0063] Take 0.1g dexamethasone, dissolve it in 20ml absolute ethanol, add a certain amount of H 2 SO4 solution, adjust the pH to about 3, in N 2 Add potassium periodate solution under protection to mix completely, react at room temperature for 24 hours, remove the solvent by rotary evaporation to obtain a white precipitate, add 0.05mol / L NaOH solution to dissolve the precipitate, adjust the pH of the system to 2 with HCl, place at room temperature for 2 hours, 4°C Overnight, filter with suction, wash the precipitate with water, P 2 o 5 The oxidized dexamethasone (O-Dex) was obtained by vacuum drying. Chitosan amino derivatives (chitosan comes from Yuhuan County Marine Biochemical Co., Ltd., MW = 10000, chitosan amino derivatives are self-made products) and intermediate oxidized dexamethasone were dissolved in N, N-dimethyl Dimethyl formamide (DMF), the two solutions were mixe...

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Abstract

The invention relates to preparations of a cationic polymer modified by a steroid hormone and a gene composite thereof. The technical problems to be solved by the invention are to provide a cationic polymer with multiple actions such as Cell nucleus targeting function, auxiliary tumor therapy, auxiliary anti-inflammatory therapy and the like, and a preparation method of the cationic polymer, and the method has simple process, reliable application and low cost. The preparation method of the polymer comprises the steps of dissolving the steroid hormone in an organic solvent, oxidizing with an oxidant, purifying and drying to obtain the oxidized steroid hormone; and dissolving the cationic polymer and the oxidized steroid hormone in the organic solvent, adding a catalytic dehydrating agent for reaction, purifying and drying to obtain the cationic polymer modified by the steroid hormone. The invention also provides an application of the cationic polymer as a gene carrier. The invention has the advantages that the composite formed by the polymer and the plasmid DNA has good targeting, excellent safety, high transfection efficiency and wide gene adaptability.

Description

technical field [0001] The invention relates to the field of cationic polymer gene carrier and gene therapy, in particular to a preparation method and application of a steroid hormone-modified cationic polymer. The present invention also relates to the formation of complexes between polymers and plasmid DNA and their use. Background technique [0002] Gene therapy is a kind of molecular therapy technology that traces back to the source of the disease by delivering the target gene as a "drug" into the patient's body to treat the disease. Gene therapy is an effective treatment for many congenital and acquired diseases (such as cancer, autoimmune diseases, diabetes, heart disease, hypertension, etc.), which can produce biologically active factors in the body or prevent abnormalities in cells Mechanisms to prevent, alleviate, compensate or correct corresponding diseases, and finally cure various diseases. Therefore, gene therapy will be the preferred strategy to solve diseases...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00C08G73/04A61K47/60A61K47/61
Inventor 周建平姚静范颖卢韵
Owner CHINA PHARM UNIV