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Method for preparing glucocorticoid grafted gene drug delivery vector

A technology of glucocorticoids and drug delivery carriers, which is applied in gene therapy, pharmaceutical formulations, liposome delivery, etc., can solve the problems of low biocompatibility, achieve simple preparation process, improve gene transfection efficiency, and reduce toxicity Effect

Inactive Publication Date: 2011-09-28
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Linking glucocorticoids with small molecular weight PEI to obtain glucocorticoid-grafted polycations is a gene carrier material with high transfection efficiency and low cytotoxicity, but because polycations are not degradable in the body, they are biocompatible lower sex

Method used

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  • Method for preparing glucocorticoid grafted gene drug delivery vector
  • Method for preparing glucocorticoid grafted gene drug delivery vector
  • Method for preparing glucocorticoid grafted gene drug delivery vector

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Dissolve 10 mg of phospholipids and 0 to 4.83 mg of cholesterol in 15 mL of chloroform, and dissolve 3.2 to 67.45 mg of glucocorticoid-grafted polycations in distilled water (5 mL) that is 1 / 3 of the volume of chloroform, and prepare lipids by reverse evaporation. body. Specifically: add the water phase to the organic phase, vortex or sonicate for 10 to 30 minutes to form an emulsion, and remove chloroform under reduced pressure on a rotary evaporator to obtain a liposome suspension. The liposome solution is sonicated in a water bath for 5-20 minutes, squeezed through the membrane, and the pore size is 0.1-0.22 μm.

Embodiment 2

[0031] Take triamcinolone acetonide 217.25mg and dissolve it with anhydrous pyridine, and the solution is at 0°C, N 2 Under protection, under stirring, slowly add 78 μL of excess methanesulfonyl chloride dropwise, react at 0°C for 5 hours, add excess ice water (about 80 mL) at 0°C to the reaction solution to terminate the reaction, filter with suction, wash with ice water, and dry in vacuo. A white solid was obtained, which was the 21-position mesylate of triamcinolone acetonide.

[0032] Dissolve 133.9 mg of triamcinolone acetonide 21-position mesylate in excess of 4 times and Traut’s reagent 34.4 mg in 2 mL of anhydrous DMSO, and dissolve 112.5 mg of low molecular weight PEI 1800 in 2 mL of anhydrous DMSO. 2 Add dropwise to the former solution under protection and stir while adding. The reaction was carried out at room temperature for 4 hours, then 80 mL of excess iced ethyl acetate was added, and a pale yellow precipitate was obtained by filtration, which was dissolved by ...

Embodiment 3

[0033] Embodiment 3: NMR characterization of triamcinolone acetonide 21-position mesylate and triamcinolone acetonide-polyethyleneimine (TA-PEI)

[0034] An appropriate amount of triamcinolone acetonide 21-position mesylate was dissolved in deuterated DMSO, and 500MHz 1H-NMR scanning was performed. An appropriate amount of TA-PEI was dissolved in deuterium water, and a 500MHz 1H-NMR scan was performed. Please refer to the attached figure 2 . See the attached image 3 .

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Abstract

The invention provides a method for preparing a gene drug delivery vector of a glucocorticoid grafted polycation modified liposome, which is to utilize the hydrophobic property of glucocorticoid on a glucocorticoid grafted polycation to be combined with a liposome. The glucocorticoid grafted polycation modified liposome consists of the glucocorticoid grafted polycation, neutral phospholipid, cholesterol and distilled water, and is prepared by a reverse evaporation method. The method has the advantages that the combination of the glucocorticoid grafted polycation and the liposome can improve the transfection efficiency of the liposome, can also increase the biocompatibility of a polymer, reduce the toxicity, and can also improve the targeting delivery of the vector by performing target modification on the liposome. The method has reasonable design and simple preparation technology, and has good in vivo application prospect.

Description

technical field [0001] The invention relates to a preparation method of a drug delivery carrier, in particular to a preparation method of a gene delivery carrier of a polycation-modified liposome grafted with glucocorticoids. Background technique [0002] With the development of molecular biology, especially the establishment of human gene pools and the elucidation of human disease-related genes, gene therapy for diseases has emerged as the times require, and has developed into a new research field in contemporary medicine and biology. It is one of the most promising therapeutic options for the treatment of hereditary congenital diseases, malignant tumors, infectious diseases, etc. [0003] The current transfection vectors can basically be divided into two categories: viral vectors and non-viral vectors. Non-viral gene vectors can overcome many inherent problems of viral gene vectors, such as non-immunogenicity, non-genotoxicity, low cytotoxicity, low cost, etc. It is an ir...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K48/00A61K47/28A61K47/32
Inventor 金一马昆胡敏新齐岩王成润
Owner ZHEJIANG UNIV
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