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Cationic liposome nucleic acid medicinal preparation as well as preparation method and application thereof

A technology of cationic liposomes and cationic lipids, which can be used in liposome delivery, other methods of inserting foreign genetic materials, drug combinations, etc. lower problem

Inactive Publication Date: 2015-02-18
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still difficulties in the clinical application of cationic liposomes
Due to the positive charge on the surface of the cationic liposome gene complex, it is easy to generate non-specific adsorption with serum proteins in plasma to form large-sized aggregates, which are easily cleared by the reticuloendothelial system, resulting in short blood circulation time , poor stability, low operating efficiency

Method used

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  • Cationic liposome nucleic acid medicinal preparation as well as preparation method and application thereof
  • Cationic liposome nucleic acid medicinal preparation as well as preparation method and application thereof
  • Cationic liposome nucleic acid medicinal preparation as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Synthesis of Lipid Molecule CL1 (Compound (I))

[0067] Weigh 50.27g (176.7mmol) of stearic acid, 18.3g (96.2mmol) of p-toluenesulfonic acid, dissolve about 350mL of toluene, and reflux reaction at a temperature of 110°C; after 1h, add 9.56g of (80.2mmol) N-methyldiethanolamine (NMA), react overnight; the next day, stop heating, add 30mL NaCl saturated solution for extraction. Use a rotary evaporator to remove the solvent toluene, add an appropriate amount of dichloromethane, and filter with suction to obtain a white solid, which is then purified by column chromatography to obtain the final product. Its structural characterization is as follows: figure 1 shown. The preparation of embodiment 2 cationic liposome nucleic acid drug preparation

Embodiment 2

[0067] Weigh 50.27g (176.7mmol) of stearic acid, 18.3g (96.2mmol) of p-toluenesulfonic acid, dissolve about 350mL of toluene, and reflux reaction at a temperature of 110°C; after 1h, add 9.56g of (80.2mmol) N-methyldiethanolamine (NMA), react overnight; the next day, stop heating, add 30mL NaCl saturated solution for extraction. Use a rotary evaporator to remove the solvent toluene, add an appropriate amount of dichloromethane, and filter with suction to obtain a white solid, which is then purified by column chromatography to obtain the final product. Its structural characterization is as follows: figure 1 shown. The preparation of embodiment 2 cationic liposome nucleic acid drug preparation

[0068] 1) Preparation of cationic liposomes: Weigh cationic lipid CL1, cholesterol and DSPE-PEG with a molar ratio of 6:3:1, dissolve them fully in ethanol, shake well, and form an oil phase to a concentration of 1 mg / mL; Measure 3 times the volume of ethanol and acidic buffer solutio...

Embodiment 3

[0071] The preparation of embodiment 3 cationic liposome nucleic acid drug preparation

[0072] 1) Preparation of cationic liposomes: Weigh cationic lipid CL1, cholesterol and DSPE-PEG with a molar ratio of 6:3:1, fully dissolve them in ether, shake well, and form an oil phase to a concentration of 1 mg / mL; Measure 3 times the volume of acidic buffer solution of diethyl ether with a pH value of 3.5 in a round bottom flask, and slowly inject the oil phase into the acidic buffer solution with a syringe in a water bath at 40°C under magnetic stirring at a rate of 40r / min and continue to stir for 2 hours to obtain a liposome suspension; the obtained liposome suspension is packed into a dialysis bag, and the ether in the liposome suspension is permeated with an acidic buffer solution as a dialysate, Change the dialysate every once in a while; put the dialyzed liposome sample into a centrifuge tube and dilute to the final system.

[0073]2) Prepare the working solution of the nucl...

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Abstract

The invention discloses a nucleic acid transfected cationic liposome, a nucleic acid medicinal preparation comprising a cationic liposome as well as a preparation method and use thereof. The cationic liposome comprises a cationic liposome, an auxiliary liposome and a polyethylene glycol modified neutral liposome. The cationic liposome nucleic acid medicinal preparation comprises the cationic liposome and the nucleic acid medicinal preparation. The cationic liposome disclosed by the invention serves as a non-virus gene vector and is low in cytotoxicity, strong in blood stability and high in gene silencing efficiency. The highest gene silencing efficiency on a HepG-2 cell which constantly expresses luciferase is 90.8%. The cationic liposome has an excellent anti-non-specific protein adsorptive property and long recyclability, thus improving the stability and the running efficiency of the liposome and effectively improving the effect of the nucleic acid medicine. The cationic liposome nucleic acid medicinal preparation can be used in the field of medicine and the like.

Description

technical field [0001] The invention belongs to the field of drug delivery, in particular to a cationic liposome as a pharmaceutical carrier, in particular to a cationic liposome containing a cationic lipid molecule CL1, a nucleic acid pharmaceutical preparation comprising the cationic liposome and a preparation method thereof and apply. Background technique [0002] Gene transfection is to transfer or transport nucleic acids with biological functions (including DNA, antisense oligonucleotides and RNAi) into cells and maintain the biological functions of nucleic acids in cells. Individual nucleic acid molecules are easily degraded by ribozymes in tissues or cells, and nucleic acid molecules themselves are negatively charged, which is not conducive to penetration into negatively charged cell membranes. [0003] The transfection efficiency of the early transfection method was very low, and it was ineffective for many cell lines, so it could not meet the needs of many scientif...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/48A61K48/00A61K47/04C12N15/87A61P7/04A61P3/06A61P35/00A61P9/00A61P31/18A61P29/00
Inventor 张欣董雅琼阳俊
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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