Drug liposome/p53 gene compound and preparation method and application thereof

A technology of p53 gene and liposome, which is applied in the field of tumor treatment, can solve the problems that resveratrol is easy to be oxidized and decomposed, and its application is limited, and achieve the effect of large clinical application value, low cytotoxicity and high protein expression

Inactive Publication Date: 2017-05-24
DALIAN NATIONALITIES UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, resveratrol is easily oxidatively decomposed in the presence of light, heat and oxidants, which limits its application in the food and pharmaceutical industries to a certain extent.

Method used

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  • Drug liposome/p53 gene compound and preparation method and application thereof
  • Drug liposome/p53 gene compound and preparation method and application thereof
  • Drug liposome/p53 gene compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Dissolve the cationic lipid CDO14 and resveratrol in the organic solvent of methanol and chloroform, add the co-lipid DOPE to fully dissolve, the mass ratio of cationic lipid, resveratrol and co-lipid is 5:1:1, Then vortex and shake for 10 seconds to mix evenly, blow the film with inert gas for 10 minutes, vacuum dry at 25°C for 12 hours, then add water and sonicate at 25°C to prepare an aqueous solution with a concentration of 0.5mg / mL, and separate it by a Sephadex column after centrifugation. Obtain drug liposome, then mix drug liposome and p53 gene, the mass ratio of drug liposome and p53 gene is 1:1, vortex and oscillate for 10 seconds to mix evenly, incubate at 20°C for 10 min, and prepare by electrostatic compounding get.

Embodiment 2

[0035] Dissolve the cationic lipid CDO14 and resveratrol in the organic solvent of methanol, add co-lipid cholesterol to fully dissolve, the mass ratio of cationic lipid, resveratrol and co-lipid is 10:1:1, and then vortex Shake for 15 seconds to mix evenly, blow film with inert gas for 15 minutes, vacuum dry at 30°C for 18 hours, then add water and ultrasonicate at 30°C to prepare an aqueous solution with a concentration of 1.0mg / mL, centrifuge and separate through a Sephadex column to obtain the drug Liposome, and then mix the drug liposome and p53 gene, the mass ratio of drug liposome and p53 gene is 2:1, mix evenly by vortexing for 15 seconds, incubate at 25°C for 15 minutes, and obtain by electrostatic compounding method.

Embodiment 3

[0037]Dissolve cationic lipid CDO12 and resveratrol in the organic solvent of ethyl acetate, add colipid DOPE to fully dissolve, the mass ratio of cationic lipid, resveratrol and colipid is 20:1:1, Then vortex and shake for 20 seconds to mix evenly, blow the film with inert gas for 20 minutes, vacuum dry at 40°C for 24 hours, add water and sonicate at 35°C to prepare an aqueous solution with a concentration of 1.5mg / mL, and separate it by a Sephadex column after centrifugation. Obtain drug liposome, then mix drug liposome and p53 gene, the mass ratio of drug liposome and p53 gene is 3:1, vortex and oscillate for 20 seconds to mix evenly, incubate at 30°C for 20 min, and prepare by electrostatic compounding get.

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Abstract

The invention provides a drug liposome / p53 gene compound and a preparation method and application thereof. The compound is composed of a drug liposome containing resveratrol and a p53 gene. The invention further provides the preparation method of the drug liposome / p53 gene compound. The preparation method comprises the following steps: taking polypeptide type positive ion lipoid, auxiliary lipoid and the resveratrol as main raw materials, orderly adopting a film dispersion method, an ultrasonic hydration method and a gel chromatographic column separation method to prepare a drug liposome, and then mixing the drug liposome with the p53 gene to prepare the drug liposome / p53 gene compound through an electrostatic compounding method. The drug liposome / p53 gene compound provided by the invention activates the p38MAPK kinase activity through the resveratrol so as to induce the activation of the p53 gene, the p53 gene is enabled to express a wild type p53 protein, the antitumor effects of the resveratrol and the p53 gene are synergistically played to trigger the apoptosis of tumor cells, thereby achieving an aim of treating the tumor. The in vitro biological study shows that the compound has a certain cell proliferation inhibition ability, has high wild type p53 protein expression, provides a new thought for the tumor treatment and has a potential application value.

Description

[0001] Technical field: [0002] The present invention relates to a drug liposome / p53 gene complex, more specifically to the preparation of a polypeptide-type cationic drug liposome containing resveratrol and its formation of a novel anti-tumor complex preparation with p53 gene The invention belongs to a novel pharmaceutical preparation in the field of tumor treatment and a preparation method and application thereof. [0003] Background technique: [0004] The combined delivery of drugs and genes is a biomedical treatment method that uses carriers to efficiently deliver anticancer drugs and genes into tumor cells, and release drugs and genes in a timely manner to achieve the goal of synergistic treatment. At present, the combined transport therapy system mainly includes drug / drug, drug / siRNA, drug / pDNA and other therapeutic method systems for various diseases. Carrier liposomes carrying drugs and nucleic acids also include polymeric carriers such as polymer micelles and PLGA n...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K31/05A61K9/127A61P35/00
CPCA61K9/1277A61K31/05A61K48/0058A61K2300/00
Inventor 张树彪许晓东李一楠陈会英赵轶男
Owner DALIAN NATIONALITIES UNIVERSITY
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