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A kind of doxorubicin and gene drug co-delivery nano drug loading system and preparation method

A gene drug and nano-drug-loading technology, applied in drug combination, gene therapy, pharmaceutical formulation, etc., can solve the problem of inability to completely and effectively reverse tumor MDR, achieve sensitization toxicity, high encapsulation rate, and improve chemotherapy efficacy. Effect

Active Publication Date: 2021-03-02
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the current chemotherapeutic drugs and gene drug co-delivery cationic liposomes only use gene drugs to inhibit the expression of a certain MDR-related protein in tumor cells, and cannot completely and effectively reverse tumor MDR.

Method used

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  • A kind of doxorubicin and gene drug co-delivery nano drug loading system and preparation method
  • A kind of doxorubicin and gene drug co-delivery nano drug loading system and preparation method
  • A kind of doxorubicin and gene drug co-delivery nano drug loading system and preparation method

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preparation example Construction

[0032] The present invention also provides a preparation method of the above-mentioned doxorubicin and gene drug co-delivery nano-loading system, comprising the following steps:

[0033]Firstly, the membrane material is prepared into liposome colostrum by thin film hydration method. In the present invention, there is no special limitation on the specific operation steps of the thin film hydration method, and methods well known to those skilled in the art can be used. In the present invention, it is preferred that the liposomal colostrum step is specifically: the chloride salt of 1,2-dioleoyl-3-trimethylammonium-propane, dipalmitoylphosphatidylcholine, TPGS and Cholesterol is dissolved in chloroform according to the above-mentioned prescription ratio, and the chloroform is removed under reduced pressure to form a dry lipid film. Ammonium sulfate solution is added to the dry lipid film, and the liposome colostrum is formed by hydration in a water bath at 40-50°C.

[0034] In th...

Embodiment 1

[0051] Preparation of blank cationic liposomes (TPGS-LPs) with 1% TPGS content

[0052] Dissolve 4.22mg of DOTAP, 4.44mg of DPPC, 0.23mg of TPGS and 1.11mg of cholesterol in 4mL of chloroform and place in a 50mL round bottom flask, and remove the chloroform by rotary evaporation under a reduced pressure of 0.1MPa and a water bath at 40°C to form a dry lipid film; add 1mL of 123mM ammonium sulfate solution was hydrated in a water bath at 40°C for 1 hour to obtain liposome colostrum; liposome colostrum was passed through a 100nm polycarbonate membrane 19 times using a micro-liposome extruder to obtain 1% TPGS- LPs blank liposomes, the TPGS content is 1% based on the total lipid mole percentage.

Embodiment 2

[0054] Preparation of blank cationic liposomes (TPGS-LPs) with 2% TPGS content

[0055] Dissolve 4.15mg DOTAP, 4.36mg DPPC, 0.45mg TPGS and 1.04mg cholesterol in 4mL chloroform and place in a 50mL round-bottom flask, and remove the chloroform by rotary evaporation under 0.1MPa decompression and 40°C water bath to form a lipid dry film; add 1mL of 123mM ammonium sulfate solution was hydrated in a water bath at 40°C for 1 hour to obtain liposome colostrum; liposome colostrum was passed through a 100nm polycarbonate membrane 19 times using a micro-liposome extruder to obtain 2% TPGS- LPs blank liposomes, the TPGS content is 2% based on the total lipid mole percentage.

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Abstract

The invention provides an adriamycin and gene medicine co-transporting nano medicine carrying system and a preparation method. The co-transporting nano medicine carrying system is TPGS modified cationic liposome for co-carrying adriamycin and gene medicine, wherein a membrane material of the cationic liposome is prepared from 1,2-dioleoyl-3-trimethylammonio-propane or chlorate of the 1,2-dioleoyl-3-trimethylammonio-propane, dipalmitoyl phosphatidylcholine, TPGS and cholesterol. The prepared co-transporting nano medicine carrying system disclosed by the invention has a higher adriamycin encapsulating efficiency, stability of the co-transporting nano liposome is improved; meanwhile, complete inhibition on a tumor cell efflux pump can be achieved by only adjusting a formula, the purposes of two drug resistance mechanisms of inhibiting tumor medicine efflux and resisting apopotosis are achieved at the same time, and tumor multidrug resistance can be more completely and more effectively reversed.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a nano drug-carrying system and a preparation method for co-transporting doxorubicin and gene drug to reverse tumor drug resistance. Background technique [0002] At present, chemotherapy is the main means of tumor treatment, but multidrug resistance (MDR) is prone to occur in patients during chemotherapy, which makes it difficult to obtain good curative effect of chemotherapy. Clinically, combined chemotherapy or chemotherapy drugs are used in combination with other intervention drugs to further improve the efficacy of chemotherapy and reduce the occurrence of tumor drug resistance. The co-delivery nano-drug delivery system can realize the co-loading of multiple drugs, has the advantages of stable drug release behavior, tumor targeting, and less toxic side effects, and has become a hot spot in the research of anticancer drugs in recent years. [0003] Doxorubicin liposome As...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K47/22A61K47/18A61K45/06A61K47/69A61K47/60A61K47/54A61K31/704A61K31/713A61K48/00A61P35/00
CPCA61K9/1271A61K9/1277A61K31/704A61K31/713A61K45/06A61K47/186A61K47/22A61K48/0025A61K2300/00
Inventor 刘卫谭熙方彦李颖寰刘旭涵饶荣任园园
Owner HUAZHONG UNIV OF SCI & TECH
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