Drug loading system loaded with anti-cancer drug as well as preparation method and application of drug loading system

An anti-cancer drug and drug-carrying technology, which is applied in the direction of pharmaceutical formulations, anti-tumor drugs, drug combinations, etc., can solve problems such as narrow therapeutic index, organ intolerance to drugs, etc., to increase biodistribution, improve bioavailability, The effect of rapid mass production

Pending Publication Date: 2022-08-02
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Single drug has a narrow therapeutic index and requires multiple dosing, often resulting in organ intolerance to the drug, hence the focus on the development of nanocarrier formulations

Method used

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  • Drug loading system loaded with anti-cancer drug as well as preparation method and application of drug loading system
  • Drug loading system loaded with anti-cancer drug as well as preparation method and application of drug loading system
  • Drug loading system loaded with anti-cancer drug as well as preparation method and application of drug loading system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0032] Preparation of empty neutral liposomes:

[0033] 2.57 mg (69 equiv.) 1,2-dioleoylglycerol-3-phosphoethanolamine (DOPE), 0.77 mg (40 equiv.) cholesterol (CHOL), 0.5 mg (4 equiv.) 1,2-dimyristoyl- sn-glycerol-3-methoxypolyethylene glycol (DMG-PEG) was dissolved in dichloromethane; 0 mg (0 equiv) of 1,2-dioleoyl-sn-glycerol-3-dissolved in dichloromethane was added Phosphate ester (DOPA, the two were mixed evenly, and the organic reagent was removed by rotary evaporation for 5 min to obtain a layer of phospholipid film; the obtained phospholipid film was hydrated with 4 ml of distilled water, ultrasonicated for 5 min, and the solution was transferred to a dialysis bag (MW=14000) , dialysis with pure water for 12h under stirring conditions, to obtain empty neutral liposome solution (0% Liposomes).

[0034] The particle size of the unloaded liposome solution is obtained by testing, and the results are as follows figure 1 As shown, the particle size of the liposome is betwee...

Embodiment 1-2

[0037] Preparation of empty 10% anionic liposomes and cationic liposomes:

[0038] (1) 2.22 mg (69 equiv.) 1,2-dioleoylglycerol-3-phosphoethanolamine (DOPE), 0.67 mg (40 equiv.) cholesterol (CHOL), 0.43 mg (4 equiv.) 1,2-dimeat Myristoyl-sn-glycero-3-methoxypolyethylene glycol (DMG-PEG) was dissolved in dichloromethane; 0.52 mg (12.6 equiv.) of 1,2-dioleoyl-sn-dissolved in dichloromethane was added Glycerol-3-phosphate (DOPA), the remaining steps were the same as those of Example 1-1 (except for transmission observation) to obtain an unloaded anionic liposome solution (10% DOPALiposomes).

[0039] (2) 2.32 mg (69 equiv.) 1,2-dioleoylglycerol-3-phosphoethanolamine (DOPE), 0.7 mg (40 equiv.) cholesterol (CHOL), 0.451 mg (4 equiv.) 1,2-dimeat Myristoyl-sn-glycero-3-methoxypolyethylene glycol (DMG-PEG) was dissolved in dichloromethane; 0.369 mg (12.6 equiv.) of 1,2-dioleoyl-3-dissolved in dichloromethane was added (Dimethylamino)propane (DODAP), the remaining steps were the same...

Embodiment 1-3

[0042] Preparation of empty 30% anionic liposomes and cationic liposomes:

[0043] (1) 2.22 mg (69 equiv.) 1,2-dioleoylglycerol-3-phosphoethanolamine (DOPE), 0.67 mg (40 equiv.) cholesterol (CHOL), 0.43 mg (4 equiv.) 1,2-dimeat Myristoyl-sn-glycero-3-methoxypolyethylene glycol (DMG-PEG) was dissolved in dichloromethane; 0.52 mg (12.6 equiv.) of 1,2-dioleoyl-sn-dissolved in dichloromethane was added Glycerol-3-phosphate (DOPA), the remaining steps were the same as those of Example 1-1 (except for transmission observation) to obtain an unloaded anionic liposome solution (10% DOPALiposomes).

[0044] (2) 2.32 mg (69 equiv.) 1,2-dioleoylglycerol-3-phosphoethanolamine (DOPE), 0.7 mg (40 equiv.) cholesterol (CHOL), 0.451 mg (4 equiv.) 1,2-dimeat Myristoyl-sn-glycero-3-methoxypolyethylene glycol (DMG-PEG) was dissolved in dichloromethane; 0.369 mg (12.6 equiv.) of 1,2-dioleoyl-3-dissolved in dichloromethane was added (Dimethylamino)propane (DODAP), the remaining steps were the same...

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Abstract

The invention belongs to the technical field of nano medicaments, and discloses a drug loading system loaded with an anti-cancer drug as well as a preparation method and application of the drug loading system. The preparation method comprises the following steps: dissolving 1, 2-dioleoylglycerol-3-phosphoethanolamine, cholesterol, 1, 2-dimyristoyl-sn-glycerol-3-methoxyl polyethylene glycol, 1, 2-dioleoyl-sn-glycerol-3-phosphate or 1, 2-dioleoyl-3-(dimethylamino) propane and an anti-cancer drug in dichloromethane together, adding a proper amount of ethanol, stirring, adding a proper amount of ethanol, stirring, adding a proper amount of ethanol, stirring, adding a proper amount of ethanol, stirring, adding a proper amount of ethanol, stirring, adding a proper amount of ethanol, stirring, adding a proper amount of water, and stirring. And hydrating a layer of phospholipid film obtained by rotary evaporation with triple distilled water, and dialyzing after ultrasonic treatment to obtain a liposome solution loaded with the anti-cancer drug. The drug loading system is provided with a lipophilic shell composed of a phospholipid bilayer, and a water core is arranged in the lipophilic shell and can wrap a hydrophobic or hydrophilic drug; the potential is changed along with the change of the mole percentage of the fourth phospholipid; the blood circulation time of the medicine in the body can be prolonged, and the bioavailability of the medicine is improved; the medicine is mainly distributed in liver and spleen in vivo.

Description

technical field [0001] The invention relates to the technical field of nano-medicine, in particular to a drug-carrying system for loading anti-cancer drugs and a preparation method and application thereof. Background technique [0002] According to statistics, in recent years, the incidence of neurodegenerative diseases, cancer, cardiovascular diseases and other related diseases has increased significantly, and cancer has become the second leading cause of death in the world, which poses a huge threat to human life. So far, there are many treatment methods for cancer. Conventional clinical treatment includes surgical resection, drug therapy, radiation therapy, etc., and the use of chemical drugs to intervene or treat tumor diseases is one of the more commonly used methods. A single drug has a narrow therapeutic index, requires multiple administrations, and often leads to organ intolerance, so people focus on the development of nanocarrier formulations. Nanocarriers are nano...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K31/337A61K31/704A61K47/14A61K47/24A61K47/28A61P35/00
CPCA61K9/1277A61K47/24A61K47/28A61K47/14A61K31/704A61K31/337A61P35/00
Inventor 陈忠平黄旭孙佳佳刘雪蒙翁凌燕朱俐
Owner NANTONG UNIVERSITY
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