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Preparation method and application of drug controlled release nano-system sensitive to tumor microenvironment

A tumor microenvironment and drug controlled release technology, applied in the field of drug controlled release, to achieve the effect of improving the ability to enter cells, promoting adhesion, and high yield

Inactive Publication Date: 2016-08-31
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The technical problem to be solved by the present invention is to design a high-efficiency polysaccharide-based tumor microenvironment multi-sensitive drug controlled release nano system and apply it to cancer treatment. The preparation method of the drug controlled release nano system is green, simple and efficient. The drug controlled-release nanosystem prepared by this method has both reduction sensitivity and weak acid sensitivity, avoiding the shortcomings of a single sensitive drug controlled-release nanosystem, and has good biocompatibility and cancer treatment effect

Method used

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  • Preparation method and application of drug controlled release nano-system sensitive to tumor microenvironment

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Embodiment 1

[0026] Step A: Preparation of reduction-sensitive nanoparticles based on dextran-methacrylic acid system: Dissolve 1.00 g of dextran (molecular weight of 40,000 Da) in 100 mL of water, stir until fully dissolved, pass nitrogen to deoxidize for 1 hour, and A dilute nitric acid solution containing 0.47 g of ammonium cerium nitrate was added under nitrogen protection and uniform stirring, so that the final pH of the reaction system was between 1-2. After about 5 minutes, 0.50 mL of methacrylic acid monomer was added, and half an hour later, 0.096 g of diallyl disulfide crosslinking agent (dissolved in 1 mL of dimethyl sulfoxide solution) was added, and the reaction was carried out at 30° C. for 4 hours. After the reaction, dialyze in pure water for one week to ensure the removal of impurities such as unreacted monomers in the reaction system, that is, to obtain a reducing environment-sensitive nanoparticle aqueous solution based on the dextran-acrylic acid system, and obtain nanop...

Embodiment 2

[0031]Step A: Preparation of reduction-sensitive nanoparticles based on the dextran-hydroxyethyl acrylate system: Dissolve 1.00 g of dextran (molecular weight: 40,000 Da) in 100 mL of water, stir until fully dissolved, and deoxidize with nitrogen for 1 hour, Under nitrogen protection and uniform stirring, dilute nitric acid solution containing 0.47 g of ceric ammonium nitrate was added to make the final pH of the reaction system between 1-2. After about 5 minutes, 0.62 mL of hydroxyethyl acrylate monomer was added, and half an hour later, 0.096 g of diallyl disulfide crosslinking agent (dissolved in 1 mL of dimethyl sulfoxide solution) was added, and the reaction was carried out at 30°C for 4 hours. After the reaction, dialyze in pure water for one week to ensure the removal of impurities such as unreacted monomers in the reaction system, that is, to obtain a reducing environment-sensitive nanoparticle aqueous solution based on the dextran-methyl acrylate system, which is obtai...

Embodiment 3

[0036] Step A: Preparation of temperature-sensitive reduction-sensitive nanoparticles based on hydroxypropyl cellulose-glycidyl methacrylate system: 0.6 g of temperature-sensitive hydroxypropyl cellulose (molecular weight 80,000 Da) Dissolve in 50mL water, stir until fully dissolved, pass argon for 1 hour to remove oxygen in the system, add 0.08g dilute nitric acid solution of ammonium cerium nitrate under argon protection and uniform stirring, so that the final pH of the reaction system is at 1- between 2. After about 10 minutes, 0.32 mL of glycidyl methacrylate was added, and after 30 minutes, 0.080 g of bisacrylcystamine cross-linking agent (dissolved in an appropriate amount of aqueous solution) was added and reacted at 30° C. for 4 hours. After the reaction is over, transfer to a dialysis bag and dialyze in pure water for three days to ensure removal of impurities such as unreacted monomers in the reaction system, that is, to obtain a hydroxypropyl cellulose-glycidyl meth...

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Abstract

The invention provides a preparation method of a drug controlled release nano-system sensitive to tumor microenvironment, the drug controlled release nano-system sensitive to tumor microenvironment prepared by the preparation method and an application of the drug controlled release nano-system for treating cancer. The drug controlled release nano-system is sensitive to both reduction and weak acid, and has good biocompatibility and cancer treatment effect.

Description

technical field [0001] The invention belongs to the field of drug controlled release, in particular to a preparation method of a drug controlled release nano system sensitive to tumor microenvironment and its application in cancer treatment. Background technique [0002] Tumor has always been one of the difficult problems that medical workers and researchers are trying to overcome. Chemotherapy is the most commonly used method to treat cancer in clinical medicine at present, but the selectivity of anticancer drugs to tumor sites is poor, which will cause great damage to normal tissues and produce strong side effects. Therefore, in recent years, researchers have proposed a drug delivery system, which is to load anti-tumor drugs into nanoparticles to form a drug delivery system. Because the system has a nanometer size, people can use the passive targeting (EPR) effect to deliver anti-tumor drugs Delivery to the tumor site, so as to realize the release of the drug in the tumor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K9/19A61K31/475A61K31/704A61K38/14A61P35/00C08F251/00C08F220/06C08F220/28C08F251/02C08F220/32
CPCA61K38/14A61K9/0002A61K9/19A61K31/475A61K31/704C08F251/00C08F251/02C08F220/286C08F220/325C08F220/281
Inventor 窦红静王灏尤佳毅李松营刘彦男
Owner SHANGHAI JIAO TONG UNIV
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