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A preparation method of doxorubicin controlled-release chitosan nanoparticles with ph/redox double response

The technology of chitosan nanoparticles and doxorubicin is applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, pharmaceutical formulas, etc., and can solve the problems of drug structure damage, escape and inactivation, etc. To achieve the effect of convenient operation, improve transportation efficiency, and simple preparation technology

Active Publication Date: 2018-12-04
OCEAN UNIV OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, if the drug is retained in the endosome / lysosome, the acidic environment and the presence of enzymes will cause the structure of the drug to be damaged and inactivated, and the drug needs to escape from the endosome / lysosome in time

Method used

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  • A preparation method of doxorubicin controlled-release chitosan nanoparticles with ph/redox double response
  • A preparation method of doxorubicin controlled-release chitosan nanoparticles with ph/redox double response
  • A preparation method of doxorubicin controlled-release chitosan nanoparticles with ph/redox double response

Examples

Experimental program
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Effect test

Embodiment 1

[0017] Weigh 2 mg of mercapto-chitosan, dissolve it in 2 mL of 1 mM hydrochloric acid solution, add dropwise 0.3 mL of 1 mg / ml doxorubicin hydrochloride solution under stirring conditions, and obtain mixed solution 1, take 3 mg of 150 kDa molecular weight Carboxymethyl chitosan was dissolved in 3 mL of deionized water, and 0.1 mL of sodium tripolyphosphate solution with a concentration of 2% (w / v) was added dropwise under stirring conditions to obtain mixed solution 2, and mixed solution 1 was added dropwise to In the mixed solution 2, the dropping rate was 30 drops / min, the pH was adjusted to pH 7.5 with hydrochloric acid, the reaction was stirred at room temperature for 1 h, and the ultrasonic power was 200 W for 5 min, 2 s on, 1 s off, in Add 0.05 mL of 30% hydrogen peroxide dropwise under stirring conditions, stir at room temperature for 2 h, centrifuge at 15,000 rpm for 30 min, remove the supernatant, and freeze-dry to obtain a controlled-release doxorubicin with pH / redox ...

Embodiment 2

[0019] Weigh 2 mg of mercaptochitosan, dissolve it in 2 mL of 1 mM hydrochloric acid solution, add dropwise 0.3 mL of 1 mg / ml doxorubicin hydrochloride solution under stirring conditions, and obtain mixed solution 1, take 4 mg of 400 kDa molecular weight Carboxymethyl chitosan was dissolved in 4 mL of deionized water, and 0.2 mL of sodium tripolyphosphate solution with a concentration of 2% (w / v) was added dropwise under stirring conditions to obtain mixed solution 2, and mixed solution 1 was added dropwise to In the mixed solution 2, the dropping rate was 30 drops / min, the pH was adjusted to pH 8.0 with hydrochloric acid, the reaction was stirred at room temperature for 1 h, and ultrasonically mixed, the ultrasonic power was 200 W, the time was 5 min, 2 s on, 1 s off, and Add 0.05 mL of 30% hydrogen peroxide dropwise under stirring conditions, stir at room temperature for 2 h, centrifuge at 15,000 rpm for 30 min, remove the supernatant, and freeze-dry to obtain a controlled-re...

Embodiment 3

[0021] Weigh 2 mg of mercapto-chitosan, dissolve it in 2 mL of 1 mM hydrochloric acid solution, add dropwise 0.3 mL of 1 mg / ml doxorubicin hydrochloride solution under stirring conditions, and obtain mixed solution 1, take 3 mg of 1500 kDa molecular weight Carboxymethyl chitosan was dissolved in 3 mL of deionized water, and 0.5 mL of sodium tripolyphosphate solution with a concentration of 2% (w / v) was added dropwise under stirring conditions to obtain mixed solution 2, and mixed solution 1 was added dropwise to In the mixed solution 2, the dropping rate was 30 drops / min, the pH was adjusted to pH 6.0 with hydrochloric acid, the reaction was stirred at room temperature for 1 h, and the ultrasonic power was 200 W for 5 min, 2 s on, 1 s off, in Add 0.05 mL of 30% hydrogen peroxide dropwise under stirring conditions, stir at room temperature for 2 h, centrifuge at 15,000 rpm for 30 min, remove the supernatant, and freeze-dry to obtain a controlled-release doxorubicin with pH / redox...

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Abstract

The invention relates to a preparation method of amycin controlled-release chitosan nano particles with pH / oxido-reduction dual response. Thiolated chitosan, carboxymethyl chitosan, sodium tripolyphosphate, doxorubicin hydrochloride and hydrogen peroxide are taken as raw materials. The preparation method comprises the following steps: mixing a thiolated chitosans solution with a doxorubicin hydrochloride solution so as to obtain a solution I; mixing a carboxymethyl chitosan solution with a sodium tripolyphosphate solution so as to obtain a mixed solution II; dropwise adding the mixed solution I into the mixed solution II while stirring, controlling the dosage of carboxymethyl chitosan and thiolated chitosan, regulating the ph value of the solution to 6-8, performing ultrasonic blending, performing ion crosslinking and polymer condensing, then dropwise adding hydrogen peroxide into the system so as to finish oxidization crosslinking, performing room-temperature stirring reaction, separating products, and drying the products to obtain the amycin controlled-release chitosan nano particles with pH / oxido-reduction dual response. The amycin controlled-release chitosan nano particles with pH / oxido-reduction dual response is capable of escaping away from tumor cell endosome / lysosome, is capable of automatically regulating and controlling to realize cytoplast release based on unique microenvironments of tumor cells, improving the amycin medicine delivery efficiency and the medical effect, and has a favorable research and development application background in multiple aspects such as medicine and medical materials.

Description

technical field [0001] The invention relates to a preparation method of doxorubicin controlled-release chitosan nanoparticles with pH / redox double response. Background technique [0002] Nano-drugs can achieve targeted delivery and slow release of chemotherapy drugs and thus become a research hotspot. Targeted delivery of drugs in vivo is a characteristic of spontaneously responding to the in vivo environment and tumor microenvironment to regulate drug release, and drug carriers need to have corresponding functional properties. Tumor cells have unique environmental characteristics (such as pH, reducing properties, temperature, enzymes, etc.), and environment-sensitive carriers respond to single or multiple environmental characteristics to spontaneously control drug release in the correct time and space. On the one hand, the internal environment of endosomes / lysosomes is weakly acidic (pH 4.5-6.5), and pH-sensitive carriers based on groups such as orthoesters, hydrazones, or...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61K47/36A61K47/02A61K31/704A61P35/00
CPCA61K9/0002A61K9/5115A61K9/5161A61K31/704
Inventor 孔明左亚军冯超陈西广程晓杰刘雅
Owner OCEAN UNIV OF CHINA
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