Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Core-shell structure nanoparticles for reduction/enzyme/pH multi-responsive drug release

A core-shell structure and nanoparticle technology, applied in antitumor drugs, drug combinations, pharmaceutical formulations, etc., can solve problems such as non-degradability and high cytotoxicity, and achieve easy drug release, high drug loading, and improved blood stability. Effect

Inactive Publication Date: 2016-05-04
JINAN UNIVERSITY
View PDF9 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Tumor tissue has very different environmental characteristics from normal tissue, such as endosomes / lysosomes are acidic (pH ~ 5.0) and rich in glutathione (GSH), which can be used to design pH responsiveness and disulfide bonds Reduction-responsive drug-loaded nanoparticles, such as the recently reported PEG-PAsp(MEA)-PEI drug-loaded nanoparticles for the study of lung cancer A549 cells and the PEG-oDS / LDS drug-loaded nanoparticles for the study of uterine cancer Hela cells, However, there are still great challenges in how to assist drugs to escape from endosomes / lysosomes to the cytoplasm quickly, although the proton sponge effect of PEI (polyethyleneimine) can help drugs escape from endosomes / lysosomes. Escape from the enzyme body, but it is controversial because PEI is non-degradable and highly toxic to cells

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Core-shell structure nanoparticles for reduction/enzyme/pH multi-responsive drug release
  • Core-shell structure nanoparticles for reduction/enzyme/pH multi-responsive drug release
  • Core-shell structure nanoparticles for reduction/enzyme/pH multi-responsive drug release

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] (1) Preparation of core layer chitosan-based highly drug-loaded nanomicelles

[0078] ① Dissolve 150mg of SNX2112 and 40mg of succinic anhydride in 10mL of DMSO; add 0.1mL of triethylamine to the above solution, and conduct an esterification reaction at room temperature for 72 hours; rotate the solution after the reaction to remove the solvent and triethylamine under reduced pressure, and then Washing with acetone to remove the residual unreacted drug, then washing with water to remove the residual unreacted succinic anhydride, and freeze-drying to obtain the succinic anhydride modified drug;

[0079] ② Dissolve 20 mg of the succinic anhydride modified drug prepared in step ① in 20 mL of DMSO, and add 0.07 mmol of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to the solution (EDC·HCl) and 0.07mmol N-hydroxysuccinimide (NHS), activation reaction 0.5h; take 40mgCs dissolved in 6mL2% (W / W) acetic acid solution, then add to 34mL MES buffer solution of pH=5.6 a...

Embodiment 2

[0088] (1) Preparation of core layer chitosan-based highly drug-loaded nanomicelles

[0089] ①Dissolve 50mg of paclitaxel and 20mg of succinic anhydride in 10mL of DMSO; add 0.5mL of triethylamine to the above solution, and perform esterification reaction at room temperature for 24 hours; spin evaporate the solution under reduced pressure to remove the solvent and triethylamine Amine, then wash with acetone to remove residual unreacted drug, then wash with water to remove residual unreacted succinic anhydride, obtain succinic anhydride modified drug after freeze-drying;

[0090] ② Dissolve 20 mg of the succinic anhydride modified drug prepared in step ① in 20 mL of DMSO, and add 0.7 mmol of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to the solution (EDC·HCl) and 0.07mmol N-hydroxysuccinimide (NHS), activation reaction for 24h; take 100mg of Cs dissolved in 3mL of 2% (W / W) acetic acid solution, and then add to 17mL of MES buffer solution mixed solvent with pH=5...

Embodiment 3

[0099] (1) Preparation of core layer chitosan-based highly drug-loaded nanomicelles

[0100]①Dissolve 100mg of doxorubicin and 30mg of succinic anhydride in 10mL of DMSO; add 0.25mL of triethylamine to the above solution, and perform esterification reaction at room temperature for 48 hours; spin evaporate the solution after the reaction to remove the solvent and triethylamine Amine, then wash with acetone to remove residual unreacted drug, then wash with water to remove residual unreacted succinic anhydride, obtain succinic anhydride modified drug after freeze-drying;

[0101] ② Dissolve 50 mg of the succinic anhydride modified drug prepared in step ① in 20 mL of DMSO, and add 0.35 mmol of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to the solution (EDC·HCl) and 0.07mmol N-hydroxysuccinimide (NHS), activation reaction for 12h; take 50mg of Cs dissolved in 3mL of 2% (W / W) acetic acid solution, then add to 17mL of MES buffer solution with pH=5.6 and sonicate Aft...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
The average particle sizeaaaaaaaaaa
Average particle sizeaaaaaaaaaa
The average particle sizeaaaaaaaaaa
Login to View More

Abstract

The invention belongs to the field of biomedical materials and drug control release and particularly relates to core-shell structure nanoparticles for reduction / enzyme / pH multi-responsive drug release. Firstly, chitosan-based nano micelle with high drug loading is prepared with a chemical method and a physical method and taken as a core layer, hyaluronic acid molecules modified by histidine and cysteamine are taken as a shell layer, the core layer and the shell layer form a core-shell structure through electrostatic interaction, and the core-shell structure nanoparticles for reduction / enzyme / pH multi-responsive drug release are obtained. The prepared drug-loaded nanoparticles have the characteristics of active targeting at cancer cells, high drug loading, good stability in blood, rapid drug release through multiple stimulating response of reduction / hyaluronidase / pH and the like, can effectively kill the cancer cells and have great significance in cancer treatment.

Description

technical field [0001] The invention belongs to the field of biomedical materials and drug controlled release, in particular to a core-shell nanoparticle with reduction / enzyme / pH multiple responsive drug release. Background technique [0002] According to the statistics of the Ministry of Health in 2006, cancer has surpassed cardiovascular disease and ranked first in the cause of death. In my country, more than 1.6 million people die from cancer every year, and the treatment cost is as high as 150 billion yuan. The annual cancer mortality rate is on the rise. Among them, the incidence of breast cancer ranks first among female malignant tumors. Cancer treatment has thus become the current international standard. the most researched areas in the world. Drug therapy is currently the main treatment for cancer, but the biggest problem is that anticancer drugs cannot stay locally in the tumor tissue but are distributed in various tissues and organs of the body, resulting in seriou...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K9/51A61K31/337A61K31/704A61K31/416A61K47/36A61K47/18A61K47/48A61P35/00
CPCA61K9/5161A61K31/337A61K31/416A61K31/704
Inventor 赵剑豪王祥林容建华
Owner JINAN UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com