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

Drug-loaded micelles with particle size reduction and surface charge reversal in response to acidic microenvironment and preparation method thereof

A technology of drug-loaded micelles and particle size, which can be used in pharmaceutical formulations, medical preparations with non-active ingredients, and medical preparations containing active ingredients, etc., can solve problems such as limited tumor penetration ability, and improve anti-tumor effects. , Improve the ability of penetration, the effect of long cycle time

Active Publication Date: 2021-08-27
SICHUAN UNIV
View PDF11 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art, and provide drug-loaded micelles that respond to the acidic microenvironment to achieve particle size reduction and surface charge reversal and its preparation method, so as to solve the problem that the existing nano-drug delivery system is difficult to achieve particle size reduction at the tumor site. The problem of limited tumor penetration ability due to the reduced diameter, endows the drug-loaded micelles with long-term circulation and the ability to penetrate tumors efficiently

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
  • Drug-loaded micelles with particle size reduction and surface charge reversal in response to acidic microenvironment and preparation method thereof
  • Drug-loaded micelles with particle size reduction and surface charge reversal in response to acidic microenvironment and preparation method thereof
  • Drug-loaded micelles with particle size reduction and surface charge reversal in response to acidic microenvironment and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] In this embodiment, the polymer prodrug is synthesized, and the synthetic route and steps are as follows:

[0053]

[0054] (1) Chain transfer agent 4-cyano-4-(thiobenzoyl)valeric acid (CPDB), 2-(hexamethyleneimine) ethanol methacrylate (HEME) monomer and initiator azo Diisobutyronitrile (AIBN) was dissolved in redistilled 1,4-dioxane (1,4-Dioxane), the molar ratio of HEME to CPDB was 80:1, and the molar ratio of AIBN to CPDB was 0.2: 1. The concentration of CPDB in 1,4-dioxane is 0.02mmol / mL. The resulting mixed solution was transferred to a pre-deoxygenated reaction bottle, followed by freezing-vacuum-nitrogen circulation three times to remove the oxygen in the reaction bottle, and then nitrogen protection and sealing the reaction bottle, and polymerized at 65 °C reaction, after 24 hours of polymerization reaction, the reaction was quenched with liquid nitrogen, dichloromethane was added to the obtained reaction liquid to dilute and precipitate in excess cold hexa...

Embodiment 2

[0075] In this example, the drug-loaded micelles were prepared on the basis of the polymer prodrug synthesized in Example 1, and the steps were as follows:

[0076] Take 3 mg of the polymer prodrug prepared in Example 1 and dissolve it in 200 μL of DMF to form a polymer prodrug solution, and slowly drop the polymer prodrug solution into 3 mL of pH=7.4 under ice bath and ultrasonic conditions with a power of 200 W. After the dropwise addition, continue to sonicate for 5 minutes in an ice bath, and then transfer to PBS with pH=7.4 to fully dialyze to remove DMF to obtain drug-loaded micelles.

[0077] Take 3 mg of the polymer prodrug prepared in Example 1 and dissolve it in 200 μL of DMF to form a polymer prodrug solution, and slowly drop the polymer prodrug solution into 3 mL of pH=6.7 under ice bath and ultrasonic conditions with a power of 200 W. After the dropwise addition, continue to sonicate for 5 minutes in an ice bath, and then transfer to PBS with pH=6.7 to fully dialy...

Embodiment 3

[0083] In this example, the particle size of the drug-loaded micelles prepared in Example 2 and Comparative Examples 3-4 was characterized by dynamic light scattering (DLS). Take the drug-loaded micelles prepared in Example 2 and Comparative Examples 3-4 under different pH conditions, and use PBS with corresponding pH values ​​to prepare drug-loaded micellar solutions with a concentration of 1 mg / mL and pH values ​​of 7.4 and 6.7, respectively. , the particle size of drug-loaded micelles was characterized by dynamic light scattering test. Measuring conditions: temperature 25°C, scattering angle 173°, each sample was measured three times. The results are shown in Table 2.

[0084] The drug-loaded micelles prepared in Example 2 and Comparative Example 3 were diluted with PBS of corresponding pH value to a drug-loaded micelle solution with a concentration of 100 μg / mL, and the drug-loaded micelles were characterized by transmission electron microscope (TEM) and atomic force micr...

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
particle diameteraaaaaaaaaa
particle diameteraaaaaaaaaa
particle diameteraaaaaaaaaa
Login to View More

Abstract

The present invention provides a polymer prodrug, based on the polymer prodrug, a drug-loaded micelle that responds to an acidic microenvironment to achieve particle size reduction and surface charge reversal is provided, and the drug-loaded micelle is composed of the polymer The prodrug is formed by self-assembly. Under the condition of human physiological pH value, the surface of the drug-loaded micelle is negatively charged. Drug-loaded micelles undergo charge reversal and particle size reduction. The present invention can solve the problem that the existing nano-drug delivery system is difficult to reduce the particle size at the tumor site and has limited penetration ability to tumors, and can break the limitation of nano-drugs to play an excellent anti-tumor effect, making the drug-loaded micelles It has excellent long-term circulation and the ability to gather to the tumor site, and at the same time improves the ability of the drug-loaded micelles to penetrate deep into the tumor, which can effectively improve the anti-tumor effect of the drug.

Description

technical field [0001] The invention belongs to the field of anti-tumor drug delivery systems, and relates to polymer prodrugs, drug-loaded micelles based on the polymer prodrugs that respond to acidic microenvironments to achieve particle size reduction and surface charge reversal, and their preparation methods. Background technique [0002] Cancer is one of the greatest threats to human life and health, and is the second leading cause of death in the world. Traditional chemotherapy drugs have the following disadvantages: poor water solubility and stability, low bioavailability and high toxicity and side effects, which limit their clinical application. Due to the unique advantages of prolonging the circulation time of drugs in the body, low toxicity and side effects, and realizing sustained and controlled release of drugs, nano-drug delivery systems have been extensively studied in recent years. The development of nano-drug delivery system has gone through the process of p...

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
Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/60A61K31/704A61P35/00C08F8/32C08F293/00C08F2/38
CPCA61K31/704A61K47/60A61K47/6907A61P35/00C08F2/38C08F8/32C08F2438/03C08F293/005
Inventor 孙勇赵明达樊渝江马孟城随俊慧张兴栋
Owner SICHUAN UNIV
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