Nanogel and nanogel drug carrier system both with smart response to tumor microenvironment

A nano-gel, responsive technology, applied in the field of polymer drug carriers, can solve the problems of slow pH responsiveness, time-consuming, and hindering anti-tumor effects.

Active Publication Date: 2017-06-09
HUAZHONG UNIV OF SCI & TECH
View PDF5 Cites 17 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the main strategy of hydrophilic-hydrophobic inversion nanomaterials is to rely on the fragmentation of pH-responsive chains to de-PEGylate, and the occurrence of such chemical reactions takes a lot of time, which leads to slow pH responsiveness and affects the anti-tumor effect of nano-medicines.
At the same time, the introduction of pH sensitivity not only requires a complicated chemical synthesis process, but also this process will introduce organic reagents, which may cause side effects
[0004] Due to the highly disordered vascular structure of...

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
  • Nanogel and nanogel drug carrier system both with smart response to tumor microenvironment
  • Nanogel and nanogel drug carrier system both with smart response to tumor microenvironment
  • Nanogel and nanogel drug carrier system both with smart response to tumor microenvironment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] (1) Accurately weigh 1.908g N-isopropylacrylamide (NIPAM), 0.262g sulfobetaine methyl methacrylate (SBMA) and 0.18ml N-methallylamine (MAA) and dissolve in 500ml In a three-necked bottle, dissolve with 200ml of ultrapure water, add 0.04g of sodium lauryl sulfate as a surfactant and 0.098g of a cross-linking agent N,N'-bisacrylcystamine, and mix by ultrasonic. Corresponding to the molar ratio of N-isopropylacrylamide, sulfobetaine methyl methacrylate and N-methallylamine is 85.7:4.8:9.5, cross-linking of N,N'-bisacrylcystamine The density is 2 mol%.

[0048] (2) Pass nitrogen to the above reaction system to remove residual oxygen in the mixed solution. Heating in a water bath under magnetic heating stirring, slowly raising the temperature to 70-75°C, then adding 0.1g of potassium persulfate to initiate the polymerization reaction

[0049] (3) After the solution became turbid, the reaction was continued for 4.5 h at 70-75° C. under a nitrogen atmosphere.

[0050] (4) T...

Embodiment 2

[0052] (1) Accurately weigh 2.012g of N-vinylisobutylamide, 0.250g of carboxybetaine methacrylate and 0.20g of methacryloyloxyethyltrimethylammonium chloride and dissolve them in a 500ml three-necked bottle , dissolved in 200ml ultrapure water, and added 0.04g sodium lauryl sulfate as a surfactant and 0.098g cross-linking agent N,N'-bisacryloylcystamine, and ultrasonically mixed. The molar ratio of N-vinylisobutylamide, carboxybetaine methacrylate and methacryloyloxyethyltrimethylammonium chloride is 89.6:5.5:4.9, N,N'-bisacryloyl Cystamine has a crosslink density of 1.9 mol%.

[0053] (2) Pass nitrogen to the above reaction system to remove residual oxygen in the mixed solution. Heating in a water bath under magnetic heating stirring, slowly raising the temperature to 70-75°C, then adding 0.1g of potassium persulfate to initiate the polymerization reaction

[0054] (3) After the solution became turbid, the reaction was continued for 4.5 h at 70-75° C. under a nitrogen atmos...

Embodiment 3

[0057] (1) Accurately weigh 1.739g of N-vinylcaprolactam, 0.434g of 2-methacryloyloxyethylphosphorylcholine and 0.202g of N,N'-dimethylallylamine and dissolve them in a 500ml three-necked bottle , dissolved in 200ml ultrapure water, and added 0.04g sodium lauryl sulfate as a surfactant and 0.05g crosslinking agent diallyl disulfide, and ultrasonically mixed. The molar ratio of N-vinylcaprolactam, 2-methacryloyloxyethylphosphorylcholine and N,N'-dimethylallylamine is 74.5:9.0:14.5, diallyl disulfide The crosslink density was 2.1 mol%.

[0058] (2) Pass nitrogen to the above reaction system to remove residual oxygen in the mixed solution. Heating in a water bath under magnetic heating stirring, slowly raising the temperature to 70-75°C, then adding 0.1g of potassium persulfate to initiate the polymerization reaction

[0059] (3) After the solution became turbid, the reaction was continued for 4.5 h at 70-75° C. under a nitrogen atmosphere.

[0060] (4) The obtained reaction s...

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
Surface chargeaaaaaaaaaa
Surface chargeaaaaaaaaaa
Login to view more

Abstract

The invention provides a nanogel with hydrophilic and hydrophobic reversal, charge reversal and intracellular redox responsiveness on the basis of pH regulation. The nanogel is prepared by cross-linking of thermo-sensitive monomer with controllable radical polymerization, amphoteric ionic monomer and amido-containing pH sensitive monomer through a disulfide-bond-containing cross-linking agent. The invention further provides a nanogel drug carrier system with smart response to tumor microenvironment and its preparation method. On the condition of blood pH 7.4, the nanogel is in a hydrophilic swelling state that is favorable for avoiding being phagocytosed by the reticuloendothelial system (RES) and accordingly, the nanogel has blood long circulation capacity; on the condition of tumor tissue subacidity, the state of the nanogel is reversed into a hydrophobic shrinking state that is favorable for the nanogel to realize effective concentration, depth penetration and be absorbed effectively by tumor cells on the tumor location. Besides, in the intracellular lysosome environment, negative charge of the nanogel is reversed into positive charge, which is favorable for the nanogel to escape from the lysosome; and then the nanogel releases drugs responsively in cytoplasm high-GSH environment, thereby achieving a good tumor inhibition effect.

Description

technical field [0001] The invention relates to the technical field of polymer drug carriers, in particular to a nanogel and a nanogel drug-carrying system that respond intelligently to the tumor microenvironment with pH-regulated hydrophilicity-hydrophobicity reversal, charge reversal, and intracellular redox responsiveness. and their preparation methods. Background technique [0002] Nano-drug delivery system is widely used in tumor therapy because of its EPR effect, which can improve tumor targeting, enhance the efficacy of chemotherapy drugs and reduce side effects. The anti-tumor nano-drug delivery system needs to pass through multiple physiological barriers in the body when reaching the target site through intravenous injection. In order to break through these physiological barriers, the ideal nano-drug delivery system must have long circulation in the blood, effective enrichment of tumor sites, deep tumor penetration, The ability to be effectively taken up by tumor c...

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): C08F216/14C08F220/34C08F220/36C08F220/38C08F220/54C08F222/38C08F222/40C08F226/02C08F226/06C08F228/02C08F230/02A61K9/06A61K47/32A61K31/704A61K31/337A61P35/00
CPCA61K9/0002A61K9/06A61K31/337A61K31/704A61K47/34C08F216/14C08F220/54C08F226/02C08F226/06C08F230/02C08F228/02C08F220/387C08F222/385C08F220/365C08F220/34C08F222/408
Inventor 甘璐王芹杨祥良杨昊李福英
Owner HUAZHONG UNIV OF SCI & TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap