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Multi-response core-shell structure nanogel, and preparation method and application thereof

A technology of nanogel and core-shell structure, applied in the field of multi-response core-shell structure nanogel and its preparation, can solve the problems of inability to meet long-term and stable anti-tumor treatment needs, comprehensive treatment failure, etc., to reduce drug leakage, The preparation process is simple and easy, and the raw materials are easy to obtain

Pending Publication Date: 2021-10-01
JINLING INST OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, drug resistance to chemotherapy is a major problem in the treatment of malignant tumors today, and it is also an important reason for the failure of comprehensive therapy.
The current drug-carrying system loaded with a single anti-tumor drug has been found in countless clinical applications that drug resistance is prone to occur in patients, which cannot meet the needs of long-term and stable anti-tumor treatment. Designing multiple drugs in one drug delivery system has synergistic effects and can Reduce the dose and side effects of delivered drugs, enhance the therapeutic effect of tumors, and at the same time ensure the effective delivery of drugs and avoid premature clearance and excretion of drugs

Method used

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  • Multi-response core-shell structure nanogel, and preparation method and application thereof
  • Multi-response core-shell structure nanogel, and preparation method and application thereof
  • Multi-response core-shell structure nanogel, and preparation method and application thereof

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Embodiment 1

[0067] In order to solve the above problems, this embodiment provides a method for preparing a multi-response core-shell nanogel, which specifically includes the following steps:

[0068] Preparation of step 1 nanogel aqueous solution: prepare P(MAA- co -NIPAM) nanogel process is as follows: 300 mg of methacrylic acid (MAA), 100 mg of N-isopropylacrylamide (NIPAM), 60 mg of crosslinker N,N'-bis(acryloyl) Cystamine (BACy) and 8 mg of initiator AIBN were dissolved in 40 mL of acetonitrile solution (monomer concentration 1.0 wt%), and sonicated for 30 min to promote their dissolution. React at 95°C for 2 h. The reaction liquid was placed in a centrifuge tube, and the solid matter was separated by ultracentrifugation (12,000 rpm, 5 min), and the obtained microspheres were separated and purified by ultrasonic cleaning three times with acetonitrile solvent. Representative nanogel P(MAA- co -NIPAM) transmission electron microscope picture as figure 1 As shown, it can be seen th...

Embodiment 2

[0070] Preparation of iron ion cross-linked nanogel core

[0071] In a 100 mL round-bottomed flask, add 40 mL of acetonitrile solution, 500 mg of acrylic acid, 60 mg of iron trimethacrylate, 15 mg of AIBN (initiator), ultrasonically disperse for 10 min, heat the oil bath to 100 °C, and place in the flask Keep the reflux state with a condenser tube above, and react for 2 h. The reaction product was centrifuged (12,000 rpm, 5 min) to remove the supernatant and washed with ethanol for three times to obtain a nanogel. The Fourier transform infrared spectrum of the nanogel is shown in figure 2 shown. Of which 1643cm -1 The absorption peak at belongs to the stretching vibration absorption peak of amides. at 1520 cm -1 and 1374 cm -1 Typical metal carboxylate bands can be observed at , indicating the successful preparation of nanogels.

Embodiment 3

[0073] Preparation of core-shell nanogels

[0074] Chitosan-coated nanogel: Take 5 mL of the P(MAA-BACy) nanogel solution (mass concentration 50 mg / mL) prepared in Example 1 and put it in a 25 mL beaker for later use, weigh 20 mg of chitosan Dissolved in an aqueous solution of acetic acid with a concentration of 0.5-3% (more preferably 1%-2.5%, more preferably 2%), prepared into an aqueous solution of chitosan, and controlling the mass fraction of chitosan to 0.5-5wt%, more preferably It is 1.5~4wt%, more preferably 2.5wt%. At room temperature, add the chitosan aqueous solution dropwise to the nanogel aqueous solution, and the dropping time is 30-120 min, more preferably 50-100 min, more preferably 70 min. After the dropwise addition, continue to stir and react for 1-6 h (more preferably 2-5 h, more preferably 3.5 h) to separate the precipitate by high-speed centrifugation; wash repeatedly with ethanol and water several times to obtain the chitosan-coated nanogel.

[0075] P...

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Abstract

The invention discloses a multi-response core-shell structure nanogel, and a preparation method and application thereof, and belongs to the technical field of gel preparation. The method specifically comprises the following steps: 1, preparing a nanogel aqueous solution by a reflux precipitation polymerization method; 2, coating the outer surface of the nanogel core with chitosan to obtain chitosan-coated nanogel; and 3, coating the outer surface of chitosan with a hyaluronic acid shell layer to obtain the core-shell mechanism nanogel. The nanogel core is coated with the chitosan and the hyaluronic acid, the nanogel with a core-shell structure is prepared, and the obtained nanogel has temperature / pH / reduction multiple stimulation responsiveness. The coated hyaluronic acid shell layer can be specifically combined with a CD44 receptor on the surface of cancer cells, so that the nanogel can specifically target tumor cells.

Description

technical field [0001] The invention belongs to the technical field of gel preparation, and in particular relates to a multi-response core-shell structure nano gel and its preparation method and application. Background technique [0002] Nanogel refers to hydrogel nanoparticles formed by physical or chemical cross-linking with a size in the range of 1-1000 nm. Therefore, nanogel has the dual characteristics of hydrogel and nanoparticle at the same time. It is easy to be swallowed by cells, easy to penetrate various protective membranes in the human body, and has the advantages of good stability and high drug loading efficiency. It has been widely used in recent years. In the fields of medical diagnosis, sensing and drug release. Traditional nanogel preparation methods, such as conventional emulsion polymerization, miniemulsion polymerization, dispersion polymerization, etc., have a long reaction time, and stabilizers or emulsifiers need to be added during the preparation pr...

Claims

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Application Information

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IPC IPC(8): B01J13/00A61K9/06A61K31/704A61K33/243A61K47/36A61P35/00B82Y5/00B82Y40/00
CPCB01J13/0065A61K9/06A61K47/36A61K33/243A61K31/704A61P35/00B82Y5/00B82Y40/00A61K2300/00
Inventor 王昭王小美叶超宇沈玉琳徐贝贝
Owner JINLING INST OF TECH
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