Glucan-based nanogel and preparation method and application thereof

A nano-gel, dextran-based technology is applied in the field of dextran-based nanogel and its preparation to achieve the effects of reducing toxic side effects, improving anti-tumor effect, and reducing tumor recurrence rate

Active Publication Date: 2019-07-30
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The Chinese Invention Patent Application Publication No. 106902383A discloses a glycerol methacrylate-modified glucose nanogel hemostatic material, which has excellent hemostatic effects on traumatic bleeding and internal bleeding in organs such as the liver, and is a good new type of hemostatic material. Hemostatic agent, which has good application prospects in clinical trauma, but the nanomaterial has no bioresponsive degradation in vivo

Method used

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  • Glucan-based nanogel and preparation method and application thereof
  • Glucan-based nanogel and preparation method and application thereof
  • Glucan-based nanogel and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] (1) Synthesis of Dextran Derivative I Modified by Vinyl Ether Acrylate

[0048] Dimethyl sulfoxide was distilled to remove water in advance for later use. Dextran with a molecular weight of 20,000 was dissolved in ultrapure water and freeze-dried for later use. Weigh 1.25g of lyophilized dextran, add 65mL of anhydrous dimethyl sulfoxide and properly heat up to dissolve it, vacuumize for 10 minutes to remove water and oxygen, and add 125mg of p-toluenesulfonic acid ( PSTA) and 1 mL of vinyl ether acrylate. After the whole system was magnetically stirred and reacted for 6 hours under the condition of anhydrous and oxygen-free normal temperature, 2-3 drops of triethylamine were added to quench the reaction. The reaction solution was transferred to methanol for dialysis overnight, methanol was removed by rotary evaporation, the remaining reaction solution was added dropwise to a sufficient amount of glacial ether to precipitate, and the precipitated white solid particles ...

Embodiment 2

[0057] Example 2 Acid degradation behavior verification of nanogel

[0058] Take 2mL of 1.0mg / mL dextran-based nanogel prepared in the same batch, divide it into two parts, place 1mL each in a dialysis bag with a molecular weight cut-off of 3500, and place them in 20mL buffer media with different pH, 37±0.5 Under shaking at ℃, samples were taken at 0h, 1h, 3h, 7h, 24h, 48h, and 72h to detect the particle size of the sample, and the results were as follows image 3 As shown in (a), it was found that the particle size of the dextran-based nanogel remained unchanged in the buffer solution of pH 7.4, and it was still uniform and stable for 72 hours, while in the buffer solution of pH 5.0, the system was chaotic and disintegrated after 7 hours Degradation flocculation occurred, which evidenced that the acid-responsive acetal groups were hydrolyzed in weak acid, degrading the gel network.

Embodiment 3

[0059] Example 3 Doxorubicin In Vitro Acid Response Release Experiment

[0060] Taking doxorubicin-loaded dextran-based nanogel (dosing amount 0.05:1) as an example, the acid-responsive release behavior of the dextran-based nanogel in vitro was studied. Take 2mL of dextran-based nanogels loaded with doxorubicin at 1mg / mL prepared in the same batch (the entrapment efficiency is 35.56% as measured by the ultraviolet standard curve method), divide into two, and each 1mL solution is placed in the molecular weight cut-off In the dialysis bag of 3500, respectively put in the dissolution container filled with 20mL dissolution medium, avoid light, and carry out the in vitro release test of doxorubicin at the medium temperature of 37±0.5°C. According to the set time interval 0h, 0.5h, 1h, 2h, 3h, 4h, 6h, 17h, 24h, take out 2mL of the release solution outside the dialysis bag, and add the same volume of blank dissolution medium, and measure the doxorubicin in the release solution by flu...

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Abstract

The invention discloses a glucan-based nanogel. Glucan is taken as a framework material, vinyl ether acrylate modification is carried out to obtain a glucan derivative I, then based on the glucan derivative I, sulfydryl modification and carboxyl modification are carried out respectively to obtain a glucan derivative II and a glucan derivative III, and the glucan derivative II and the glucan derivative III are mixed for a Michael addition reaction to obtain the glucan-based nanogel. Compared with the prior art, the obtained glucan-based nanogel contains acid-sensitive acetal groups, targeted release is achieved by utilizing the enhanced permeation and retention (EPR) of a solid tumor and the meta-acidic microenvironment at a tumor site, completely different antitumor strategies of two mechanisms comprising the chemotherapy and photodynamic therapy are combined, through the synergistic effect, the antitumor effect is improved, and the toxic and side effects of a chemotherapy drug are effectively reduced.

Description

technical field [0001] The invention belongs to the technical field of antitumor drug carriers, and in particular relates to a dextran-based nanogel and its preparation method and application. Background technique [0002] The indiscriminate damage of traditional small molecule chemotherapy drugs to normal tissues and the multidrug resistance of tumors limit their clinical effects. Doxorubicin hydrochloride is a classic broad-spectrum anti-tumor drug in clinical practice. It mainly causes abnormal cell growth and eventually death by interfering with the function of DNA. It is often used in combination with other chemotherapy drugs. Its common toxic and side effects include hair loss, bone marrow suppression, vomiting, rash and oral inflammation, etc. Long-term use can lead to severe cardiotoxicity, so the clinical dose needs to be strictly controlled, which limits its application and anti-tumor effect. The many defects of traditional chemotherapy have promoted the research ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/36A61K41/00A61K31/704A61P35/00C08J3/075C08J3/24C08B37/02C08L5/02
CPCA61K9/06A61K31/704A61K41/0057A61K47/36A61P35/00C08B37/0021C08J3/075C08J3/246C08J2305/02A61K2300/00
Inventor 陈维徐文博钱红亮戴琳黄德春王志祥
Owner CHINA PHARM UNIV
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