Preparation method of microgel based on shear force sensitivity and CD44 receptor targeting

A technology of CD44 and shear force, applied in the field of nanomaterials, can solve the problem of few and few mechanical stress-sensitive materials, achieve convenient diagnosis and treatment, low side effects, and good biocompatibility

Active Publication Date: 2020-01-10
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the field of biomedical carriers, there are very few researches and applications on mechanical stress-sensitive materials.

Method used

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  • Preparation method of microgel based on shear force sensitivity and CD44 receptor targeting
  • Preparation method of microgel based on shear force sensitivity and CD44 receptor targeting
  • Preparation method of microgel based on shear force sensitivity and CD44 receptor targeting

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Synthesis of amphiphilic polymer PAA-b-PEHA

[0032]

[0033] Under anhydrous and oxygen-free conditions, add 20mg CuCl and 36mg of 2,2-bipyridine to the reaction flask to complex to brick red, add 3ml tBA, 2ml 2-EHA and 2ml DMF respectively, and mix well, then heat to 80°C for 12h, ice The water bath terminates the reaction. Add 50ml CHCl 3 After filtering with neutral alumina, it was concentrated to 4ml by rotary evaporation, and PtBA-b-PEHA was prepared by precipitation in 1000ml methanol; PtBA-b-PEHA was completely dissolved in 10ml CHCl 3 , Add 1.5ml of TFA to the polymer solution, react at room temperature for 48h; after the reaction, add 100ml of CHCl to the reaction flask 3 Rotary evaporation to 5ml, repeat the above operation three times; Precipitate the concentrated solution in 1000ml methanol to obtain PAA-b-PEHA; figure 1 It can be seen that the assignment of the NMR spectrum H is correct.

Embodiment 2

[0034] Example 2: Synthesis of amphiphilic graft copolymer P(AA-g-HEMA)-b-PEHA

[0035]

[0036] Take 0.25g of PAA-b-PEHA dissolved in 50ml of THF, then add 80mg EDC and 155mg NHS respectively to continue activation for 60 minutes; finally add 3ml of HEMA to the reaction solution, 2 The reaction was kept in the dark for 24 hours; after the reaction, it was concentrated to 3~5ml by rotary evaporation, and precipitated in 1000ml methanol to prepare (PAA-g-HEMA)-b-PEHA; figure 2 It can be seen that the assignment of the NMR spectrum H is correct.

Embodiment 3

[0037] Example 3: Synthesis of hyaluronic acid hydrogel precursor (HAGMA)

[0038]

[0039] Dissolve 0.5g of sodium hyaluronate in 50-100ml of deionized water, mix 0.977g of DMAP and 1.093g of TBAB and add to the hyaluronic acid solution, stir at room temperature for 1h; add 3 to 5ml of GMA to the mixed solution, and protect it under N2 Under the conditions, react at room temperature for 48 hours; after the reaction, add NaCl to the reaction solution to a concentration of 5%, and then add methanol (methanol: water = 3:1, volume ratio); use a high-speed centrifuge to separate the white precipitate (speed 7000r / min), and repeat the above operation three times; Dissolve the white precipitate obtained in 300ml of deionized water, respectively dialyzed with 1mol / L NaCl aqueous solution and deionized water for 24h, the molecular weight cut-off of the dialysis bag is 10,000, to obtain HAGMA; The product is lyophilized, by image 3 It can be seen that the assignment of the NMR spectrum H...

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PUM

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Abstract

The invention discloses a preparation method of microgel based on shear force sensitivity and CD44 receptor targeting, and belongs to the technical field of nano materials. The preparation method comprises the following steps: synthesizing an amphiphilic polymer PAA-b-PEHA, synthesizing an amphiphilic graft copolymer P(AA-g-HEMA)-b-PEHA, synthesizing a hyaluronic acid hydrogel precursor HAGMA, andsynthesizing a double-response microgel HACBC with shear force response and CD44 receptor targeting. According to the prepared nano microgel, mechanical force sensitivity and CD44 receptor targetingare combined, so that an affected part can be more accurately targeted and a therapeutic drug is released at the affected part. In addition, the used raw materials are all degradable materials with good biocompatibility and low toxic and side effects, and the side effects on human bodies are extremely low.

Description

Technical field [0001] The invention belongs to the technical field of nanomaterials, and specifically relates to a dual-response smart microgel nano drug-carrying system capable of responding to the shear force at the thrombus in the blood vessel and targeting CD44 receptors. Background technique [0002] Atherosclerosis is a chronic inflammatory disease. Due to the continuous improvement of people's living standards, the incidence is increasing year by year. The biggest threat of atherosclerosis is the rupture of blood vessels caused by thrombus and unstable plaque, leading to cardiovascular and cerebrovascular complications, such as acute coronary syndrome (ACS) and stroke. In the past ten years, the drugs used to treat atherosclerosis mainly include aspirin, statins and other powerful antiplatelet drugs, as well as various drugs that reduce low-density lipoprotein (LDL) levels. In the further study of the pathological mechanism of atherosclerosis, it was found that a large n...

Claims

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Application Information

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IPC IPC(8): A61K9/06A61K47/36A61K47/32A61K31/366A61P7/02
CPCA61K9/06A61K47/36A61K47/32A61K31/366A61P7/02
Inventor 李亚鹏姚顺雨于艳辉刘顺李少静沈美丽武小东
Owner JILIN UNIV
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