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Mannan-containing ligand and preparation method and application thereof

A mannan and ligand technology, applied in the field of chemistry, can solve the problems of limited application of nano-carriers, toxic and side effects, lack of specific recognition performance, etc., and achieve the effects of concentrated particle size distribution, extended shelf life, and round and smooth surface morphology.

Inactive Publication Date: 2011-04-27
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the lack of specific recognition properties for target organs, tissues, and cells may lead to unexpected toxic side effects, which limits the application of nanocarriers.

Method used

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  • Mannan-containing ligand and preparation method and application thereof
  • Mannan-containing ligand and preparation method and application thereof
  • Mannan-containing ligand and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1. Synthesis of the graft polymer (Mannan-PE) of mannan and phosphatidylethanolamine:

[0050] Mannan (100 mg) was dissolved in sodium hydroxide solution (3 mol / L, 1 mL), and stirred for 10 minutes to make it alkaline. Chloroacetic acid (16%, 1.2 mL) was then added and stirred in an oil bath at 55°C for 7 hours, then hydrochloric acid (1 mol / L) was added to adjust the pH to 2-3 to obtain carboxymethylated mannan. After carboxymethylated mannan was dissolved in dimethyl sulfoxide (DMSO), phosphatidylethanolamine (5 mg) which was also dissolved in dimethyl sulfoxide was added under stirring, and dimethyl sulfoxide was added dropwise under ice-bath conditions. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl) (12 mg) dissolved in sulfone (adding an equimolar amount of triethylamine to it), stirred in an ice bath for one hours, then stirred at room temperature for 48 hours. Dimethyl sulfoxide was removed by rotary evaporation, the precipitate w...

Embodiment 2

[0053] Embodiment 2. Preparation of solid lipid nanoparticle suspension

[0054] Weigh 25 mg of stearic acid and 15 mg of lecithin, mix them and add 3 mL of acetone to ultrasonically dissolve them as the organic phase. Weigh 20 mg of cetyltrimethylammonium bromide (CTAB) and dissolve in 20 mL of double distilled water as the water phase. The organic phase was injected into the aqueous phase stirred at 600 r / min at a constant speed of 18 mL / h. Continue stirring at 400 r / min for 8 hours to completely volatilize the organic solvent, adjust the pH value to 7.2-7.4, and obtain a cationic solid lipid nanoparticle suspension.

Embodiment 3

[0055] Embodiment 3: Research on the physical and chemical properties of solid lipid nanoparticle suspension

[0056] Get the solid lipid nanoparticle suspension in Example 2 and drop it onto a copper grid covered with a carbon film, let it stand for 2 minutes, blot the suspension with filter paper, then add dropwise a mass concentration of 2% phosphotungstic acid for negative staining for 2 minutes , observe the morphology of the nanoparticles under a transmission electron microscope and take pictures. Another appropriate amount of nanoparticle suspension was taken, and after appropriate dilution, the average particle size and polydispersity were measured with a Zetasizer 3000 HS nanoparticle size analyzer. Then take an appropriate amount of nanoparticle suspension, and measure the zeta potential with a nanoparticle size analyzer after appropriate dilution.

[0057] The nanoparticles observed under the transmission electron microscope are spherical or quasi-spherical solid p...

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Abstract

The invention designs and synthesizes a graft polymer of mannan and phosphatidylethanolamine (PE) and the polymer is used as ligand and applied to the surface modification of nanocarrier. The invention belongs to the chemical technical field and is characterized in that the hydrophilic site of glycosyl, the hydrophobic site of lipid radical and the negative mannan ligand are prepared by chemosynthetic method with simple synthesis method and high yield; the products are applicable to the surface modification of nanocarrier of gene with positive ions of various carrier materials; because the mannan targets the mannose receptor on the surface of macrophage, the modified nanocarrier can react on the murine macrophage with low cytotoxicity, thus realizing the targeting transfection of macrophage of nanocarrier. The targeted graft polymer used as ligand is applicable to the surface modification of nanocarrier of gene with positive ions.

Description

technical field [0001] The invention relates to a mannan-containing ligand, a preparation method thereof and an application in nanocarrier surface modification, belonging to the field of chemical technology. Background technique [0002] Nanocarrier is a very popular non-viral carrier in recent years. Because of its safety, low toxicity, non-immunogenicity and extremely small particle size compared with viral vectors, nanocarriers have attracted more and more attention in the fields of basic scientific research and clinical medical research. However, the lack of specific recognition properties for target organs, tissues and cells may lead to unexpected toxic side effects, thus limiting the application of nanocarriers. [0003] The surface modification of nanocarriers to make them become modified nanocarriers with special ligands on the surface, so as to endow them with the ability to specifically recognize targets and actively target target cells and tissues, is the goal pu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/00C12N15/87A61K47/48A61K48/00A61K47/59C12N15/88
Inventor 张娜徐文方余汪洋刘瑜
Owner SHANDONG UNIV
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