A kind of alendronic acid-functionalized polyethylene glycol-modified nanoparticles and preparation method thereof

A technology of alendronic acid and polyethylene glycol, applied in the field of polyethylene glycol modified nanoparticles and their preparation, can solve the problems of many operation steps, unfavorable clinical application, high cytotoxicity of cationic liposomes, etc. time, low cost

Active Publication Date: 2016-08-24
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, in the preparation method of the LCPII system, there are many operating steps, and there are many factors affecting the transfection efficiency. The cationic liposomes used at the same time have high cytotoxicity, and the phospholipid materials are expensive, which is not conducive to future clinical applications.

Method used

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  • A kind of alendronic acid-functionalized polyethylene glycol-modified nanoparticles and preparation method thereof
  • A kind of alendronic acid-functionalized polyethylene glycol-modified nanoparticles and preparation method thereof
  • A kind of alendronic acid-functionalized polyethylene glycol-modified nanoparticles and preparation method thereof

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preparation example Construction

[0069] The chemical reaction equation of the preparation process of compound D1 of the present invention is exemplified as follows:

[0070]

[0071] The chemical reaction equation of the preparation process of compound D2 of the present invention is exemplified as follows:

[0072]

[0073]

[0074] The chemical reaction equation of the preparation process of compound D3 of the present invention is exemplified as follows:

[0075]

[0076]

[0077] Preferably, the soluble calcium salt solution is selected from one or more of calcium chloride solution, calcium nitrate solution and calcium bromide solution.

[0078] Preferably, the phosphate solution is selected from one or more of disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium phosphate, potassium dihydrogen phosphate and diammonium hydrogen phosphate, and the carbonate solution is selected from potassium carbonate One or more of sodium carbonate and sodium bicarbonate.

[0079] Preferably, the...

Embodiment 1

[0082] A preparation method of alendronic acid functionalized polyethylene glycol modified nanoparticles, comprising the following steps:

[0083] (1) Preparation of Alendronic Acid Functionalized Polyethylene Glycol

[0084] Take compound A with a polyethylene glycol molecular weight of 2000 Daltons, and dissolve it in the organic solvent tetrahydrofuran (THF) to prepare a solution containing compound A;

[0085] Compound A:

[0086] Take a glutamic acid solution with a pH value of 7.5, add the glutamic acid to the compound A in a ratio of 1.5:1 to the solution containing compound A, react at room temperature for 10 h, and then use 0.2N hydrochloric acid Adjust the pH value of the mixed solution to 4.5, extract 6 times with chloroform, take the organic phase, dry it with anhydrous sodium sulfate, concentrate under reduced pressure, and then add it dropwise to cold diethyl ether under stirring, let stand, collect the precipitate, and dry to obtain compound B1;

[0087] Com...

Embodiment 2

[0099] (1) Preparation of four alendronic acid functionalized monomethyl ether polyethylene glycols

[0100] Compounds B1 and C1 were prepared according to the method in Example 1.

[0101] Take a glutamic acid solution with a pH value of 7.5, add it to the solution containing compound C1 according to the molar ratio of the glutamic acid and the carboxyl group of the compound B1 at a ratio of 3:1, react at room temperature for 8 hours, and then adjust the mixing The pH value of the solution was 2.5, and then extracted 6 times with chloroform, and the organic phase was dried with anhydrous sodium sulfate, concentrated under reduced pressure, added dropwise into cold diethyl ether under stirring, left to stand, the precipitate was collected, and dried to obtain compound B2;

[0102] Compound B2:

[0103] Dissolve the compound B2 in the organic solvent tetrahydrofuran, N,N-dimethylformamide, dioxane, chloroform or dichloromethane, add N-hydroxysuccinimide and 1-ethyl-(3 -Dime...

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Abstract

The invention provides an alendronic acid-functionalized polyethylene glycol-modified nanoparticle, the nanoparticle is calcium phosphate particle or calcium carbonate particle coated with a target delivery object, and the target delivery object is selected from DNA, siRNA, protein For macromolecule drugs or small molecule chemical drugs, polyethylene glycol functionalized with alendronic acid is covered on the surface of nanoparticles, and the particle size of nanoparticles modified with polyethylene glycol functionalized with alendronic acid is 20-50 nm. The alendronic acid-functionalized polyethylene glycol-modified nanoparticles have a small particle size, and polyalendronic acid-polyethylene glycol can firmly cover the surface of the phosphate-gene particle, thereby effectively and stabilizing the nanoparticles for a long time , prolong the time of internal circulation, low cost, low toxicity, safe and effective. The invention also provides a preparation method of the alendronic acid-functionalized polyethylene glycol-modified nanoparticles.

Description

technical field [0001] The invention relates to the field of non-viral gene delivery systems, in particular to an alendronic acid-functionalized polyethylene glycol-modified nanoparticle and a preparation method thereof. Background technique [0002] Gene therapy offers a promising treatment for some major diseases. Since the gene therapy clinical trials began in 1990, only one or two gene therapy drugs have been approved for marketing. The main reason is the lack of stable gene expression and safe and efficient gene delivery vectors. [0003] Calcium phosphate is an excellent non-viral gene carrier with good tissue compatibility and absorption. The particle size obtained by the common calcium phosphate-gene co-precipitation method is larger than 100nm, which is difficult to control, has poor stability, and is difficult to be used for in vivo transfection. [0004] The Chinese patent application with publication number 101829330A discloses a calcium phosphate composite nan...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K48/00A61K9/16A61K47/34
Inventor 陈钏王志勇唐征乐何成宜陈志英
Owner SHENZHEN INST OF ADVANCED TECH
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