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A kind of degradable polymer magnetic nanoparticles and preparation method thereof

A technology of magnetic nanoparticles and degrading polymers, applied in the direction of magnetism of organic materials/organic magnetic materials, drug combination, drug delivery, etc., can solve the problems of toxic side effects, weak interaction force, low transverse relaxation performance, etc. Good stability, high stability effect

Active Publication Date: 2020-10-13
SOUTHWEST UNIVERSITY FOR NATIONALITIES
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

However, with the in-depth research on polymer magnetic nanoparticles, it is found that there are still some defects that restrict the large-scale clinical application of magnetic nanoparticles in the process of realizing diagnosis and treatment:
[0003] (1) The polymer shell cannot be degraded
The technology of using polymer materials as shells to wrap magnetic nanoparticles to form polymer magnetic nanoparticles has the advantages of simple method and clear nanoparticle structure, but the formed polymer shells generally have no degradation function and are easy to occur in the human body. Aggregation, thus causing toxicity to liver, kidney and other organs (Fang C., Kievit F.M., Veiseh O., Stephen Z.R., Wang T., Lee D., Ellenbogen R.G., Zhang M. Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach. Journal of Controlled Release. 2012,162:233–241)
[0004] (2) Insufficient stability of nanoparticles
Due to the weak interaction between the drug and the polymer formed by this technical means, the loading stability of the drug is also poor, and more drugs are often released in advance in normal tissues and cells. Particles generally have toxic and side effects on normal tissue cells (Chen J., Shi M., Liu P., Ko A., Zhong W., Liao W., Xing M., M.Q. Reducible polyamidoamine-magnetic iron oxide self-assembled nanoparticles fordoxorubicin delivery. Biomaterials, 2014, 35:1240–1248)
[0005] (3) No targeting function, so that the polymer magnetic nanoparticles cannot be released accurately after drug loading
Although this technology has the advantage of simple preparation method, the polymer magnetic nanoparticles prepared by it have no targeting function, and the polymer magnetic nanoparticles cannot be effectively delivered into the targeted cells, and released to kill tumor cells.
Therefore, drug-loaded polymer magnetic nanoparticles are prone to aggregation in normal tissues and cells, and there is a risk of side effects (Shang Le, Zhou Qinghan. Preparation and Characterization of Multifunctional Magnetic Nano-Drug Carriers. Journal of Southwest University for Nationalities (Natural Science Edition) ),2016,42(5):531-537)
[0006] (4) Poor imaging effect
The polymer magnetic nanoparticles prepared by traditional technology, because the interaction force between the polymer material and the magnetic nanoparticles is weak (such as non-covalent bond forces such as hydrophobic bonds and hydrogen bonds), the content of the magnetic nanoparticles wrapped is relatively small , leading to the transverse relaxation properties (r 2 ) is low, and the contrast effect is not good, which affects the clinical application of polymer magnetic nanoparticles as magnetic contrast (Liu Y., Yang K., Cheng L., Zhu J., Ma X., Xu H., Li Y. , Guo L., Gu H., Liu Z. PEGylated FePt@Fe 2 o 3 core-shell magnetic nanoparticles: Potential theranostic applications and in vivo toxicity studies. Nanomedicine: Nanotechnology, Biology, and Medicine, 2013, 9:1077–1088)

Method used

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  • A kind of degradable polymer magnetic nanoparticles and preparation method thereof
  • A kind of degradable polymer magnetic nanoparticles and preparation method thereof
  • A kind of degradable polymer magnetic nanoparticles and preparation method thereof

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Effect test

Embodiment 1

[0042] FeCl with a molar ratio of 1:2 3 ·6H 2 O and FeSO 4 , add 50mL of deionized water to prepare a 0.7g / mL solution, blow in nitrogen and mechanically stir at 80°C, then add 5mL of concentrated ammonia water to react for 50min, then add 1mL of oleic acid, and continue to react for 6h. The obtained crude product is collected by a magnet, washed with deionized water, centrifuged, and dried to obtain the product ferroferric oxide nanoparticles.

[0043] The coupling agent containing double vinyl disulfide bond 130mg, DA 72mg, DOX 70mg, mPEG-NH 2 328mg, FA-PEG-NH 2 52 mg was mixed evenly, and at the same time, 50 μL of triethylamine was dissolved in 10 mL of DMSO to form a solution with a volume concentration of 0.5%, and then added dropwise to the above mixture, and reacted at 20°C for 20 hours under nitrogen protection. After the reaction, the crude product was washed and precipitated with ether, dissolved in deionized water, dialyzed, and freeze-dried to obtain a dark ...

Embodiment 2

[0046] FeCl with a molar ratio of 1:3 3 ·6H 2 O and FeSO 4 , add 50mL of deionized water to prepare a 0.5g / mL solution, blow in nitrogen and mechanically stir at 50°C, then add 4mL of concentrated ammonia water to react for 40min, then add 1mL of oleic acid, and continue to react for 4h. The obtained crude product is collected by a magnet, washed with deionized water, centrifuged, and dried to obtain the product ferroferric oxide nanoparticles.

[0047] The coupling agent containing double vinyl disulfide bond 50mg, DA20mg, DOX20mg, mPEG-NH 2 100mg, FA-PEG-NH 2 20 mg was mixed evenly, and at the same time, 80 μL triethylamine was dissolved in 10 mL DMSO to form a solution with a volume concentration of 0.8%, and then added dropwise to the above mixture, and reacted at 30°C for 48 hours under nitrogen protection. After the reaction, the crude product was washed and precipitated with ether, dissolved in deionized water, dialyzed, and freeze-dried to obtain a dark red solid...

Embodiment 3

[0050] FeCl with a molar ratio of 1:43 ·6H 2 O and FeSO 4 , add 50mL of deionized water to prepare a 1g / mL solution, blow in nitrogen and mechanically stir at 90°C, then add 1mL of sodium hydroxide solution to react for 30min, then add 3mL of oleic acid, and continue to react for 5h. The obtained crude product is collected by a magnet, washed with deionized water, centrifuged, and dried to obtain the product ferroferric oxide nanoparticles.

[0051] The coupling agent containing double vinyl disulfide bond 150mg, DA 100mg, DOX 100mg, mPEG-NH 2 500mg, FA-PEG-NH 2 100 mg was mixed evenly, and at the same time, 90 μL of triethylamine was dissolved in 10 mL of DMF to form a solution with a volume concentration of 0.9%, and then added dropwise to the above mixture, and reacted at 50°C for 36 hours under nitrogen protection. After the reaction, the crude product was washed and precipitated with ether, dissolved in deionized water, dialyzed, and freeze-dried to obtain a dark red...

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Abstract

The invention discloses a degradable polymer magnetic nanoparticle and a preparation method thereof. The preparation method utilizes a divinyl disulfide bond-containing compound as a coupling agent and comprises that dopamine, an antitumor drug group and a targeting functional group are connected to the main chain of the coupling agent through covalent bonds so that a degradable shell is prepared through polymerization, and the degradable shell chemically coats outer surfaces of ferroferric oxide nanoparticles so that dopamine on the degradable shell can be bonded to the surfaces of the ferroferric oxide nanoparticles through coordination bonds and the degradable polymer magnetic nanoparticle is formed. The polymer shell is degradable and can be stably bonded to the magnetic nanoparticles through coordination bonds. The degradable polymer magnetic nanoparticle has good drug loading stability and has a targeting function and good contrast effects.

Description

technical field [0001] The invention belongs to the technical field of degradable polymer magnetic nanoparticles and its preparation, and in particular relates to a method of wrapping a degradable polymer material in a magnetic nanoparticle shell as a drug carrier and a preparation method thereof, in particular to a method for wrapping a degradable polymer material in a magnetic nanoparticle shell. Degradable polymer material as drug carrier with targeting function and preparation method thereof. Background technique [0002] In recent years, based on Fe 3 o 4 The magnetic nanoparticles have the advantages of superparamagnetism and low cytotoxicity, and have been widely used in the integrated research of drug delivery (therapy) and magnetic resonance imaging (medical diagnosis). In order to improve the stability of magnetic nanoparticles, a technical solution generally adopted by those skilled in the art is to prepare polymer magnetic nanoparticles by wrapping a layer of p...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/60A61K47/54A61K31/704A61K49/18A61K49/12C08G81/00C08G83/00H01F1/42A61P35/00
CPCA61K9/0009A61K31/704A61K49/126A61K49/1833A61K49/186A61K49/1887C08G81/00C08G83/001H01F1/42
Inventor 周庆翰王秋月尚乐
Owner SOUTHWEST UNIVERSITY FOR NATIONALITIES
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