Drug-loaded hybrid nanoparticles and preparation method thereof

A technology of hybrid nanoparticles and drug loading, which is applied in the field of biomedical materials, can solve the problems of low drug loading, slow drug release, poor anti-tumor effect and safety, and achieve good biocompatibility and no toxic side effects , high safety effect

Active Publication Date: 2020-03-10
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Aiming at the above-mentioned deficiencies in the prior art, the present invention provides a drug-loaded hybrid nanoparticle and a preparation method thereof, which can effectively solve the problems of low drug-loading capacity, slow drug release speed, anti-tumor effect and safety of existing drug-loaded nanoparticles. sex problem

Method used

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  • Drug-loaded hybrid nanoparticles and preparation method thereof
  • Drug-loaded hybrid nanoparticles and preparation method thereof
  • Drug-loaded hybrid nanoparticles and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1 Preparation of azide triketal compound

[0050] The schematic diagram of the preparation route of the azide triketal compound is shown in figure 2 , Specifically: Weigh a small amount of 2,2-dimethoxy-phenylacetophenone into a round bottom flask, heat it quickly outside to melt, then add pentaerythritol triallyl ether and thioglycerol, stir to dissolve Then, the reaction was stirred for 1 hour under a 365nm UV lamp, then a small amount of methanol was added to dissolve, and then a large amount of petroleum ether was added. After stirring and standing, the methanol layer was taken and the solvent was removed to obtain Intermediate 1; Intermediate 1 and 2,2-Dimethoxy Mix with propyl propane, slowly add p-toluenesulfonic acid hydrate in small amounts several times, mix and stir at 30°C-40°C for 12h, add triethylamine, continue the reaction for 0.5h, and separate by column chromatography (V Petroleum ether :V Ethyl acetate =4:1), finally remove the solvent to obta...

Embodiment 2

[0052] Example 2 Preparation of propargylamine modified heparin sodium

[0053] Dissolve heparin sodium, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide in water, add propargylamine and adjust the pH of the solution to 6 7. React at room temperature for 24 hours, dialyzed with deionized water for 72 hours and freeze-dry; among them, heparin sodium, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, N-hydroxysuccinyl The mass ratio of imine to propargylamine is 1:0.56:0.34:0.029.

[0054] Dissolve the resulting product in D 2 O, do 400MHz 1 H-NMR scan, see the results Figure 5 .

Embodiment 3

[0055] Example 3 Propargylamine modified heparin sodium grafted azide triketal compound

[0056] See the preparation route of propargylamine modified heparin sodium grafted azide triketal compound image 3 , Specifically: heparin sodium modified by propargylamine, azide triketal compound, copper sulfate pentahydrate and sodium ascorbate in a mass ratio of 1:1.5:0.125:0.8 miscible in DMSO, under the protection of nitrogen at 40 Reaction at ℃ for 24h, DMSO dialysis for 72h, then water dialysis for 72h to remove organic solvent, and freeze-drying.

[0057] Dissolve the resulting product in D 2 O do 400M 1 H-NMR scan, nuclear magnetic spectrum such as Image 6 Shown.

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Abstract

The invention discloses a drug-loaded hybrid nanoparticle. A preparation method of the drug-loaded hybrid nanoparticle comprises the following steps of (1) preparing an azide triacetone compound, (2) preparing propargylamine modified heparin sodium, (3) grafting propargylamine modified heparin sodium into the azide triacetone compound, and (4) preparing the drug-loaded hybrid nanoparticle. According to the drug-loaded hybrid nanoparticle, natural polymer heparin serves as a framework material of the nanoparticle, and consists of the drug-loaded hybrid nanoparticle which has good biosafety and is prepared by a specific preparation process; the particle size of the drug-loaded hybrid nanoparticle is within an EPR (enhanced permeability and retention) effect range; passive targeting can be realized; and high-selectivity rapid drug release of the nanoparticle in a tumor cell can be realized by the responsivity in an overheating environment. Therefore, the prepared drug-loaded hybrid nanoparticle has the characteristics of good biocompatibility, high safety, no toxic or side effect and the like.

Description

Technical field [0001] The invention belongs to the technical field of biomedical materials, and specifically relates to a drug-loaded hybrid nano particle and a preparation method thereof. Background technique [0002] Cancer is a serious threat to human health and life in the world today. Common treatments for cancer include surgery, chemotherapy, and radiotherapy. Among them, doxorubicin (DOX) is an anthracycline anti-tumor drug, which has a broad spectrum of malignant tumor treatment effects and has been approved for clinical use. It mainly enters the cell through the cell membrane and acts on DNA to kill cancer cells. However, DOX is more toxic and has obvious side effects. Therefore, drug carrier systems such as nanoparticles and other drug carrier systems for anti-tumor research have received widespread attention and research in order to achieve safety Stable, effective targeted release of drugs and accurate treatment effect. The development of a stable, safe, effective...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/14A61K31/704A61K47/36A61K47/04A61K41/00A61P35/00C08B37/10
CPCA61K9/143A61K9/146A61K31/704A61K41/0052C08B37/0075
Inventor 易强英康珂马瑾顾忠伟
Owner SICHUAN UNIV
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