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Preparation method of nano-drug and application of nano-drug in treatment of osteosarcoma

A drug and polymer technology, applied in the field of biomedicine, can solve the problems of inability to target tumor stem cells, limited anti-tumor effect, etc., and achieve the effect of high clinical application value and good biocompatibility

Active Publication Date: 2020-03-27
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0012]The latest research shows that Apatinib or GSK-J4 has the effect of inhibiting the growth of osteosarcoma tumor cells, but the pharmaceutical composition is hydrophobic and cannot target tumor stem cells , the antitumor effect has certain limitations

Method used

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  • Preparation method of nano-drug and application of nano-drug in treatment of osteosarcoma
  • Preparation method of nano-drug and application of nano-drug in treatment of osteosarcoma
  • Preparation method of nano-drug and application of nano-drug in treatment of osteosarcoma

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Experimental program
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Embodiment 1

[0041] The preparation of embodiment 1 polymer Cys-8E

[0042] 1. The preparation of polymer Cys-8E comprises the following steps:

[0043] Using triethylamine as an acid-binding agent, 10 mmol of sebacoyl chloride was dropped into a DMSO mixed solution in which equimolar L-cystine dimethyl dihydrochloride ((H-Cys-OMe)2·2HCl) had been dissolved. After stirring for 20 minutes, it was precipitated three times with 250 ml of cold diethyl ether, and reduced to dryness under a nitrogen atmosphere to finally obtain a white yellowish solid. It can be proved that the desired Cys-8E polymer is obtained by proton nuclear magnetic spectrum analysis of the polymer. The presence of disulfide bonds can be seen from the infrared spectrum.

Embodiment 2

[0044] Example 2 Preparation of a GSH-responsive blank nano drug-loading system

[0045] To prepare blank Cys-8E nanoparticles, dissolve Cys-8E in DMSO at a concentration of 20 mg / ml to form oil phase 1. Stabilizer DSPE-PEG2000 was dissolved in DMSO at a concentration of 4 mg / ml to form oil phase 2. Mix 1 and 2 phase oils in the same volume and add to deionized water stirred at a speed of 2000r / m. The volume ratio of the oil phase to the water phase is 1:9. Use an ultrafiltration tube with a molecular weight cutoff of 100,000Da to centrifuge three times to remove the free organic solution DMSO, and finally resuspend with PBS. The particle size of the drug-loaded nanoparticles detected by DLS was 70-90nm; the results of TEM detection showed that the nanoparticles were uniformly dispersed spherical structure.

Embodiment 3

[0046] Example 3 Preparation of a GSH-responsive dual-drug Apatinib and GSKJ4 nanosystem

[0047] When preparing the drug-loaded Cys-8E nanoparticles, Cys-8E was dissolved in DMSO to form oil phase 1 with a concentration of 20 mg / ml. Drugs Apatinib and GSKJ4 were dissolved in oil phase 1 at a mass ratio of 2:1, and the drug concentration was 9 mg / ml. Stabilizer DSPE-PEG2000 was dissolved in DMSO at a concentration of 4 mg / ml to form oil phase 2.

[0048] Take an appropriate volume of 1 and 2 phase oils and mix well so that DSPE-PEG2000 is about 20wt% of the total mass of Cys-8E, Apatinib and GSKJ4, and add it dropwise to deionized water stirred at a speed of 2000r / m. The volume ratio of the oil phase to the water phase is 1:9. Use an ultrafiltration tube with a molecular weight cutoff of 100,000Da to centrifuge three times to remove the free organic solution DMSO, and finally resuspend with PBS. DLS detected that the particle size of the drug-loaded nanoparticles was 100-15...

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Abstract

The invention discloses a preparation method of a nano-drug and application of the nano-drug in treatment of osteosarcoma. A Cys-8E material synthesized in the invention is good in biocompatibility and strong in drug entrapment capacity. After Apatinib and GSK-J4 are entrapped by a nano-carrier to prepare a nano-drug (NPJ4+Apa), then the nano-drug (NPJ4+Apa) can target a tumor site of osteosarcoma, and has the better drug delivery capability for osteosarcoma stem cells which cannot be acted by a traditional drug. The nano-drug NPJ4+Apa can induce apoptosis of the osteosarcoma stem cells, and the treatment effect of Apatinib and GSK-J4 is remarkably improved. Meanwhile, the nano-drug NPJ4+Apa can prevent Apatinib and GSK-J4 from acting on normal cells, so that the toxic and side effects ofApatinib and GSK-J4 are reduced. The nano-drug NPJ4+Apa has the advantages of targeting the osteosarcoma stem cells, being small in side effect and the like, and has a good application prospect and awide development space in the clinical field of osteosarcoma.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. More specifically, it relates to a preparation method of nano-medicine and its application in treating osteosarcoma. Background technique [0002] Osteosarcoma is the most common primary malignant bone tumor, accounting for about 15% of all bone tumors. year. At present, the treatment of osteosarcoma is mainly based on surgery combined with systemic chemotherapy. However, due to the lack of selectivity of traditional chemotherapy drugs, most of the drugs are concentrated in the area outside the tumor, so that the effective dose to reach the tumor is low, and it brings serious toxic side effects. , Moreover, multi-drug resistance to chemotherapy drugs and new treatment methods have not been standardized, and the clinical drug treatment of osteosarcoma is limited. [0003] How to improve the efficiency of chemotherapy, reduce tumor multi-drug resistance, and reduce the recurrence and metasta...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G69/42A61K31/519A61K31/4545A61K9/51A61P35/00
CPCC08G69/42A61K31/519A61K31/4545A61K9/5146A61P35/00A61K2300/00
Inventor 赵蔚吴钧王力
Owner SUN YAT SEN UNIV
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