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Novel polyester compound, nano-drug taking novel polyester compound as carrier and application of nano-drug

A nano-drug and compound technology, applied in the field of biomedicine, can solve the problems of large side effects, poor targeting, and inability to inhibit osteosarcoma stem cells, etc., and achieve high clinical application value and good biocompatibility

Active Publication Date: 2020-10-13
CHANGZHI MEDICAL COLLEGE
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem to be solved by the present invention is to overcome the defects and deficiencies of the above-mentioned existing Apatinib such as poor targeting, large side effects and inability to inhibit osteosarcoma stem cells, provide a new type of nano drug, and realize the drug 8P4-Apa by nanoprecipitation method , to prepare a pH-responsive nano-drug loading system, and has the application prospect as 8P4-Apa nano-drug

Method used

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  • Novel polyester compound, nano-drug taking novel polyester compound as carrier and application of nano-drug
  • Novel polyester compound, nano-drug taking novel polyester compound as carrier and application of nano-drug

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 Preparation of a pH-responsive drug-loaded 8P4-Apa nanosystem

[0048] (1) When preparing drug-loaded 8P4 nanoparticles, 8P4 was dissolved in DMSO to form oil phase 1 with a concentration of 40 mg / mL. Apatinib drug was dissolved in oil phase 2 in DMSO at a drug concentration of 10 mg / mL. Stabilizer DSPE-PEG 2000 was dissolved in DMSO at a concentration of 20 mg / mL to form oil phase 3.

[0049] (2) Take an appropriate volume of 1, 2, and 3 oil phases and mix them well so that DSPE-PEG 2000 is 8P4, about 40 wt% of the total mass of Apatinib, and add it dropwise to deionized water stirred at a speed of 2000r / m. The volume ratio of oil phase to water phase is 1:6. 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 100-150nm; TEM images showed that the nanoparticles were ...

Embodiment 2

[0051] The drug delivery ability of embodiment 2 polymer 8P4

[0052] Fluorescent substance coumarin 6 (C 6 , 2.0ug / mL) loaded into 8P4 nanoparticles to obtain 8P4-C 6 nanoparticles.

[0053] (1) 143B (ATCC number HCC-1143, human-derived epithelial-like adherent growth) and SJSA1 cells (ATCC number CRL-1469, human-derived, epithelial-like adherent growth) in the logarithmic growth phase were treated with trypsin Digested, blown into single cell suspension, counted, inoculated into 6-well culture plate, 1.5×10 per well 5 cells. Cultivate in the incubator for 24 hours. After the cells adhere to the wall, add simple C 6 Solution and 8P4-C 6 Solutions were co-incubated at 37°C for 1 hour, fixed with 4% paraformaldehyde and stained with DAPI. Fluorescence intensity was recorded by fluorescence microscope and flow cytometer.

[0054] (2 Digest the 143B and SJSA1 cells in the logarithmic growth phase with trypsin, blow them into a single cell suspension, count them, inoculate ...

Embodiment 3

[0059] Example 3 Comparison of the effects of 8P4-Apa nanomedicine on the proliferation of osteosarcoma cells.

[0060] Through the cell viability test, the effects of different concentrations of 8P4-Apa nanoparticles and free Apatinib on the proliferation of osteosarcoma cells and the formation of tumor spheres by osteosarcoma stem cells were detected.

[0061] (1) The 143B and SJSA1 cells in the exponential growth phase were digested with trypsin, blown into a single cell suspension, counted, and inoculated into a 96-well culture plate. After culturing in the incubator for 24 hours, after the cells adhered to the wall, different concentrations of 8P4-Apa nanoparticles and Apatinib free drug were added. After culturing in the incubator for 48 hours, the cell viability was evaluated according to the instructions of the CellTiter-Glo Luminescent Cell Viability Assay Kit.

[0062] (2) The 143B and SJSA1 cells in the logarithmic growth phase were inoculated in a low-adhesion 96-w...

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Abstract

The invention discloses a novel polyester compound, a nano-drug taking the novel polyester compound as a carrier, and application of the nano-drug. According to the novel polyester compound, the nano-drug taking novel polyester compound as the carrier and the application of the nano-drug, a nano material 8P4 encapsulates a compound Apatinib, so that the nano-drug (8P4-Apa) can be prepared, and then the nano-drug (8P4-Apa) can target a tumor site of osteosarcoma; in addition, the nano-drug has good drug delivery capability on the stem cells of the osteosarcoma on which traditional drugs just exert poor effects; the treatment effect of the compound Apatinib is remarkably improved; the apoptosis of the stem cells of the osteosarcoma is induced; the nano material does not have obvious cytotoxicity under the application concentration; and meanwhile the toxic and side effects of the Apatinib on normal cells can be reduced through a nano drug delivery system. The nano-drug 8P4-Apa has the advantages of capability of targeting the osteosarcoma, small side effect and the like, and has a good application prospect and a wide development space in the field of clinical treatment of the 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 a highly malignant bone tumor with a relatively high incidence in adolescents or children under the age of 20. The current clinical treatment methods include surgical resection and combined chemotherapy with various cytotoxic drugs after surgery. Examples include doxorubicin, cisplatin, ifosfamide, and methotrexate. About 70% of patients can be cured, but for patients with advanced metastasis and recurrence of osteosarcoma, the clinical treatment options are limited. [0003] Angiogenesis is crucial for tumor growth, invasion and metastasis. Osteosarcoma tissue promotes angiogenesis by generating and releasing various pro-angiogenic factors, among which vascular endothelial growth factor is a very important one. At present, the a...

Claims

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Application Information

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IPC IPC(8): C08G69/44C07C229/36C07C227/18A61K9/14A61K47/34A61K31/444A61P35/00
CPCC08G69/44A61K9/146A61K31/444A61P35/00C07C229/36C07C227/18
Inventor 吴钧赵蔚李翔宇
Owner CHANGZHI MEDICAL COLLEGE
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