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Preparation method and application of polycarbonate drug-loaded nano chemosensitizer based on nitric oxide

A technology of nitric oxide and drug-loaded nanometers, applied in nanotechnology, nanotechnology, nanomedicine, etc., to achieve strong drug-loading capacity, reduce toxic and side effects, and have small toxic and side effects

Pending Publication Date: 2021-11-23
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far, there are few related reports on whether nanomaterials can be used synergistically through both extrinsic sensitization and intrinsic sensitization to improve the effect of chemotherapy at the same time, so research in this area is of great significance

Method used

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  • Preparation method and application of polycarbonate drug-loaded nano chemosensitizer based on nitric oxide
  • Preparation method and application of polycarbonate drug-loaded nano chemosensitizer based on nitric oxide
  • Preparation method and application of polycarbonate drug-loaded nano chemosensitizer based on nitric oxide

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Embodiment 1, the synthesis of polymer mPEG-PNTC

[0039] Specifically, weigh 0.1g NTC monomer and 0.3g mPEG in a closed reactor in a glove box, add dichloromethane to dissolve, then add 3 drops of bis(bistrimethylsilyl)amine zinc catalyst, and then react Seal the device well, transfer it out of the glove box, and react in an oil bath at 30-50°C for 48 hours, then terminate the reaction with glacial acetic acid, then precipitate in glacial ether, and finally filter and vacuum-dry to obtain the product. NMR results show that its molecular weight is 5000-4800. See attached for NMR characterization figure 1 .

[0040]

Embodiment 2

[0041] Example 2, Preparation of Nitric Oxide Donor Chemosensitizer Containing Mitoxantrone

[0042] Take 0.1mL polymer mPEG-PNTC in DMF solution (10mg / mL) and 10μL mitoxantrone in DMF solution (20mg / mL) and mix well, then slowly add the mixed solution dropwise to the phosphate buffer under ultrasonic conditions , continue to sonicate for 10 min, and then dialyze to remove the organic solvent and uncoated mitoxantrone. The micelles encapsulating mitoxantrone were measured by a microplate reader. Drug loading (DLC) and encapsulation efficiency (DLE) were calculated by the following formulas:

[0043] Drug loading (%) = (loaded drug mass / polymer and drug total mass) × 100%

[0044] Encapsulation efficiency (%)=(loaded drug quality / total drug input amount)×100%

[0045] Table 1 shows the actual encapsulation efficiency of mPEG-PNTC polymer micelles when the theoretical drug loading of mitoxantrone is 5%, 10%, 15% and 20%, respectively.

[0046] Table 1. Characterization of poly...

Embodiment 3

[0049] Example 3, preparation of doxorubicin-loaded micelles by dialysis

[0050] Take 0.1mL of polymer mPEG-PNTC in DMF solution (10mg / mL) and 10μL of doxorubicin in DMF solution (20mg / mL) and mix evenly, then slowly add the mixed solution dropwise to the phosphate buffer under ultrasonic conditions, Continue to sonicate for 10 minutes, and then dialyze to remove the organic solvent and uncoated doxorubicin. The doxorubicin-encapsulated micelles were measured by a microplate reader. Drug loading (DLC) and encapsulation efficiency (DLE) were calculated by the following formulas:

[0051] Drug loading (%) = (loaded drug mass / polymer and drug total mass) × 100%

[0052] Encapsulation efficiency (%)=(loaded drug quality / total drug input amount)×100%

[0053] The dimensions of the samples were measured by a dynamic light scattering analyzer.

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Abstract

The invention discloses a preparation method and application of a polycarbonate drug-loaded nano chemosensitizer based on nitric oxide. The sensitizer is prepared by self-assembling a polycarbonate block copolymer containing a nitric oxide donor and a small molecule chemotherapeutic drug. The polycarbonate drug-loaded nano chemosensitizer based on nitric oxide has the advantages of good water solubility, small toxic and side effects, good stability in a normal physiological environment and the like, and effectively solves the problems of poor water solubility, large toxic and side effects and the like of indissolvable chemotherapeutic drugs such as adriamycin, mitoxantrone and the like in clinical use. The polycarbonate drug-loaded nano chemosensitizer based on nitric oxide also has the features that the drug-loading capacity is high, the tumor targeting property is remarkable, the tumor microenvironment can be regulated and controlled, the ideal chemotherapy sensitization effect is achieved, and tumor recurrence is reduced.

Description

technical field [0001] The invention relates to biomedical polymer materials and pharmaceutical preparations and a preparation method thereof, in particular to the preparation and application of a nitric oxide-based polycarbonate drug-loaded nanometer chemotherapeutic sensitizer. Background technique [0002] Chemotherapy is one of the most widely used methods for clinical treatment of cancer. Its main principle is to use the cytotoxicity of chemotherapeutic drugs to kill tumor cells and inhibit tumor proliferation. However, tumor cells reduce the toxicity of chemotherapy drugs to themselves through multiple mechanisms, such as high levels of glutathione in tumor cells, overexpressed ATP-binding transporters including P-glycoprotein, breast cancer resistance protein and multidrug resistance-related proteins, etc. After chemotherapy drugs enter tumor cells through receptors, they will be detoxified by intracellular glutathione, and the anti-tumor activity of chemotherapy drug...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/785A61K9/14A61K31/136A61K31/555A61K31/704A61K33/243A61P35/00B82Y5/00B82Y40/00C08G64/18C08G64/30
CPCA61K31/785A61K9/14A61K45/06A61K31/704A61K31/136A61K33/243A61K31/555A61P35/00C08G64/183C08G64/30B82Y5/00B82Y40/00A61K2300/00
Inventor 陈维陈家鑫钟伊南赵兵兵黄德春
Owner CHINA PHARM UNIV
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