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Mesoporous silicon dioxide-methotrexate-mitoxantrone nanoparticles as well as preparation, activity and application thereof

A technology of mesoporous silica and methotrexate, applied in mesoporous silica-methotrexate/mitoxantrone nanoparticles, MSNN-MTX/MIT can solve the problem in the field of preparing MTX and MIT There is no problem of improving the survival period, cure rate and toxicity of cancer patients

Inactive Publication Date: 2018-02-13
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, similar to the combination of conventional MTX and MIT, the above-mentioned combination chemotherapy regimen still does not improve the survival time, cure rate and toxicity of cancer patients

Method used

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  • Mesoporous silicon dioxide-methotrexate-mitoxantrone nanoparticles as well as preparation, activity and application thereof
  • Mesoporous silicon dioxide-methotrexate-mitoxantrone nanoparticles as well as preparation, activity and application thereof
  • Mesoporous silicon dioxide-methotrexate-mitoxantrone nanoparticles as well as preparation, activity and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Example 1 Preparation of MSNN-MTX / MIT

[0018] 1) Preparation of MSNN

[0019] Dissolve 1 g of cetyltrimethylammonium bromide in 480 mL of distilled water, add 3.5 mL of aqueous sodium hydroxide solution (2M) with stirring, heat at 80°C for 1 h, and stir vigorously until the solution becomes clear. Then, 5 mL of tetraethyl orthosilicate and 1 mL of 3-aminopropyltrimethoxysilane were added rapidly, and heated at 80° C. for 2 h. The reaction mixture was cooled, filtered, and the filter cake was washed three times with 20 mL of distilled water and three times with 20 mL of ethanol, and dried under vacuum at 70°C for 24 hours. The dried solid was refluxed in a mixed solvent of 350mL methanol and 7mL concentrated hydrochloric acid for 24h. The reaction mixture was cooled, filtered, and the filter cake was washed three times with 20 mL of distilled water and three times with 20 mL of ethanol, and dried under vacuum at 70°C for 24 hours. 1.2 g of amino-functionalized mesopo...

Embodiment 2

[0025] Example 2 Determination of the nanostructure of MSNN-MTX / MIT

[0026] 1) Determination of scanning electron microscope Weigh 1 mg of MSNN, MSNN-MTX and MSNN-MTX / MIT respectively, disperse it with 1.5 mL of absolute ethanol ultrasonically, take 100 μL and drop it on the surface of a glass slide, dry it at 37°C for 3 days, and place it on a scanning electron microscope (JSM -6360LV, JEOL, Japan) to observe its shape, see the results Figure 5 .

[0027] 2) Determination by transmission electron microscope Weigh 1 mg of MSNN, MSNN-MTX and MSNN-MTX / MIT respectively, disperse them with 1.5 mL of absolute ethanol ultrasonically, take about 10 μL and drop them on the surface of the copper grid of the transmission electron microscope, dry them at 37°C for 3 days, and put them on the surface of the transmission electron microscope. (JEM-1230, JEOL, Japan) to observe its morphology, see the results Figure 5 .

[0028] 3) Determination of Zeta Potential Weigh 1 mg MSNN, MSNN-M...

Embodiment 3

[0029] Embodiment 3 evaluates the antitumor activity of MSNN-MTX / MIT, mouse survival period and toxicity

[0030] For male ICR mice (weight 20±2g, purchased from Beijing Weitong Lihua Animal Experiment Technology Co., Ltd.), the S180 tumor fluid was diluted to 1.5×10 7 Each mouse was inoculated with 0.2 mL of tumor fluid in the right armpit, and the tumor volume was measured with a vernier caliper every day to observe the tumor growth. The tumor volume grows to 1.0cm within 7 days after inoculation of tumor fluid 3 At , all mice were weighed and randomly divided into 3 groups, 12 mice in each group, receiving CMC-Na treatment, MTX+MIT treatment and MSNN-MTX / MIT treatment respectively. Pass MSNN-MTX / MIT through a 200-mesh sieve, use physiological saline containing 5‰ CMC-Na as a vehicle, and administer it by intraperitoneal injection. The dosage of CMC-Na group was 0.2mL per mouse, the dosage of MTX+MIT group was 4mg / kg MTX and 0.5mg / kg MIT, and the dosage of MSNN-MTX / MIT gro...

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Abstract

The invention discloses nano-scale mesoporous silicon dioxide-methotrexate-mitoxantrone nanoparticles. Its preparation method is disclosed, that is, amino functionalized mesoporous silica nanoparticles (MSNN) are prepared by modifying amino groups on the surface of mesoporous silica nanoparticles, and then the amino groups of MSNN are covalently combined with MTX to form methotrexate ‑Amino-modified mesoporous silica nanoparticles (MSNN‑MTX), and finally load mitoxantrone into the nanopores of MSNN‑MTX to obtain nanoscale mesoporous silica‑methotrexate / mitoxantrone Quinone nanoparticles (MSNN‑MTX / MIT). Its antitumor effect is disclosed. Compared with the combined application of conventional MTX and MIT, MSNN‑MTX / MIT significantly prolongs the survival time of S180 mice, improves the curative effect and reduces systemic toxicity. Therefore, the present invention discloses the application of MSNN-MTX / MIT in the preparation of antitumor drugs combined with MTX and MIT. The MSNN-MTX / MIT of the present invention has a good clinical application prospect.

Description

field of invention [0001] The invention relates to a mesoporous silicon dioxide-methotrexate (MTX) / mitoxantrone (MIT) nanoparticle (MSNN-MTX / MIT). Its preparation method involves modifying amino groups on the surface of mesoporous silica nanoparticles to prepare amino-functionalized mesoporous silica nanoparticles (MSNN), and then the amino groups of MSNN are covalently combined with MTX to form methotrexate- Amino-modified mesoporous silica nanoparticles (MSNN-MTX), and finally load mitoxantrone into the nanopores of MSNN-MTX to obtain nanoscale mesoporous silica-methotrexate / mitoxantrone Nanoparticles (MSNN-MTX / MIT). Involved in its antitumor effect. Compared with the combined application of conventional MTX and MIT, MSNN-MTX / MIT significantly prolongs the survival time of S180 mice, improves the curative effect and reduces systemic toxicity. Therefore, the present invention discloses the application of MSNN-MTX / MIT in the preparation of antitumor drugs combined with MTX ...

Claims

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Application Information

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IPC IPC(8): A61K47/52A61K47/69A61K31/519A61K9/14A61K47/04A61P35/00A61K31/136
CPCA61K31/519A61K31/136A61K2300/00
Inventor 彭师奇赵明王玉记宋宁
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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