Tumor-targeted magnetic hydrogel nanoscale medicine delivery system and construction method and application thereof

A technology of hydrogel nanometer and drug delivery system, which can be used in antitumor drugs, pharmaceutical formulations, drug combinations, etc., can solve the problems of low effective rate of doxorubicin

Inactive Publication Date: 2011-11-02
SOUTH CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Due to the emergence of drug resistance, the effective rate of doxorubicin is less than 20%. At the same time, due to its obvious toxicity to the blood system and gastrointestinal reactions, it can cause nausea, vomiting, hair loss, high fever and other adverse reactions

Method used

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  • Tumor-targeted magnetic hydrogel nanoscale medicine delivery system and construction method and application thereof
  • Tumor-targeted magnetic hydrogel nanoscale medicine delivery system and construction method and application thereof
  • Tumor-targeted magnetic hydrogel nanoscale medicine delivery system and construction method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1 Preparation and characterization of tumor-targeted magnetic nano drug delivery system

[0048] 1.1 Superparamagnetic Fe 3 O 4 Synthesis and surface modification of nanoparticles

[0049] Using chemical co-precipitation method to synthesize Fe3O4 (Fe 3 O 4 )Nanoparticles. Weigh 0.1mol FeSO 4 ·7H 2 O, 0.16mol FeCl 3 ·6H 2 O is placed in a three-necked flask, 140ml ultrapure water is added to it, the three-necked flask is equipped with an electric stirrer, placed in an oil bath, nitrogen protection is introduced, and stirring is carried out at 60℃ for 30min; weigh 0.84mol NaOH and place In a beaker, add 280ml of ultrapure water, stir with a glass rod at 60°C to fully dissolve it. Slowly add the NaOH solution to the iron salt solution (the pH of the mixed solution is 12 at this time), after reacting for 10 minutes, the temperature is raised to 70°C, then HCl solution is added to it to pH=3, and finally 20ml of oleic acid (Oleic acid , OA), after stirring for 3...

Embodiment 2

[0078] Example 2 Fe 3 O 4 -OA / NIPA-AA / TNF-α / IFN- γ / FA / DOX inhibits HepG2 cells in vitro

[0079] 1 Research on the inhibitory effect of drugs on cells

[0080] Digest HepG2 cells with trypsin and collect them, pipette evenly and press 1×10 per well 6 Cells are seeded in 24-well plates. The experiment is divided into four groups: A blank control group (simple cell culture); B free TNF-α(1.5ng / well)+IFN-γ(1.5ng / well)+FA(1.5ng / well)+DOX(20 ng) / well); C free Fe 3 O 4 -OA / NIPA-AA(1.5ng / well)+TNF-α(1.5ng / well)+IFN-γ(1.5ng / well)+FA(1.5ng / well)+DOX(20ng / well); D total Fixed drug group Fe 3 O 4 -OA / NIPA-AA / TNF-α / IFN-γ / FA / DOX (doxorubicin amount is 20ng / well). Under the same conditions (37℃,5%CO 2 ) After culturing for 24 hours, compare the number of cells in the experimental group with respect to the blank group by cell counting, and calculate the cell survival rate.

[0081] Study on the inhibitory effect of different doses of nano-medicine on cells

[0082] The inhibitory effe...

Embodiment 3

[0083] Example 3 Fe 3 O 4 -OA / NIPA-AA / TNF-α / IFN-γ / FA inhibits HepG2 cells in vivo

[0084] 1 Cultivation of liver cancer cells (HepG2 cell line)

[0085] Use DMEM medium (containing 10% newborn calf serum, 0.03mg / ml penicillin, 0.05mg / ml streptomycin, pH=7.2~7.4), at 37℃, 5%CO 2 Subculture in an incubator.

[0086] Establishment of animal model of liver cancer

[0087] For animal experiments, four-week-old BALB / c-nu / nu nude mice (nude mice) were selected. A total of 20 were purchased, all male, weighing 14.5±3.2g, and they were all purchased from the Production Department of Guangdong Medical Experimental Animal Center, SPF grade. License number: SCXK (Guangdong) 2008-0002; the batch of nude mice is 0079266. After purchasing the nude mice, they will be raised in the SPF nude mouse room of the Animal Experiment Center of Sun Yat-sen University North Campus (license number SYXK (Guangdong) 2007-0081). Twenty nude mice were randomly divided into 5 groups, 4 in each group, numb...

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Abstract

The invention discloses a tumor-targeted magnetic hydrogel nanoscale medicine delivery system, a construction method and application thereof. The tumor-targeted magnetic hydrogel nanoscale medicine delivery system is prepared by the following steps of: grafting a hydrogel with temperature and pH sensitivity onto the surfaces of ferroferric oxide nanoparticles to form a magnetic hydrogel carrier by a photochemical immobilization method, grafting tumor necrosis factor-alpha, interferon-gamma and a targeted molecular ligand, namely folic acid on the surface of the magnetic hydrogel carrier, and absorbing adriamycin. The system can deliver an antitumor medicine to the periphery of tumor cells by utilizing active targeting, the tumor necrosis factor-alpha, the interferon-gamma and a tumor cellsurface receptor are combined and used for inducing the programmed death of the tumor cells, and the antitumor medicine, namely the adriamycin enters the cells along with the carrier and then is released. Through the experiment, the medicine delivery system has a negligible toxic or side effect, and efficiently inhibits the growth of cancer cells through the coaction mechanism of the tumor necrosis factor-alpha, the interferon-gamma and the antitumor medicine, namely the adriamycin inside and outside the tumor cells.

Description

technical field [0001] The invention relates to the technical field of preparation of anticancer drugs, in particular to a tumor-targeting magnetic hydrogel nano drug delivery system and its construction method and application. Background technique [0002] According to a research report released by the International Cancer Research Center of the World Health Organization in April 2011, according to the current trend of cancer incidence, the incidence of cancer worldwide will increase by 50% in 2020, and the number of new cancer patients worldwide will reach 15 million people. Among these many types of cancers, liver cancer is one of the most common malignant tumors, which has the characteristics of high incidence, short course of disease, high degree of malignancy, and poor prognosis. Western medicine surgery, radiotherapy and chemotherapy, combined with traditional Chinese medicine are generally used clinically, but there are problems such as large toxic and side effect...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K47/32A61K47/02A61K47/22A61K47/48A61K38/21A61K38/19A61K31/704A61P35/00
Inventor 刘俊明关燕清黄峥
Owner SOUTH CHINA NORMAL UNIVERSITY
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