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Human recombinant epidermal growth factor (hrEGF)-modified cisplatin-loaded polymeric nanoparticles and preparation method and application thereof

A polymer nanoparticle and nanoparticle technology, applied in the field of biomedical technology and nanomedicine, can solve the problems of limited dose, bone marrow suppression, and decreased quality of life, and achieve the effects of good biocompatibility and good degradability.

Inactive Publication Date: 2012-11-28
RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the lack of selectivity and toxicity of chemotherapy drugs, it often kills normal cells as well as tumor cells, leading to myelosuppression, renal insufficiency, gastrointestinal reactions, cardiac conduction disorders and other conditions in patients. The quality deteriorated severely, and some patients even died due to complications such as infection and bleeding caused by chemotherapy
As a result, the availability of the drug is limited and the dosage is limited
In addition, there are some elderly and weak patients or patients with heart, liver and kidney insufficiency who cannot tolerate the toxicity of chemotherapy and cannot undergo chemotherapy, resulting in rapid progression of ovarian cancer and death

Method used

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  • Human recombinant epidermal growth factor (hrEGF)-modified cisplatin-loaded polymeric nanoparticles and preparation method and application thereof
  • Human recombinant epidermal growth factor (hrEGF)-modified cisplatin-loaded polymeric nanoparticles and preparation method and application thereof
  • Human recombinant epidermal growth factor (hrEGF)-modified cisplatin-loaded polymeric nanoparticles and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037]Example 1: Preparation of hrEGF-modified cisplatin-loaded polymer nanoparticles

[0038] 1) Accurately weigh 4 mg of mPEG-PLGA-PLL, add it into 200 μl of dichloromethane-methanol (3:2) and dissolve to form the organic phase. Take 20 μl of cisplatin solution with a concentration of 10 mg / ml as the water phase, and the cisplatin solution is water-dimethylsulfoxide (3:2). Add cisplatin solution into the organic phase, 350w, 1min ultrasonic emulsification to form colostrum evenly. Weigh 1g of F68 and add it into 100ml of ultrapure water to fully dissolve it to a concentration of 1%, forming the external aqueous phase. The volume ratio of the inner water phase to the outer water phase is 1:8. .The prepared colostrum was immediately added to the external water phase, 350w, 1min, ultrasonic emulsification again, and then vacuum rotary evaporation for 5-8min, so that the organic solvent was completely evaporated, and the colloidal solution of cisplatin-loaded mPEG-PLGA-PLL nan...

Embodiment 2

[0040] Example 2: In vitro sustained-release experiment of polymer nanoparticles loaded with cisplatin

[0041] Take a certain amount of cisplatin-loaded nanoparticles into a pre-treated dialysis bag (MWCO, 3500), place it in a conical flask filled with 18ml of PBS (PH=7.4), and dialyze at a constant temperature of 37°C and 120r / min. Take out 2ml of the dialysate at predetermined time intervals, supplement 2ml of PBS solution at 37°C at the same time, and measure the platinum content in the dialysate with an inductively coupled plasma emission spectrometer. Calculate the cumulative drug release at different times, and draw the drug release curve in vitro. Such as Figure 6 . .

Embodiment 3

[0042] Example 3: Culture of Ovarian Cancer Cell Lines

[0043] The human ovarian cancer cell line SKOV3 is naturally resistant to various drugs such as cisplatin. Routinely culture SKOV3 cells with 10% FCS DMEM medium containing 1% (v / v) penicillin-streptomycin (100U / ml penicillin G and 100ug / ml streptomycin), in a 37°C incubator (95% o 2 ,5%CO 2 ) incubation, and the cells in the logarithmic growth phase were taken for experiments.

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Abstract

The invention relates to the technical field of medicines, in particular to human recombinant epidermal growth factor (hrEGF)-modified cisplatin-loaded polymeric nanoparticles and a preparation method and application thereof. The hrEGF-modified cisplatin-loaded methoxy polyethylene glycol-polylactic-co-glycolic acid-polylysine (mPEG-PLGA-PLL) nanoparticles are obtained by preparing cisplatin-loaded nanoparticles by taking mPEG-PLGA-PLL as a carrier by an ultrasonic emulsification / solvent evaporation method, and then connecting an amino-terminated group and a hrEGF. The nanoparticles can be specifically combined with epidermal growth factor receptors (EGFR) of the surfaces of tumor cells, and the endocytosis is performed, so that the toxic or side effect of cisplatin is reduced, and the aims of reducing poisonousness and synergizing are fulfilled. The nanoparticles can be used for the preparation of anti-tumor medicines; and particularly, the treatment research of ovarian cancer proves that the nanoparticles have high targeting, have a strong killing effect, and have a good application prospect in the chemotherapy of ovarian cancer.

Description

technical field [0001] The invention relates to medicines in the fields of biomedicine technology and nano medicine and a preparation method thereof, in particular to a cisplatin-loaded polymer nanoparticle modified with active targeting hrEGF, its preparation and its application. Background technique [0002] Ovarian cancer is the most malignant disease among gynecological tumors, and ranks first in the mortality rate of gynecological malignant tumors, seriously threatening women's reproductive health. The onset of ovarian cancer is occult, and it is very prone to invasion and distant metastasis. About 70% to 80% of ovarian cancer patients are diagnosed as stage III / IV, and their five-year survival rate is only about 30%. The treatment of ovarian cancer is mainly based on complete tumor reduction surgery. However, because the metastases are mostly scattered and widely planted in the abdominal cavity, it is still impossible to completely remove the tumor by surgery. chemoth...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K47/42A61K31/282A61P35/00A61K47/34
Inventor 狄文段友容王云飞刘培峰
Owner RENJI HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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