Preparation and application of nanodiamond drug with high loading and pH-controlled release of doxorubicin

A technology of nano-diamonds and doxorubicin, which is applied in drug combinations, medical preparations of non-active ingredients, anti-tumor drugs, etc., can solve the problems of strong cytotoxicity, killing, lack of specific recognition, etc., and achieve biocompatibility Good sex, stable chemical properties, and the effect of reducing toxic and side effects

Inactive Publication Date: 2018-02-06
SHANXI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these clinically used anticancer drugs usually have strong cytotoxicity and lack of specific recognition. While killing cancer cells, they will also kill normal tissue cells
In addition, chemotherapy also has the disadvantage of low bioavailability of drugs, which is manifested in the low efficiency of drug uptake by cancer cells, and it is difficult for drugs to cross physiological barriers to reach tumor sites during blood circulation.
These problems have limited the dosage and scope of application of anticancer drugs to varying degrees, hindered the application of chemotherapy in cancer treatment, and urgently need people's solution

Method used

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  • Preparation and application of nanodiamond drug with high loading and pH-controlled release of doxorubicin
  • Preparation and application of nanodiamond drug with high loading and pH-controlled release of doxorubicin
  • Preparation and application of nanodiamond drug with high loading and pH-controlled release of doxorubicin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] (1) Preparation of nanodiamond-polyethylene glycol (ND-PEG-COOH) nanoparticles

[0037] Accurately weigh 1.0 mg of carboxylated nano-diamonds, and pass through dimethyl sulfoxide (DMSO), absolute ethanol (C 2 h 5 OH), distilled water (H 2 O) After washing, place in 1.0mL MES (0.1M, pH5.8) buffer solution, ultrasonically disperse for 30min to form a suspension, then add 0.2mg EDC, 0.25mg NHS, stir and react at room temperature for 6h. 15000rpm high-speed centrifugation for 5min, remove the supernatant, and obtain activated carboxyl nano-diamond precipitate;

[0038] Quickly disperse the nano-diamond precipitate with activated carboxyl group into 1.0mL BBS (0.1M, pH8.4) buffer solution, ultrasonically disperse for 10min to form a suspension, then add 0.3mg polyethylene glycol (H 2 N-PEG-COOH), continue to stir and react at room temperature for 12 hours. After the reaction is completed, collect the supernatant by high-speed centrifugation at 15,000 rpm for 5 minutes, an...

Embodiment 2

[0043] (1) The preparation of nano diamond-polyethylene glycol (ND-PEG-COOH) nanoparticles is the same as in Example 1

[0044] (2) Nano diamond-polyethylene glycol-doxorubicin / sodium citrate (ND-PEG-DOX / Na 3 Cit) Preparation of Nanomedicine

[0045] Weigh 1 mg of vacuum-dried nano-diamond-polyethylene glycol (ND-PEG-COOH), add 1 mL of sodium citrate (Na 3 Cit, 1.0M) solution, ultrasonically disperse for 1 hour to form a suspension, then add 0.1 mg doxorubicin (DOX), and react on a shaker in the dark for 6 hours. After the reaction is complete, centrifuge at 15,000 rpm for 5 minutes to collect the supernatant solution, and with 1.0M sodium citrate (Na 3 Cit) continue to wash three times with 15000rpm high-speed centrifugation for 5min to obtain nanodiamond-polyethylene glycol-doxorubicin / sodium citrate (ND-PEG-DOX / Na 3 Cit) nanoparticles, placed in a vacuum oven to preserve for subsequent use. All supernatants were collected into a small beaker and left overnight in a refr...

Embodiment 3

[0047] (1) With embodiment 1 step (1).

[0048] (2) Preparation of nanodiamond-polyethylene glycol-doxorubicin / sodium acetate (ND-PEG-DOX / NaAc) nanomedicine

[0049] Weigh 1 mg of vacuum-dried nano-diamond-polyethylene glycol (ND-PEG-COOH), add 1 mL of sodium acetate (NaAc, 1.0 M) solution, and ultrasonically disperse for 1 hour to form a suspension, then add 0.2 mg of doxorubicin ( DOX), avoid light and react on a shaker for 6 hours. After the reaction is completed, collect the supernatant with 15000rpm high-speed centrifugation for 5min, and continue to wash three times with 1.0M sodium acetate (NaAc) with 15000rpm high-speed centrifugation for 5min to obtain nano-diamond-polymer Ethylene glycol-doxorubicin / sodium citrate (ND-PEG-DOX / NaAc) nano-medicine is stored in a vacuum drying oven for future use. All supernatants were collected into a small beaker and left overnight in a refrigerator at 4°C to determine the mass of DOX adsorbed on ND-PEG-COOH nanoparticles. The absor...

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Abstract

The invention provides the preparation and application of a nano-diamond drug with high load and pH-controlled release of doxorubicin. The present invention first uses H2N-PEG-COOH to modify nano-diamonds, synthesizes ND-PEG-COOH carrier, and then physically adsorbs doxorubicin under the condition of sodium citrate or sodium acetate to obtain the target drug nano-diamond-polyethylene glycol-doxorubicin Sodium citrate (ND‑PEG‑DOX / Na3Cit) or nanodiamond‑polyethylene glycol‑doxorubicin / sodium acetate (ND‑PEG‑DOX / NaAc). Through in vitro drug release experiments, MTT experiments and flow cytometry cell uptake nano-drug experiments, it was shown that ND-PEG-DOX / Na3Cit and ND-PEG-DOX / NaAc can induce tumor cell apoptosis, which can be used in the preparation of anti-tumor drugs in the application.

Description

technical field [0001] The invention relates to a nano-medicine, in particular to a nano-diamond drug with high load and pH-controllable release of doxorubicin, a preparation method thereof, and an application of the drug in preparing antitumor drugs. Background technique [0002] Cancer is a serious threat to human life and health, and its morbidity and mortality are second only to heart disease and infectious diseases worldwide. At present, the main treatment methods for cancer are surgical resection, radiotherapy and chemotherapy. If the tumor grows only in a local area or is detected early, both surgical resection and radiation therapy are suitable for treatment. However, usually when the tumor is discovered, the patient is already in the middle and late stage of the cancer, and it is often accompanied by signs of metastasis and spread of the lesion. In this case, chemotherapy is the only hope for the patient to survive. Traditional chemotherapy is to kill cancer cells...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/60A61K47/69A61K47/04A61P35/00A61K47/52
Inventor 李林李英奇杨斌盛
Owner SHANXI UNIV
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