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Hepatoma targeting carbon nano tube loaded with doxorubicin hydrochloride and preparation method thereof

A technology of doxorubicin hydrochloride and carbon nanotubes, which is applied in the field of medicine, can solve the problems of doxorubicin hydrochloride side effects and limited application, and achieve the effects of small side effects, good effect and simple process route

Inactive Publication Date: 2015-06-10
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Doxorubicin Hydrochloride (DOX), also known as doxorubicin, its mechanism of action is mainly that DOX molecules intercalate into DNA and inhibit the synthesis of nucleic acids. , strong activity and good curative effect, but the serious side effects of doxorubicin hydrochloride greatly limit its application in chemotherapy

Method used

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  • Hepatoma targeting carbon nano tube loaded with doxorubicin hydrochloride and preparation method thereof
  • Hepatoma targeting carbon nano tube loaded with doxorubicin hydrochloride and preparation method thereof
  • Hepatoma targeting carbon nano tube loaded with doxorubicin hydrochloride and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0023] Example 1: Preparation of liver cancer-targeting carbon nanotubes loaded with doxorubicin hydrochloride

[0024] (1) Carboxylation of carbon nanotubes: 200 mg of MWNTs (length 1-2 μm, diameter 10 nm) was added to the H 2 SO 4 / HNO 3 (v:v=3:1) in 100mL of the mixture, sonicate for 5min. Then, the mixture was heated to reflux at 80 °C with magnetic stirring for 4 h. After the oxidation reaction, the mixture was added to 150 mL of ice water and left to stand overnight. The carbon tubes in the mixture were precipitated, and the upper layer of the clear brown transparent liquid was sucked out with a dropper, and the lower layer was filtered with a sand core funnel, and continuously washed with deionized water until neutral. A small amount of deionized water was ultrasonically dissolved and freeze-dried to obtain O-CNTs. TEM showed that the length of carbon nanotubes became shorter and the surface was smoother after acidification. Infrared characterization product with ...

Embodiment 2

[0028] Example 2: In vitro release of liver cancer-targeted carbon nanotubes (O-CNTs-LCH-DOX) loaded with doxorubicin hydrochloride

[0029] Precisely weigh 2 mg of liver cancer-targeting carbon nanotube (O-CNTs-LCH-DOX) freeze-dried powder loaded with doxorubicin hydrochloride of the present invention and disperse them in phosphate buffers of pH 7.4, pH 6.5 and pH 5.5 respectively, Make the concentration 1mg / mL, take 1mL of the sample solution in a dialysis bag with a molecular weight cut-off of 3500, put it into 100mL of the corresponding phosphate buffer, and dialyze it in a constant temperature oscillator at 37°C (frequency 100r / min). Take 1mL at regular intervals and add 1mL of corresponding phosphate buffer at the same time, parallel 3 times. The sample that is taken out is filtered and HPLC is measured doxorubicin hydrochloride content, and the cumulative release curve of 24h is as attached Figure 4 , the in vitro release of liver cancer-targeting carbon nanotubes (O-...

Embodiment 3

[0030] Example 3: In vitro safety evaluation: hemolysis test

[0031] Take 10 mL of fresh rabbit blood and place it in a 200 mL beaker containing glass beads, gently stir with glass beads to remove fibrinogen, and obtain defibrillated blood. Add about 10 times the amount of 0.9% sodium chloride injection, shake well, centrifuge at 1500rpm for 15 minutes, remove the supernatant, and then wash the precipitated red blood cells with sodium chloride injection for 2 to 3 times according to the above method until the supernatant is no longer obvious. until red. Aspirate 3 mL of red blood cells, dilute to 150 mL with 0.9% sodium chloride injection to prepare a 2% red blood cell suspension, and store in a 4°C refrigerator for later use. Take 40 10mL centrifuge tubes and divide them into three groups, which are liver cancer targeting carbon nanotubes (O-CNTs-LCH-DOX) group loaded with doxorubicin hydrochloride, negative control tube (0.9% normal saline nc), positive control tube (dist...

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Abstract

The invention discloses a hepatoma targeting carbon nano tube loaded with doxorubicin hydrochloride and a preparation method thereof. Amidation reaction of amino in a chitosan structure and carboxyl in lactobionic acid is carried out; galactosyl is coupled to chitosan so as to obtain galactosylated chitosan; the galactosylated chitosan is modified onto the carbon nano tube; therefore, the water solubility and the biocompatibility of the carbon nano tube are increased; simultaneously, the specificity of non-reductive galactose or N-acetyl-galactose is identified and taken by utilizing an asialoglycoprotein acceptor on a liver parenchyma cell membrane, so that the active hepatoma targeting effect is realized; simultaneously, doxorubicin hydrochloride is combined with a vector in a non-covalent manner through phi-phi accumulation acting force; and therefore, the hepatoma targeting carbon nano tube loaded with doxorubicin hydrochloride is prepared. The hepatoma targeting carbon nano tube disclosed by the invention is simple in preparation process, moderate in experimental condition and easy to operate; release of the medicine loaded targeting carbon nano tube has pH dependency, good biocompatibility and obvious in-vivo tumour inhibition effect; and thus, the hepatoma targeting carbon nano tube has good practical value.

Description

technical field [0001] The invention relates to a nano drug delivery system that can be used for liver cancer targeting, in particular to a liver cancer targeting carbon nanotube loaded with doxorubicin hydrochloride and a preparation method thereof, belonging to the technical field of medicine. Background technique [0002] Liver cancer is one of the common malignant tumors of the digestive system in my country. Its incidence is second only to gastric cancer and esophageal cancer. It has high malignancy, poor prognosis and high mortality. Surgical resection is the first choice for patients with early liver cancer. However, for patients with advanced liver cancer, non-surgical treatment, especially drug treatment, has become one of the important means of comprehensive treatment. The liver cancer targeted drug delivery system can effectively deliver the drug to the liver lesion, reduce its systemic distribution, reduce the dose and frequency of administration, reduce its adv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K31/704A61P35/00
Inventor 吴正红芮瑶祁小乐陈海燕马宁
Owner CHINA PHARM UNIV
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