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Preparation method of hyaluronic acid targeted carbon nano-tube loaded anti-cancer medicine

A technology of hyaluronic acid and carbon nanotubes, applied in the direction of antineoplastic drugs, drug combinations, and pharmaceutical formulations, to achieve high drug loading capacity, mild experimental conditions, and simple preparation methods

Inactive Publication Date: 2014-07-02
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] A search of domestic and foreign literature and patents on DOX targeted transport shows that: carbon nanotubes modified with hyaluronic acid are used as carrier materials to load doxorubicin through π-π stacking to achieve multiple functions of targeted and pH-sensitive release. research not yet reported

Method used

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  • Preparation method of hyaluronic acid targeted carbon nano-tube loaded anti-cancer medicine
  • Preparation method of hyaluronic acid targeted carbon nano-tube loaded anti-cancer medicine
  • Preparation method of hyaluronic acid targeted carbon nano-tube loaded anti-cancer medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] (1) The carboxylated CNT (344.9mg) was dissolved in 40mL DMSO, and then EDC (354.32mg) was added to activate the reaction with stirring for 3h. Under stirring, 10 mL of DMSO solution containing PEI (540.01 mg) was added dropwise, and the reaction was stirred for 24 hours under ultrasonic stirring at room temperature. Finally, put the reaction solution into a dialysis bag (MW=100,000), and remove unreacted impurities and by-products by dialysis. Firstly, dialyze with PBS buffer for 2 times, 2L each time, and then dialyzed with distilled water 7 times. Finally, the product was freeze-dried to obtain MWCNT / PEI.

[0053] (2) Weigh 360mg MWCNT / PEI in water and add 12.5mg FITC in DMSO solution. Weigh 1.8g hyaluronic acid in water and add 120.96mg EDC to activate for three hours, then add to MWCNT / PEI solution, stir and react for 24h. Finally, put the reaction solution into a dialysis bag (MW=100,000), and remove unreacted impurities and by-products by dialysis. Firstly, dialyze...

Embodiment 2

[0056] (1) Dissolve carboxylated CNT (300mg) in 30mL DMSO, and then add EDC (304mg) to activate the reaction with stirring for 3h. Under stirring, 10 mL of DMSO solution containing PEI (452.3 mg) was added dropwise, and the reaction was stirred at room temperature with ultrasonic for 24 hours. Finally, put the reaction solution into a dialysis bag (MW=100,000), and remove unreacted impurities and by-products by dialysis. Firstly, dialyze with PBS buffer for 2 times, 2L each time, and then dialyzed with distilled water 7 times. Finally, the product was freeze-dried to obtain MWCNT / PEI.

[0057] (2) Weigh 200 mg of MWCNT / PEI in water and add 12.5 mg of FITC in DMSO solution. Weigh 1 g of hyaluronic acid in water and add 70 mg of EDC to activate it for three hours, then add it to the MWCNT / PEI solution and stir for 24 hours. Finally, put the reaction solution into a dialysis bag (MW=100,000), and remove unreacted impurities and by-products by dialysis. Firstly, dialyze with PBS buf...

Embodiment 3

[0060] (1) Dissolve 10 mg of MWCNT / PEI-FI-HA in 10 mL of water, add 4 mL of DOX (4 mg) aqueous solution dropwise with stirring, adjust the pH value = 8.5 with sodium hydroxide, at room temperature , Stir for 4h. Finally, put the solution into a dialysis bag (MW=8,000~14,000), and remove the connected drug by dialysis. Firstly, it is dialyzed with PBS buffer 3 times, 2L each time. Finally, the product was freeze-dried to obtain the CNT / DOX drug-loaded composite.

[0061] (2) The above-mentioned MWCNT / PEI-FI-HA / DOX drug-carrying complex was slowly released at 37°C and two different pH buffers (pH=5.8, pH=7.4), and the release was detected by UV-Vis To study its release effect on DOX.

[0062] (3) The above-mentioned MWCNT / PEI-FI-HA / DOX drug-carrying complex and the pure drug DOX and MWCNT / PEI-FI-HA at the same concentration were respectively applied to human cervical cancer cells (HeLa cells). After 24 hours of culture To study the toxicity of MWCNT / PEI-FI-HA / DOX drug-loaded compl...

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Abstract

The invention relates to a preparation method of a hyaluronic acid targeted carbon nano-tube loaded anti-cancer medicine. The preparation method disclosed by the invention comprises the following steps: (1), chemically bonding a multi-walled carbon nano-tube (MWCNT) with PEI (Polyetherimide) in dimethyl sulfoxide through EDC (Ethylene Dichloride), dialyzing, freeze-drying, and synthesizing MWCNT / PEI; (2), dissolving hyaluronic acid in water, and activating by adding EDC; (3), adding FITC (Fluorescein Isothiocyanate) into MWCNT / PEI to stir, adding activated hyaluronic acid (HA), dialyzing, freeze-drying, and synthesizing MWCNT / PEI-FI-HA; and (4), dissolving the MWCNT / PEI-FI-HA in water, adding an aqueous solution of DOX (Doxycycline), adjusting the pH value, sufficiently stirring, dialyzing, and freeze-drying, thus obtaining a medicine loading compound. The preparation method disclosed by the invention is simple in process and easy to operate; the experiment is carried out at normal temperature and normal pressure; after being loaded with the DOX, the hyaluronic acid targeted carbon nano-tube loaded anti-cancer medicine prepared by the preparation method disclosed by the invention has the effects of releasing and actively locating cells in a pH sensitive manner, and therefore, the preparation method disclosed by the invention has a good practical value.

Description

Technical field [0001] The invention belongs to the field of loading anticancer drugs, and particularly relates to a preparation method of hyaluronic acid targeted carbon nanotubes loading anticancer drugs. Background technique [0002] The side effects and poor water solubility of anti-cancer drugs have always been bottlenecks in tumor chemotherapy, so the use of drug delivery systems has received extensive attention. With its unique size range (1-100nm), the nano drug delivery system can not only reduce the biological toxicity of the drug, and effectively improve the solubility and stability of the drug, but also can and can pass the modification of the drug carrier, the selection of the carrier drug and the loading method Designed to control the sustained release and directional delivery of drugs, so as to achieve the best therapeutic effect. [0003] As a new type of nano-level material, carbon nanotubes have shown good potential in biological applications. Because carbon nano...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K31/704A61P35/00
Inventor 史向阳曹雪雁陶磊
Owner DONGHUA UNIV
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