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Doxorubicin hydrochloride-loaded self-healing hydrogel drug administration system

A doxorubicin hydrochloride, hydrogel technology, applied in the directions of liquid delivery, antineoplastic drugs, drug combination, etc., can solve the problems of dose dependence, application limitation, hair loss and gastrointestinal symptoms, etc., to reduce drug side effects, Good biocompatibility and short preparation cycle

Inactive Publication Date: 2017-08-08
FUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this type of drug is highly toxic, and long-term use can cause dose-dependent irreversible cardiomyopathy, bone marrow suppression, hair loss, and gastrointestinal symptoms. At the same time, the existence of multidrug resistance also limits its clinical application.

Method used

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  • Doxorubicin hydrochloride-loaded self-healing hydrogel drug administration system
  • Doxorubicin hydrochloride-loaded self-healing hydrogel drug administration system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] 1) Dissolve 5.000 g of pullulan in 200 mL of double-distilled water, and stir magnetically to fully dissolve;

[0030] 2) Take 5 mL of 232 mg / mL oxidant potassium periodate solution and add it to the solution obtained in step 1), stir and react for 1.5 h at room temperature and in the dark;

[0031] 3) Add 0.36 mL glycerol to the solution obtained in step 2) and react for 15 min to terminate the oxidation reaction;

[0032] 4) Place the solution obtained in step 3) in a dialysis bag of MWCO 6000, and dialyze at 4°C for 3 days, during which time the water is changed every 6-8 hours;

[0033] 5) Vacuum freeze-dry the dialyzed solution for 3 days to obtain pure solid oxidized pullulan;

[0034] 6) Weigh 1.000 g of the prepared oxidized pullulan, add 20 mL of double distilled water, and dissolve at 37°C;

[0035] 7) Add 40 mg of doxorubicin hydrochloride to the solution obtained in step 6), and fully dissolve at 37 °C;

[0036] 8) Add 250 μL of 0.5 g / mL ε-polylysine aque...

Embodiment 2

[0041] 1) Dissolve 5.000 g of pullulan in 200 mL of double-distilled water, and stir magnetically to fully dissolve;

[0042] 2) Take 5 mL of 232 mg / mL oxidant potassium periodate solution and add it to the solution obtained in step 1), stir and react for 1.5 h at room temperature and in the dark;

[0043] 3) Add 0.36 mL glycerol to the solution obtained in step 2) and react for 15 min to terminate the oxidation reaction;

[0044] 4) Place the solution obtained in step 3) in a dialysis bag of MWCO 6000, and dialyze at 4°C for 3 days, during which time the water is changed every 6-8 hours;

[0045] 5) Vacuum freeze-dry the dialyzed solution for 3 days to obtain pure solid oxidized pullulan;

[0046] 6) Weigh 1.000 g of the prepared oxidized pullulan, add 20 mL of double distilled water, and dissolve at 37°C;

[0047]7) Add 40 mg of doxorubicin hydrochloride to the solution obtained in step 6), and fully dissolve at 37 °C;

[0048] 8) Add 350 μL of 0.5 g / mL ε-polylysine aqueo...

Embodiment 3

[0053] 1) Dissolve 5.000 g of pullulan in 200 mL of double-distilled water, and stir magnetically to fully dissolve;

[0054] 2) Take 5 mL of 232 mg / mL oxidant potassium periodate solution and add it to the solution obtained in step 1), stir and react for 1.5 h at room temperature and in the dark;

[0055] 3) Add 0.36 mL glycerol to the solution obtained in step 2) and react for 15 min to terminate the oxidation reaction;

[0056] 4) Place the solution obtained in step 3) in a dialysis bag of MWCO 6000, and dialyze at 4°C for 3 days, during which time the water is changed every 6-8 hours;

[0057] 5) Vacuum freeze-dry the dialyzed solution for 3 days to obtain pure solid oxidized pullulan;

[0058] 6) Weigh 1.000 g of the prepared oxidized pullulan, add 20 mL of double distilled water, and dissolve at 37°C;

[0059] 7) Add 40 mg of doxorubicin hydrochloride to the solution obtained in step 6), and fully dissolve at 37 °C;

[0060] 8) Add 50 μL of 0.5 g / mL ε-polylysine aqueo...

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Abstract

The invention discloses a doxorubicin hydrochloride-loaded self-healing hydrogel drug administration system and a preparation method thereof. The preparation method comprises the steps of oxidating pullulan into aldehyde-rich oxidated pullulan; by taking the oxidated pullulan, epsilon-polylysine, branched polyethyleneimine and doxorubicin hydrochloride as raw materials, performing Schiff base reaction in a water solution to form a dynamic imine bond cross-linked network, thus obtaining the self-healing hydrogel drug delivery system, wherein the doxorubicin hydrochloride is loaded into the system by two modes of dynamic imine bond cross linking and gel mesh adsorption. The preparation method is simple and easy to operate, the obtained hydrogel drug delivery system has good biocompatibility, biodegradability, temperature and pH sensitivity, self-sealing property and syringeability, and can be directly injected into a diseased region by tumor periphery injection drug administration without surgery implantation, thus greatly alleviating the pain of a patient, slowly releasing the doxorubicin hydrochloride in vivo, being beneficial to reducing of toxic and side effects of a drug, and achieving the aim of efficiently attenuating toxicity in a tumor treatment process.

Description

technical field [0001] The invention belongs to the field of polymer drug carriers, and in particular relates to a self-healing hydrogel drug delivery system loaded with doxorubicin hydrochloride and a preparation method thereof. Background technique [0002] Doxorubicin hydrochloride (Doxorubicin, DOX) is an anthracycline anti-tumor drug commonly used in clinical practice. It enters tumor cells through the cell membrane and acts on DNA to achieve the purpose of anti-tumor. Doxorubicin hydrochloride has a broad anti-tumor spectrum and good curative effect, and is mainly used for the treatment of acute and chronic leukemia, malignant lymphoma and various solid tumors. However, this type of drug is highly toxic, and long-term use can cause dose-dependent irreversible cardiomyopathy, bone marrow suppression, hair loss, and gastrointestinal symptoms. At the same time, the existence of multidrug resistance also limits its clinical application. . In order to solve the above prob...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K31/704A61K47/36A61P35/00C08J3/075C08B37/00A61K9/06
CPCA61K9/0019A61K31/704A61K47/36C08B37/0018C08J3/075C08J2305/00C08J2477/04C08J2479/02
Inventor 程翠张秀丽孟亚彬章志鸿方哲翔张其清
Owner FUZHOU UNIV
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