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A kind of ph-sensitive type loaded doxorubicin hydrochloride silver nanocluster hydrogel and application thereof

A technology of doxorubicin hydrochloride and silver nanoclusters is applied in the directions of non-active ingredients medical preparations, medical preparations containing active ingredients, organic active ingredients, etc., which can solve the problem of low encapsulation efficiency and limited doxorubicin preparation The application of doxorubicin preparations, the increase of toxic and side effects, etc., can improve the tumor inhibition rate, maintain the effective concentration, and achieve the effect of good sustained release function.

Active Publication Date: 2018-08-28
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, in the synthesis process of doxorubicin preparations, various organic reagents are often added, such as cross-linking agents, reducing agents and protective agents, which may increase new toxic and side effects
At the same time, due to factors such as complex process and harsh production conditions, the encapsulation rate of doxorubicin preparations is not high, and it is easy to leak, which limits the clinical application of doxorubicin preparations.

Method used

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  • A kind of ph-sensitive type loaded doxorubicin hydrochloride silver nanocluster hydrogel and application thereof
  • A kind of ph-sensitive type loaded doxorubicin hydrochloride silver nanocluster hydrogel and application thereof
  • A kind of ph-sensitive type loaded doxorubicin hydrochloride silver nanocluster hydrogel and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] (1) Prepare 0.01mol / L AgNO 3 Solution, take 5mL and place it in a microwave reactor, the stirring speed is 300r / min, the heating power is 100W, and 10mL, 0.05mol / L cysteine ​​solution is added dropwise, and reacted for 0.5h to prepare the silver nanocluster dispersion.

[0024] (2) Add 0.5mL citric acid solution with a concentration of 0.01mol / L to 5mL silver nanocluster dispersion, place it on a small shaker, shake at a speed of 2.5r / min, and irradiate with 200nm ultraviolet light at a power of 15W. The time is 1h. When the solution is transparent, add 0.5mL NaHCO with a concentration of 0.05mol / L 3 After adjusting the pH of the solution to 4, centrifuge at a high speed of 6000r / min for 5min, add 0.2mg of doxorubicin hydrochloride powder, place it in a high-pressure reaction kettle, feed nitrogen, adjust the temperature in the kettle to 20°C, and the pressure in the kettle to be 8 MPa, reacted for 10 minutes to obtain a red clear jelly, which is pH-sensitive doxorubi...

Embodiment 2

[0027] (1) Prepare 0.01mol / L AgNO 3 Solution, take 5mL and place it in a microwave reactor with a stirring speed of 500r / min and a heating power of 150W, and add 15mL of a 0.05mol / L cysteine ​​solution dropwise, and react for 1h to prepare a silver nanocluster dispersion.

[0028] (2) Add 1 mL of citric acid solution with a concentration of 0.05 mol / L to 10 mL of silver nanocluster dispersion, place it on a small shaker, shake at a speed of 25 r / min, and irradiate with 200 nm ultraviolet light with a power of 15 W and an irradiation time of 1.5h. When the solution is transparent, add 2 mL of 0.05 mol / L NaHCO 3 After adjusting the pH of the solution to 5, centrifuge at a high speed of 8000r / min for 10min, add 1mg of doxorubicin hydrochloride powder, put it in a high-pressure reaction kettle, feed nitrogen, adjust the temperature in the kettle to 20°C, and the pressure in the kettle to 10MPa , and reacted for 20 minutes to obtain a red clear jelly, which is a pH-sensitive doxo...

Embodiment 3

[0030] (1) Prepare 0.02mol / L AgNO 3 Solution, take 5mL and put it in a microwave reactor, the stirring speed is 1000r / min, the heating power is 200W, and 50mL, 0.01mol / L cysteine ​​solution is added dropwise, and the reaction is 1.5h to prepare the silver nanocluster dispersion.

[0031] (2) Add 2 mL of citric acid solution with a concentration of 0.1 mol / L to 50 mL of silver nanocluster dispersion, place it on a small shaker, shake at a speed of 50 r / min, and irradiate with 250 nm ultraviolet light at a power of 40 W for a duration of 2h. When the solution is transparent, add 5 mL of 0.05 mol / L NaHCO 3 After adjusting the pH of the solution to 6, centrifuge at a high speed of 11000r / min for 30min, add 10mg of doxorubicin hydrochloride powder, put it in a high-pressure reaction kettle, feed nitrogen, adjust the temperature in the kettle to 25°C, and the pressure in the kettle to 20MPa , and reacted for 30 minutes to obtain a red clear jelly, which is a pH-sensitive doxorubic...

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Abstract

The invention provides pH-sensitive doxorubicin hydrochloride loaded silver nano-cluster hydrogel. A preparation method of the silver nano-cluster hydrogel comprises the following steps: (1), an AgNO3 solution is prepared, placed in a microwave reactor, stirred and heated, a cysteine solution is added dropwise, and a silver nano-cluster dispersing agent is prepared through reaction; (2), a citric acid solution is added to the silver nano-cluster dispersing agent, the mixture is placed on a small shaking table and subjected to ultraviolet irradiation, an NaHCO3 solution is added to regulate pH after the solution is transparent, high-speed centrifugation is performed, doxorubicin hydrochloride powder is added, the mixture is placed in a high-pressure reactor, nitrogen is introduced, the pressure and the temperature in the reactor are adjusted, red and clear jelly, namely, the pH-sensitive doxorubicin hydrochloride loaded silver nano-cluster hydrogel, is obtained through reaction. The silver nano-cluster hydrogel is taken as a carrier to coat doxorubicin hydrochloride and is injected to a tumor position through orthotopic injection, the pH of the tumor position is responded, so that slow drug release is realized, the tumor inhibition rate is increased, and cardiac toxicity is reduced.

Description

technical field [0001] The invention relates to the technical field of nano-cluster hydrogel, in particular to a drug-loaded hydrogel sensitive to pH, a preparation method and application thereof. Background technique [0002] Doxorubicin (DOX) is an anthracycline antitumor drug, which can inhibit the synthesis of RNA and DNA, and has a wide antitumor spectrum. It has certain treatments for breast cancer, gastric cancer, liver cancer, ovarian cancer, lung cancer and other cancers. Effect. Doxorubicin hydrochloride is its salt preparation, orange-red loose block or powder, easily soluble in water. The toxic and side effects of doxorubicin, such as cardiotoxicity, inhibition of bone marrow hematopoietic function, and renal toxicity, inhibit the further application of doxorubicin. In order to ensure the therapeutic effect of doxorubicin and reduce the side effects, many studies have focused on the development of doxorubicin preparations, including liposomes, magnetic nanopart...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/06A61K31/704A61K47/20A61K47/02A61P35/00
Inventor 沈晓芳庞月红石璐马芸
Owner JIANGNAN UNIV
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