Preparation method and application of a thiolated polysaccharide-based hydrogel capable of in-situ injection molding and its drug carrier

Abstract

The invention belongs to the field of tissue engineering scaffolds, and discloses a preparation method and application of a thiolated polysaccharide-based hydrogel capable of in-situ injection molding and a drug carrier thereof. The thiolated polysaccharide-based hydrogel is composed of 3% to 6% (w / v) thiolated polysaccharide and 10%-29% (w / v) sodium β-glycerophosphate form a thiolated polysaccharide-based hydrogel that can be molded in situ, in which the thiolated polysaccharide can be coated One or more of drug-loaded liposomes, drug-loaded thiol halloysite or polypeptides form a thiol-polysaccharide-based hydrogel drug carrier that can be molded in situ. The mercapto-polysaccharide-based hydrogel capable of in-situ injection molding and its drug carrier can realize gelation under human physiological temperature conditions, and have temperature sensitivity, injectability and water absorption.

Description

technical field

[0001] The invention belongs to the field of tissue engineering, and in particular relates to a preparation method and application of a thiolated polysaccharide-based hydrogel capable of in-situ injection molding and a drug carrier thereof. Background technique

[0002] The skin is an important part of the human body. It is in direct contact with the outside world and is vulnerable to various traumas, such as burns, scratches, infections, tumor resections, and skin ulcers caused by diabetes. The resection and recurrence of bone tumors will increase the pain of the patient in the second operation. Anti-tumor drugs can be entrapped in the gel, which can fill the defect and prevent tumor recurrence. The release of the drug can be controlled by the entrapment of the drug, and the side effects of the tumor drug can be reduced. It has a certain application prospect.

[0003] Natural polysaccharide materials such as sodium alginate, hyaluronic acid, chitosan and ot...

Examples

Embodiment 1

[0053] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiethylene Amine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0054] (2) Add cysteine ​​(the molar ratio of chitosan:cysteine ​​is 3:1) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the system PH=5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain the thiolated chitosan (CSSH) sample, which was preserved at 4°C;

[0055] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator at -20°C...

Embodiment 2

[0058] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-dicarbonate Imine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0059] (2) Add cysteine ​​(the molar ratio of chitosan: cysteine ​​is 1:1) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the system PH=5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain the thiolated chitosan (CSSH) sample, which was preserved at 4°C;

[0060] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator at -20°C fo...

Embodiment 3

[0063] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-dicarbonate Imine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0064] (2) Add cysteine ​​(the molar ratio of chitosan: cysteine ​​is 1:3) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the pH of the system to 5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain a thiolated chitosan (CSSH) sample, which was stored at 4°C;

[0065] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator at -20...

technical field

[0001] The invention belongs to the field of tissue engineering, and in particular relates to a preparation method and application of a thiolated polysaccharide-based hydrogel capable of in-situ injection molding and a drug carrier thereof. Background technique

[0002] The skin is an important part of the human body. It is in direct contact with the outside world and is vulnerable to various traumas, such as burns, scratches, infections, tumor resections, and skin ulcers caused by diabetes. The resection and recurrence of bone tumors will increase the pain of the patient in the second operation. Anti-tumor drugs can be entrapped in the gel, which can fill the defect and prevent tumor recurrence. The release of the drug can be controlled by the entrapment of the drug, and the side effects of the tumor drug can be reduced. It has a certain application prospect.

[0003] Natural polysaccharide materials such as sodium alginate, hyaluronic acid, chitosan and ot...

Examples

Embodiment 1

[0053] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiethylene Amine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0054] (2) Add cysteine ​​(the molar ratio of chitosan:cysteine ​​is 3:1) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the system PH=5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain the thiolated chitosan (CSSH) sample, which was preserved at 4°C;

[0055] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator at -20°C...

Embodiment 2

[0058] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-dicarbonate Imine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0059] (2) Add cysteine ​​(the molar ratio of chitosan: cysteine ​​is 1:1) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the system PH=5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain the thiolated chitosan (CSSH) sample, which was preserved at 4°C;

[0060] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator at -20°C fo...

Embodiment 3

[0063] (1) Weigh 1g of chitosan and dissolve it in 100mL of 0.5% (v / v) acetic acid aqueous solution, add 0.9586g of 1-ethyl-3-(3-dimethylaminopropyl)-dicarbonate Imine hydrochloride (EDAC) and 0.5754g of N-hydroxysuccinimide (NHS), stirred at room temperature for 15 minutes in the dark;

[0064] (2) Add cysteine ​​(the molar ratio of chitosan: cysteine ​​is 1:3) to the reaction system of step (1), add 1mol / L NaOH solution to adjust the pH of the system to 5, room temperature, dark Stir the reaction for 5 hours; sequentially use HCl solution with pH=5.0, HCl solution with pH=5.0 containing 1% (w / v) NaCl and HCl solution with pH=5.0 as the dialysate, each in the dark for 1 day, and dialyze for 3 days in total. day, and finally freeze-dried to obtain a thiolated chitosan (CSSH) sample, which was stored at 4°C;

[0065] (3) Add the thiolated chitosan prepared in step (2) into deionized water with pH = 8, fully dissolve it under magnetic stirring, put it into a refrigerator at -20...

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