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Microenvironment-sensitive drug-loading nano capsules with tumor cell biological reducibility and preparation method thereof

A drug-loaded nano- and tumor cell technology, applied in the field of biomedical materials, can solve the problems of normal tissue side effects, low safety, and poor biocompatibility of loaded nanocapsules

Inactive Publication Date: 2017-08-29
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Aiming at the above-mentioned deficiencies in the prior art, the present invention provides a drug-loaded nanocapsule sensitive to the bioreductive microenvironment of tumor cells and a preparation method thereof, which can effectively solve the problem of poor biocompatibility of the existing drug-loaded nanocapsules. Normal tissue has toxic side effects, low safety and other issues

Method used

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  • Microenvironment-sensitive drug-loading nano capsules with tumor cell biological reducibility and preparation method thereof
  • Microenvironment-sensitive drug-loading nano capsules with tumor cell biological reducibility and preparation method thereof
  • Microenvironment-sensitive drug-loading nano capsules with tumor cell biological reducibility and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] The preparation of the hyaluronic acid (HA-Cys) that embodiment 1 cystamine binds

[0052] Dissolve 5g of hyaluronic acid in 250ml of PBS (0.01mol / L, pH=7.4), add 3 equivalents of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and 3 equivalents 1-Hydroxybenzotriazole, stirred at room temperature, activated carboxyl group for 4 hours; then added 3 times equivalent of cystamine dihydrochloride, stirred and reacted at room temperature for 24 hours, and then dialyzed with deionized water for 72 hours (the molecular weight cut-off of the dialysis bag was 3500 channels Dayton), to remove unreacted molecules and condensing agents, etc.; among them, hyaluronic acid, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole and cystamine The molar ratio of dihydrochloride is 1:3:3:3.

Embodiment 2

[0053] Example 2 Preparation of hyaluronic acid (GM-HA-SH) combined with esterified cystamine

[0054] Dissolve 1 g of cystamine-conjugated hyaluronic acid (HA-Cys) in 25 ml of PBS / dimethylformamide mixture (the volume ratio of PBS and dimethylformamide is 4:1), and add excess methacrylic acid Glycidyl ester and triethylamine were stirred and reacted at room temperature for 14 days. After the reaction was over, dialyzed with deionized water for 72 hours (molecular weight cut-off of the dialysis bag was 3500 Daltons), and then excessive dithiothreitol was added, and the reaction was carried out at room temperature. Stir for 10 hours, then dialysis and purify with deionized water for 72 hours (the molecular weight cut-off of the dialysis bag is 3500 Daltons), and finally freeze-dry to obtain the hyaluronic acid (GM-HA-SH ); wherein the molar ratio of cystamine-bound hyaluronic acid, glycidyl methacrylate, triethylamine and dithiothreitol is 1:20:20:5. The reaction process diagr...

Embodiment 3

[0055] Example 3 Preparation of Multifunctional Hyaluronic Acid (Z-HA-SH)

[0056] Preparation of carboxybetaine methacrylate monomer by ring-opening reaction of 2-(dimethylamino)ethyl methacrylate and β-propiolactone. The specific method is:

[0057] ①Dissolve 30mmol of 2-(dimethylamino)ethyl methacrylate in 150ml of anhydrous acetone;

[0058] ②Under nitrogen protection conditions, dissolve 36mmol of β-propiolactone in 30ml of anhydrous acetone;

[0059] ③ Add the solution obtained in step ② dropwise to the solution obtained in step ①, keep the dropping rate at 1 drop / second, control the dropping time within 15 minutes, then stir and react for 5 hours, and use an ice bath to reduce the temperature of the reaction system during the entire reaction process. Keep at 10°C;

[0060] ④ After the reaction, use anhydrous acetone to precipitate the product, and use anhydrous acetone and anhydrous ether to wash alternately for several times, and then dry it in a vacuum oven to obta...

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Abstract

The invention discloses a preparation method of microenvironment-sensitive drug-loading nano capsules with tumor cell biological reducibility. The preparation method comprises the following steps: (1) preparing cystamine combined hyaluronic acid; (2) preparing esterified cystamine combined hyaluronic acid; (3) preparing multifunctional hyaluronic acid (Z-HA-SH); (4) preparing amino folic acid; (5) preparing a drug-loading nano capsule precursor; and (6) preparing the microenvironment-sensitive drug-loading nano capsules with tumor cell biological reducibility. The drug-loading nano capsules have good biocompatibility, no immunogenicity and high safety and can promote bioavailability of a drug, improve anti-tumor effect and reduce toxic and side effects on normal tissues.

Description

technical field [0001] The invention belongs to the technical field of biomedical materials, and in particular relates to a drug-loaded nanocapsule sensitive to the bioreductive microenvironment of tumor cells and a preparation method thereof. Background technique [0002] Chemotherapy (Chemotherapy, referred to as chemotherapy) provides a feasible means for the clinical treatment of malignant tumors, and also improves the survival rate of patients to a certain extent, but due to some shortcomings of the anti-tumor chemical drugs used in this strategy, such as Low water solubility, high toxicity, and lack of specific recognition of tumor sites have limited the clinical use of this method. Nano-drug carriers provide a way to solve this problem. The delivery of anti-tumor drug molecules through nano-drug carriers can avoid the above-mentioned shortcomings of the drugs themselves, while ensuring the safe transportation of drugs in the blood, improving their accumulation in tum...

Claims

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Application Information

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IPC IPC(8): A61K9/50A61K47/36A61K47/22A61K31/704A61P35/00
CPCA61K9/5036A61K31/704A61K47/22
Inventor 易强英马瑾康珂顾忠伟
Owner SICHUAN UNIV
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