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Inflammatory microenvironment responsive smart drug-loaded hydrogel and preparation method and application thereof

A technology of microenvironment and drug-loaded micelles, applied in the field of medical materials, can solve the problems of hydrogel preparation with many components, single response of hydrogel, low solubility, etc., and achieve good rheological properties and good cytocompatibility , the effect of simple synthesis steps

Inactive Publication Date: 2020-07-24
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Aiming at the above problems in the prior art, the present invention provides an intelligent drug-loaded hydrogel that responds to the inflammatory microenvironment and its preparation method and application. The drug-loaded hydrogel can effectively solve the problem that the existing hydrogel is a single response Problems and existing hydrogels have many ingredients, resulting in low solubility, complex synthesis and high cost

Method used

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  • Inflammatory microenvironment responsive smart drug-loaded hydrogel and preparation method and application thereof
  • Inflammatory microenvironment responsive smart drug-loaded hydrogel and preparation method and application thereof
  • Inflammatory microenvironment responsive smart drug-loaded hydrogel and preparation method and application thereof

Examples

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Effect test

Embodiment 1

[0056] A method for preparing an intelligent drug-loaded hydrogel responsive to an inflammatory microenvironment, the preparation steps are as follows:

[0057] (1) Synthesis of phenylboronic acid modified alginate (ALG-BA)

[0058] Accurately weigh sodium alginate (ALG, 5.00g) and dissolve it in 500mL of MES buffer (0.1mol, pH5.0), add 1-ethyl-(3-dimethylaminopropyl)carbodiethylene Amine hydrochloride (EDC·HCl, 4.80 g, 25.0 mmol) and 3-aminophenylboronic acid (BA, 1.95 g, 12.5 mmol). Then, it was stirred at 37°C for 24 hours, and finally dialyzed in deionized water (pH7.4) for 3 days, and after 3 days, it was freeze-dried with a lyophilizer to obtain purified ALG-BA;

[0059] (2) Synthesis of cholesterol-modified hyaluronic acid (HA-CHOL)

[0060] HA (2.00g) and cholesterol (CHOL, 1.50g) were completely dissolved in dimethylsulfoxide (DMSO, 30mL) at 80°C, and N,N'-dicyclohexylcarbodiimide was added to it (DCC, 1.00g) and 4-dimethylaminopyridine (DMAP, 0.50g), stirring cont...

Embodiment 2

[0066] A method for preparing an intelligent drug-loaded hydrogel responsive to an inflammatory microenvironment, the preparation steps are as follows:

[0067] (1) Synthesis of phenylboronic acid modified hyaluronic acid (HA-BA)

[0068] Accurately weigh 5g of hyaluronic acid and dissolve in 500mL of MES buffer (0.1mol, pH 5.0), add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl , 4.80g, 25.0mmol) and one of 2-aminophenylboronic acid or 3-aminophenylboronic acid (BA, 1.95g, 12.5mmol), then stirred at 37°C for 24h, and finally in deionized water (pH7.4 ) was dialyzed for 3 days, and freeze-dried with a freeze dryer to obtain purified HA-BA;

[0069] (2) Amphiphilic drug carrier

[0070] Sodium alginate (2.00 g) and cholesterol (CHOL, 1.50 g) were completely dissolved in a mixed solution of dimethyl sulfoxide and water (DMSO, 30 mL), and N,N'-dicyclohexyl carbon was added thereto Diimine (DCC, 1.00g) and 4-dimethylaminopyridine (DMAP, 0.50g) were continuo...

Embodiment 3

[0076] A method for preparing an intelligent drug-loaded hydrogel responsive to an inflammatory microenvironment, the preparation steps are as follows:

[0077] (1) Synthesis of phenylboronic acid modified chitosan

[0078] Accurately weigh 5g chitosan and dissolve in 500mL MES buffer (0.1mol, pH 5.0), add EDC·HCl (4.80g, 25.0mmol) and 2-carboxyphenylboronic acid or 3-carboxyphenylboronic acid (BA, 1.95g , 12.5mmol) in one. Then, it was stirred at 37° C. for 24 h, and finally dialyzed in deionized water (pH 7.4) for 3 days. Freeze drying was performed using a freeze dryer.

[0079] (2) Amphiphilic drug carrier

[0080] The amphiphilic drug carrier directly selects polylactic acid-glycolic acid copolymer (PLGA) purchased by the company, which is polymerized by lactic acid and glycolic acid in a ratio of 50:50.

[0081] (3) Preparation of drug-loaded micelles

[0082] 10 mg of PLGA and an anti-inflammatory drug (ibuprofen, 1 mg) were dissolved in DMSO (10 mL), and then adde...

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Abstract

The invention provides an inflammatory microenvironment responsive smart drug-loaded hydrogel and a preparation method and application thereof. The preparation method for the inflammatory microenvironment responsive smart drug-loaded hydrogel comprises the following steps: a functional polymer containing ortho-hydroxyl reacts with phenylboronic acid containing amino or carboxyl to prepare a phenylboronic acid polymer; an amphiphilic drug carrier is prepared; the prepared amphiphilic drug carrier and a hydrophobic drug are dissolved with a good solvent, and then, water is added thereinto understirring to prepare a drug-loaded micellar solution; and the hydrophilic drug and the prepared phenylboronic acid polymer are dissolved in the prepared drug-loaded micellar solution, and then, the pHvalue of a mixed solution is regulated to 8-9 to prepare the smart drug-loaded hydrogel. The hydrogel responsively releases drugs through pH and reactive oxygen, and has the advantages that the preparation components are few and the synthesis operation is simple.

Description

technical field [0001] The invention belongs to the technical field of medical materials, and in particular relates to an intelligent drug-loaded hydrogel responsive to an inflammatory microenvironment, a preparation method and application thereof. Background technique [0002] Over the past few decades, hydrogels have been widely used in biomedical fields, such as tissue engineering scaffolds, cell culture substrates, and drug delivery vehicles. Although traditional hydrogels have the function of delivering drugs, they cannot achieve controlled release of drugs on demand in the disease microenvironment. Therefore, it has become a hotspot to develop a new type of smart hydrogel that can adjust its shape according to environmental changes for smart controlled release of drugs. Currently, stimuli-responsive smart hydrogels have attracted considerable attention for their potential applications in biomedicine. These smart hydrogels can rapidly release drugs in response to exte...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L26/00
CPCA61L26/008A61L26/0066A61L2300/626A61L2300/41
Inventor 王云兵胡成
Owner SICHUAN UNIV
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