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Neutrophil extracellular sterilization network responsive drug-loaded gel and preparation method and application method thereof

A neutrophil, responsive technology, applied in the field of neutrophil extracellular bactericidal network responsive drug-loaded hydrogel and its preparation, achieves advantages of clinical application, correction of high immunosuppressive effect, and convenient and simple implantation method Effect

Active Publication Date: 2022-03-01
CHINA PHARM UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

No drug-loaded hydrogels for local delivery of NETs

Method used

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  • Neutrophil extracellular sterilization network responsive drug-loaded gel and preparation method and application method thereof
  • Neutrophil extracellular sterilization network responsive drug-loaded gel and preparation method and application method thereof
  • Neutrophil extracellular sterilization network responsive drug-loaded gel and preparation method and application method thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Embodiment 1: preparation of drug-loaded hydrogel

[0025] The drug-loaded hydrogel responsive to neutrophil extracellular bactericidal network of the present invention, the drug-loaded hydrogel includes positively charged histones and negatively charged sodium alginate, wherein the positively charged histones are H2A, H2B, H3 or H4 .

[0026] The steps of the preparation method of neutrophil extracellular bactericidal network-responsive drug-loaded hydrogel of the present invention: (1) Precipitation plasticity method is used to prepare hydrogel patch, and 1 mL of 10 mg / mL histone aqueous solution is slowly added dropwise to In 1mL of sodium alginate aqueous solution with a concentration of 10mg / mL, precipitation occurs rapidly due to the strong electrostatic interaction between polyelectrolytes.

[0027] (2) The white precipitate was collected by centrifugation under the action of 15000g centrifugal force for 5 minutes, and molded into a sheet-shaped polymer composit...

Embodiment 2

[0029] Embodiment 2: In vitro gel degradation experiment

[0030] The prepared hydrogel patch was freeze-dried for 24 hours and weighed, then immersed in water at 4°C for 24 hours to reach a state of swelling equilibrium, and then weighed after wiping off the surface moisture. The water content of the hydrogel is calculated by the following formula Qe=(M1-M2) / M1*100%. Among them, M1: the weight of the hydrogel after absorbing water and saturating it in water for 48 hours, after the filter paper absorbs the surface moisture; M2: the weight of the hydrogel freeze-dried to constant weight. The prepared hydrogel patch has a moisture content of 75.5%

[0031] The monoclonal antibody drug loading was carried out by dry soaking method. The prepared hydrogel patch was immersed in an aqueous solution containing 2 mg / mL TGF-β monoclonal antibody. Stand at 4°C for 24 hours to reach a state of swelling equilibrium. The BCA kit was used to measure the drug concentration in the supernat...

Embodiment 3

[0034] Embodiment 3: Hydrogel degradation experiment in animal model

[0035] Construct breast cancer orthotopic model, the tumor grows to 200mm 3 , for postoperative resection (retaining 10% of the tumor to simulate postoperative residual). The postoperative mouse models were divided into three groups, histone sodium alginate hydrogel group (SA-H), chitosan sodium alginate hydrogel group (SA-C) and histone sodium alginate hydrogel group Mouse neutrophil depletion group (SA-H, neutrophildepletion). The material was implanted into the postoperative cavity, and the material was taken out 1, 3, 7, and 14 days after the operation, weighed, and the internal structure was observed by SEM.

[0036] like image 3 As shown, histone sodium alginate hydrogel degraded 78.8% in 14 days after breast cancer mouse model, chitosan sodium alginate hydrogel degraded 19.8% in the control group, neutrophil depletion group 12.7% degradation.

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Abstract

The invention discloses a neutrophil extracellular sterilization network responsive drug-loaded hydrogel as well as a preparation method and a use method thereof. The drug-loaded hydrogel comprises electropositive histone and electronegative sodium alginate, the preparation method comprises the following steps: slowly dropwise adding a histone aqueous solution into a sodium alginate aqueous solution, and rapidly precipitating the solution; and collecting the white precipitate, shaping the white precipitate into a flaky polymer compound, and standing until the polymer compound becomes almost transparent, thereby obtaining the hydrogel. The used materials are high in biocompatibility, the preparation conditions are simple and mild, hydrogel material degradation is achieved through the tumor postoperative physiological process, NETs local drug release is achieved, and therefore the local high immunosuppression effect of NETs is corrected; meanwhile, the hydrogel drug delivery system has the tumor metastasis resisting curative effect superior to that of free drugs, the postoperative implantation mode is convenient and simple, and clinical application is facilitated.

Description

technical field [0001] The invention relates to the fields of nanomaterial preparation and biomedicine, in particular to a neutrophil extracellular bactericidal network-responsive drug-loaded hydrogel and a preparation method and application method thereof. Background technique [0002] Surgical resection is the main treatment for malignant tumors. After surgical resection of tumors, various growth factors and cytokines are released from damaged tissues during surgery to promote inflammatory responses and damage repair, but some of these factors can also promote tumor growth. These factors lead to tumor recurrence in situ after resection and can also promote the formation of distant metastases. [0003] In the inflammatory state, neutrophils will release arginine deiminase, which will promote the citrullination of arginine in the histone structure bound to DNA, making the positively charged histones become electrically neutral, and the chromosome will decompose. Polymeriza...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/42A61K47/36A61K45/00A61P35/00A61P35/04
CPCA61K9/06A61K47/42A61K47/36A61K45/00A61P35/00A61P35/04
Inventor 柳文媛曲玮祝婉芳刘富垒冯锋韩凌飞
Owner CHINA PHARM UNIV
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