Immune-enhanced exosome hydrogel compound as well as preparation method and application thereof

A technology of immune enhancement and exosomes, which is applied in the direction of non-active ingredients of polymer compounds, drug combinations, and pharmaceutical formulations, and can solve the problems of low tumor adhesion, weak retention, and low targeting efficiency of ordinary hydrogels. To achieve the effect of overcoming uneven distribution of drugs, enhancing dispersion stability, and improving dispersion stability

Active Publication Date: 2021-06-11
AFFILIATED HOSPITAL OF JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] Purpose of the invention: In order to solve the above technical problems, the present invention provides an immune-enhancing exosome hydrogel complex and its preparation method and application. The hydrogel complex is a brand-new chemotherapy + immune enhancer combination This solution can overcome the disadvantages of poor stability, low targeting efficiency, and weak retention of drug-l

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  • Immune-enhanced exosome hydrogel compound as well as preparation method and application thereof
  • Immune-enhanced exosome hydrogel compound as well as preparation method and application thereof
  • Immune-enhanced exosome hydrogel compound as well as preparation method and application thereof

Examples

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[0063] Example 1: Mannan peptide - hyallosan peptide - hyaluronic acid gel of hyaluronic acid hydride - Preparation and Characterization

[0064] (1) 10% fetal bovine serum high sugar DMEM medium and 1% double resistance conditions, in 5% CO 2 The 37 ° C constant temperature incubator culture mouse macrophages, the cells were completely attached and the growth was good, and 500 ng / ml LPS and 2 ng / mLIFN-γ were added, and 24 h-induced Raw264.7 macrophages were cultured induced by M1-polarized RAW264.7 macrophages. After absorbing the original medium, PBS was washed twice, and the serum-free high sugar DMEM medium was added, and 48 h was cultured. 100 ml of medium was collected, and the M1-macrophages were separated using ultra-velocity centrifocity: 4 ° C, 300 g centrifuge for 15 min, take it; 3000g centrifuge for 30 min, take it; 1 × PBS is resuspended with 1 × PBS 100,000 g of centrifugation 90min, precipitation was suspended with 100 μl of 1 × PBS, and the m1-macrophage popul...

Example Embodiment

[0069] Example 2: Preparation and Characterization of Gannaclosan peptide - hyaluronic acid hydrophilic gel induced by doxorubicin-M1 bone marrow source macrophage

[0070] (1) Take 4 to 6 weeks of age mice, PBS buffer rushing out of bone marrow, centrifugation; use ACK lysate red blood cells, DMEM medium centrifugation. Wash the floating cells, replace the new medium, replace the new medium, to obtain a new medium, to obtain a new medium, to obtain a mouse bone marrow source macrophage . 10% fetal bovine serum high sugar DMEM medium and 1% double resistance conditions, in 5% CO 2 The 37 ° C constant temperature incubator culture mouse macrophages, the cells were completely attached and the growth was good, and 500 ng / ml LPS and 2 ng / mL IFN-γ were added, and 24 h-induced bone marrow source macrophages were cultured induced by M1 polarization. After absorbing the original medium, PBS was washed twice, and the serum-free high sugar DMEM medium was added, and 48 h was cultured. 1...

Example Embodiment

[0073] Example 3: Dispersion Stability, Biological Safety, Degradation Performance and Explosive Curve of Examples

[0074] (1) Ultra-M1 Raw264.7 macrophages prepared in Example 1 were dispersed in the commercially available cross-linking hyaluronic acid gel (HA GEL, Hua Heo, Item No. TL100, China Patent In ZL2015101091144), Dox @ m1-exos-ha gel is prepared. In order to investigate the dispersion stability of DOX @ M1-EXOS in mannan peptide-hyaluronic acid hydrogel and ordinary cross-linking hyaluronic acid gel, will be configured in DOX @ M1-EXOS-HA-GEL and DOX @ m1 -EXOS-OHA / MAN GEL is placed at a 4 ° C refrigerator, and the sample is observed from 0D and 7D, such as Figure 9 As shown, the Dox @ m1-EXOS in a normal crosslinked hyaluronic acid gel is aggregated and precipitated, while the mannan peptide-hypocyanic acid hydrogel is uniform, speculative due to The surface mannose receptor in the surface of the macrophages has good affinity in the genite in the gel, significantly ...

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Abstract

The invention discloses an immune-enhanced exosome hydrogel compound as well as a preparation method and application thereof, the compound is prepared by the following steps: encapsulating a drug by an M1 type macrophage exosome to form a medicine-M1 type macrophage exosome, and then forming hydrogel through chemical crosslinking of mannatide and hyaluronic acid, and loading the medicine-M1 type macrophage exosome in the hydrogel to form the hydrogel medicine delivery system. The mannatide-hyaluronic acid hydrogel prepared by the invention not only has the advantages of acid-sensitive drug release, injectability, self-healing and the like of Schiff base type gel, but also has the effects of enhancing anti-tumor immunity, increasing exosome stability, tumor adhesiveness, biodegradability, biosafety and the like; and the drug-M1 type macrophage exosome can be slowly released after tumor local injection administration, and the drug-M1 type macrophage exosome can permeate into tumor and tumor inflammation areas in a targeted manner, so that tumor immunity is activated, and tumor is cooperatively killed.

Description

technical field [0001] The invention discloses an immune-enhancing exosome hydrogel complex, a preparation method and application thereof, and belongs to the technical field of hydrogel complexes. Background technique [0002] Malignant tumors seriously threaten human health, and existing treatment options such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy all have certain limitations. Although the combination therapy of chemotherapy and immunization has been commonly used in tumor therapy, it mostly adopts a systemic drug regimen, which has disadvantages such as low tumor selectivity, weak immune response efficiency, and high toxicity and side effects, which limit its clinical application. [0003] In recent years, local drug delivery to tumors, as an effective improvement scheme for systemic treatment, has become one of the research and development hotspots in the field of anti-tumor. Exosomes are nanovesicles secreted by cells with a bilayer...

Claims

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Application Information

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IPC IPC(8): A61K35/15A61K9/06A61K31/12A61K31/122A61K31/185A61K31/337A61K31/352A61K31/575A61K31/704A61K45/06A61K47/36A61K47/42A61P35/00A61P37/04
CPCA61K9/06A61K31/12A61K31/122A61K31/185A61K31/337A61K31/352A61K31/575A61K31/704A61K35/15A61K45/06A61K47/36A61K47/42A61P35/00A61P37/04A61K2300/00
Inventor 宋金方倪江叶琳岚马昂李霞丁永娟
Owner AFFILIATED HOSPITAL OF JIANGNAN UNIV
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