Macrophage-mediated drug-loaded hyaluronic acid nanohydrogel and preparation thereof

A nano-hydrogel and hyaluronic acid technology is applied in the field of drug-loaded nanomaterials and their preparation to achieve good tumor treatment effect, increase accumulation, and reduce endocytosis.

Active Publication Date: 2020-05-08
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Retrieval of related literature and patents at home and abroad shows that macrophage-mediated hyaluronic acid nanohydrogels loaded with polypyrrole and doxorubicin for targeted delivery of drugs have not been reported yet.

Method used

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  • Macrophage-mediated drug-loaded hyaluronic acid nanohydrogel and preparation thereof
  • Macrophage-mediated drug-loaded hyaluronic acid nanohydrogel and preparation thereof
  • Macrophage-mediated drug-loaded hyaluronic acid nanohydrogel and preparation thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0066] Dissolve hyaluronic acid sodium salts (20mg) with different molecular weights (48kDa, 320kDa, 950kDa, Bloomage) in 2mL of ultrapure water, add EDC (HA:EDC=1:0.5, molar ratio), magnetic The reaction was stirred for 3 h to activate the carboxyl groups on HA. The surfactant AOT (134 mg) was pre-dissolved in 4 mL of dichloromethane DCM, and then the activated HA / EDC solution was added dropwise to the AOT / DCM solution with stirring, and stirred for 10 min to form a milky white W / O emulsion , and then added the solution dropwise into a pre-dissolved PVA aqueous solution (2wt%, 30mL), and continued to stir for 15min to form a milky white W / O / W double emulsion. Finally, the cross-linking agent Cys (22.4mg, 1mL) was added to react for 1h, and then ultrasonicated in an ice bath for 10min with a sonicator, and then the bottle was opened and stirred overnight in a fume hood to completely evaporate the organic solvent DCM. The next day, the HA NGs aqueous solution was dialyzed for ...

Embodiment 2

[0070] The HA NGs, HA@PPy NGs and HA / DOX@PPy NGs prepared in Example 1 were characterized. The hydrodynamic particle size distribution and potential changes of HA NGs prepared from hyaluronic acid with different molecular weights are as follows: figure 2 As shown in a and 2b, as the molecular weight of HA increases (48, 320, 950kDa), the hydrodynamic particle size of the prepared HA NGs increases from 243.77nm to 316.67nm and 383.0nm respectively, and the surface potential also increases slightly . However, in the process of preparing HA NGs, it was found that when the molecular weight of HA reaches 950kDa, due to its high viscosity, demulsification is prone to occur during the W / O / W emulsification process. Therefore, 48kDa and 320kDa HA NGs were selected for subsequent research on PPy loading. The results are as follows: figure 2 c, 2d and Table 1, with the increase of the mass ratio of pyrrole monomer Py (HA:Py=1:0.11,1:0.23,1:0.46,1:0.69,1:0.92), the prepared HA@PPy NGs...

Embodiment 3

[0078] The drug release results of drug-loaded nanogel HA / DOX@PPy NGs (350kDa, HA:Py=1:0.46) are as follows Figure 5 as shown in a. The citric acid buffer solution with pH=5.0 and the phosphate buffer solution with pH=7.4 were respectively selected as sustained-release media to investigate the release performance of DOX in different pH environments. First, weigh 1 mg HA / DOX@PPy NGs and dissolve them in 1 mL of the corresponding buffer solution, place them in cellulose membrane dialysis bags with MWCO=14000, and suspend them in 9 mL of PBS solution (pH= 7.4) or citric acid buffer solution (pH=5.0) in a 50mL centrifuge tube, the total volume of the solution in the centrifuge tube is 10mL, each sample has 3 parallels, and then placed in a constant temperature shaker at 37°C for shaking. At the set time point, take 1 mL of sustained-release solution in the EP tube, measure its UV-Vis absorption value at 490 nm, and add 1 mL of new buffer solution at the same time to keep the tot...

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Abstract

The invention relates to a macrophage-mediated drug-loaded hyaluronic acid nanohydrogel and preparation thereof. A drug-loaded hyaluronic acid nanohydrogel is obtained by synthesizing polypyrrole in situ from the interior of a hyaluronic acid nanohydrogel, and loading a drug; and the macrophage-covered drug-loaded nanohydrogel is obtained by performing co-incubation on the drug-loaded hyaluronic acid nanohydrogel and mouse macrophages. The macrophage-mediated drug-loaded nanohydrogel prepared by the method has the advantages of low toxicity, safety, avoidance of phagocytosis of a reticuloendothelial system, and specific targeting in tumor areas when used for delivery of anti-cancer drugs, and has potential application prospects in tumor treatment.

Description

technical field [0001] The invention belongs to the field of drug-loaded nanometer materials and preparation thereof, in particular to a drug-loaded hyaluronic acid nano hydrogel mediated by macrophages and its preparation. Background technique [0002] Cancer is one of the important diseases that threaten human life and health around the world. Early diagnosis, early detection and early treatment will greatly increase the chance of cancer cure. The current conventional methods for treating cancer include surgery, chemotherapy, radiotherapy, immunotherapy, etc. Chemotherapy, as the main means of adjuvant cancer treatment before and after surgery, still has the disadvantages of lack of specificity, poor water solubility, low cell permeability, and strong resistance to normal tissue cells. Disadvantages such as side effects. Thanks to the rapid development of nanomedicine technology, in order to overcome the limitations of conventional cancer treatment methods, various types ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/36A61K47/46A61K41/00A61K31/704A61P35/00
CPCA61K9/5161A61K9/5176A61K31/704A61K41/0052A61P35/00A61K2300/00
Inventor 史向阳肖婷婷
Owner DONGHUA UNIV
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