Preparation method of antagonist functionalized poly-L-lactic acid porous microspheres

A technology of poly-L-lactic acid and porous microspheres, which is applied in the direction of anti-inflammatory agents, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problems of poor hydrophilicity, increase the load capacity, and improve Effects of drug concentration, inhibition of cellular inflammatory gene expression and factor secretion

Active Publication Date: 2020-12-29
THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Aiming at the disadvantage of poor hydrophilicity of PLLA, the surface was modified by alkaline hydrolysis to expose the active carboxyl groups on the surface of the microspheres, while the surface of the BSA nanoparticles w

Method used

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  • Preparation method of antagonist functionalized poly-L-lactic acid porous microspheres
  • Preparation method of antagonist functionalized poly-L-lactic acid porous microspheres
  • Preparation method of antagonist functionalized poly-L-lactic acid porous microspheres

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Embodiment 1

[0026] The preparation of the BSA nanoparticle of embodiment 1 load antagonist

[0027]Add 100 mg of BSA to 10 mL of deionized water and stir evenly, then add 10 μg of antagonist dissolved in phosphate buffer; pump 40 mL of ethanol into the BSA solution containing antagonist at a flow rate of 2 mL / min, and stir overnight at room temperature; Add 40mL of chitosan solution dissolved in 1% acetic acid solution with a concentration of 1mg / mL to the above mixture; then pump in ethanol at a flow rate of 0.5mL / min, stir at room temperature for 8h; centrifuge the obtained nanoparticles at 12000rpm for 20min , washed three times with 50% ethanol solution to prepare antagonist-loaded BSA nanoparticles.

Embodiment 2

[0028] The preparation of embodiment 2 L-polylactic acid porous microspheres

[0029] PLLA was dissolved in dichloromethane, gelatin and polyvinyl alcohol PVA were dissolved in deionized water to make solutions with final concentrations of 2wt%, 7.5wt%, and 1wt% respectively; 1g gelatin and PVA mixed solution was added to 3g PLLA solution , ultrasonically mixed (power 10%, ultrasonic 2s, interval 1s), as an emulsion.

[0030] The microfluidic device for preparing microspheres is a coaxial needle with dual channels, the inner and outer diameters are (0.26mmi.dx0.51mm o.d, 0.84mm i.d x1.27 mm o.d, 25G / 18G), and the end of the needle is connected to PVC tubing for collection; a syringe loaded with emulsion as the discontinuous phase, connected to the inner diameter of the device; a continuous phase of 1% PVA solution, connected to the outer diameter of the device, and the flow rate of the two was set at 20:1 to make it continuous Run until the emulsion is used up; collect the mi...

Embodiment 3

[0031] Example 3 Preparation of antagonist-functionalized poly-L-lactic acid porous microspheres

[0032] Ultrasonically disperse the L-polylactic acid porous microspheres prepared in Example 2 into 5 mL of MES (pH=6.0) buffer, add 40 mg of EDC and 60 mg of NHS respectively, ultrasonicate for 15 s, react at 37°C for 15 min, centrifuge and discard the supernatant solution; the antagonist-loaded BSA nanoparticles prepared in Example 1 were dispersed in 10 mL of deionized water, the centrifuged EDC-activated microspheres were added to it, and ultrasonically mixed; reacted overnight at 37°C, and finally centrifuged again. The antagonist-functionalized L-polylactic acid porous microspheres were obtained by repeated washing three times with deionized water.

[0033] figure 1 A and B are the flow charts for the preparation of the microspheres of the present invention, figure 1 In A, the PLLA microspheres were treated with alkaline solution to expose the surface carboxyl groups, fi...

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Abstract

The invention discloses a preparation method of antagonist functionalized poly-L-lactic acid porous microspheres. The preparation method comprises the following steps: (1) preparing antagonist-loadedBSA nanoparticles; (2) preparing poly-L-lactic acid porous microspheres: taking L-polylactic acid, gelatin and polyvinyl alcohol as raw materials, preparing the microspheres by using a microfluidic device, treating the microspheres in alkaline water, and cleaning the microspheres with deionized water to obtain the poly-L-lactic acid porous microspheres; and (3) preparing the antagonist functionalized poly-L-lactic acid porous microspheres: coupling BSA nanoparticles loaded with an antagonist with the poly-L-lactic acid porous microspheres by adopting an EDC/NHS method to prepare the antagonistfunctionalized L-polylactic acid porous microspheres. A series of material science tests, cell experiments and in-vivo experiments prove that the porous microspheres have good biocompatibility and anti-inflammatory performance, extracellular matrix metabolic imbalance caused by inflammation is corrected, and tissue function recovery is promoted.

Description

technical field [0001] The invention belongs to the technical field of functional materials, and in particular relates to a preparation method of antagonist-functionalized L-polylactic acid porous microspheres. Background technique [0002] For a long time, the inflammatory response has played an important role in chronic non-infectious diseases, triggering cascade reactions through a series of signaling pathways, and participating in the occurrence of diseases in multiple systems and organs [1-5] . In clinical practice, a variety of treatment methods have been developed for inflammatory reactions, such as gene therapy, hormone therapy, etc. [6] . However, the effect of gene therapy has yet to be investigated due to the large number of genes involved in the inflammatory response and the low transfection rate [7] . However, because of the many side effects caused by hormone therapy, medical workers should be cautious when using it. [8] . In the inflammatory response, th...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/59A61K9/51A61K47/42A61K45/00A61P29/00A61P19/08
CPCA61K47/6941A61K47/593A61K9/5169A61K45/00A61P29/00A61P19/08
Inventor 陈亮顾勇崔文国蔡峰许眙昌
Owner THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIV
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