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A preparation method of antagonist functionalized poly-L-lactic acid porous microspheres

A technology of poly-L-lactic acid and porous microspheres, which can be used in the direction of anti-inflammatory agents, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., and can solve problems such as poor hydrophilicity

Active Publication Date: 2022-06-21
THE FIRST AFFILIATED HOSPITAL OF SOOCHOW UNIV
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  • Summary
  • 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 wrapped with the antagonist was rich in amino groups due to the chitosan content, and the carbodiimide method was used to form Grafting of amide bonds to construct antagonist-functionalized injectable PLLA porous microspheres

Method used

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

Examples

Experimental program
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Embodiment 1

[0026] Example 1 Preparation of antagonist-loaded BSA nanoparticles

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

Embodiment 2

[0028] Example 2 Preparation of L-polylactic acid porous microspheres

[0029] Dissolve PLLA in dichloromethane, and dissolve gelatin and polyvinyl alcohol PVA in deionized water to prepare solutions with final concentrations of 2wt%, 7.5wt%, and 1wt% respectively; add 1g of gelatin and PVA mixed solution to 3g of PLLA solution , ultrasonic mixing (power 10%, ultrasonic 2s, interval 1s), as emulsion.

[0030] The microfluidic device for preparing microspheres is a coaxial needle with dual channels, the inner and outer diameters are respectively (0.26mmi.dx0.51mm o.d, 0.84mm i.d x1.27mm o.d, 25G / 18G), and the end of the needle is connected PVC tubing for collection; syringe loaded with emulsion as discontinuous phase, connected to the inner diameter of the device; continuous phase, a 1% PVA solution, connected to the outer diameter of the device, with flow rates set to 20:1 to make it continuous Run until the emulsion is used up; the microspheres are collected in a 500 mL beak...

Embodiment 3

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

[0032] The L-polylactic acid porous microspheres prepared in Example 2 were ultrasonically dispersed in 5 mL of MES (pH=6.0) buffer, 40 mg of EDC and 60 mg of NHS were added, ultrasonicated for 15 s, and the supernatant was discarded by centrifugation after reacting at 37 °C for 15 min. Disperse the antagonist-loaded BSA nanoparticles prepared in Example 1 in 10 mL of deionized water, add the centrifuged EDC-activated microspheres into it, and mix by ultrasonic; react overnight at 37 °C, and finally centrifuge again, The antagonist-functionalized L-polylactic acid porous microspheres were prepared by repeatedly washing with deionized water for three times.

[0033] figure 1 A, B are the preparation flow chart of the microsphere of the present invention, figure 1 The PLLA microspheres in A are treated with lye to expose the surface carboxyl groups, figure 1 B shows that the amin...

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Abstract

The invention discloses a preparation method of antagonist-functionalized poly-L-lactic acid porous microspheres, comprising the following steps: (1) preparation of BSA nanoparticles loaded with antagonist; (2) preparation of poly-L-lactic acid porous microspheres: Using L-lactic acid, gelatin and polyvinyl alcohol as raw materials, microfluidic devices are used to prepare microspheres; then the microspheres are treated in alkaline water, and then cleaned with deionized water to obtain poly-L-lactic acid porous microspheres; (3) Preparation of antagonist-functionalized L-polylactic acid porous microspheres: BSA nanoparticles loaded with antagonists were coupled with L-polylactic acid porous microspheres by EDC / NHS method to prepare antagonist-functionalized L-polylactic acid microspheres. Lactic acid porous microspheres. A series of material tests, cell experiments and in vivo experiments have proved that the porous microsphere has good biocompatibility and anti-inflammatory properties, corrects the imbalance of extracellular matrix metabolism caused by inflammation, and promotes the recovery of tissue function.

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] Inflammation has always 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 the inflammatory response, such as gene therapy, hormone therapy, etc. [6] . However, due to the large number of genes involved in the inflammatory response and the low transfection rate, the effect of gene therapy remains to be investigated [7] . Hormone therapy has caused medical workers to be cautious when using it because of its many side effects. [8] . In the inflammatory response, the increase in the concentration...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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