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Nano-engineered stem cell anti-tumor targeting drug delivery system as well as preparation method and application thereof

A drug delivery system and stem cell technology, which are used in antitumor drugs, pharmaceutical formulations, and medical preparations with non-active ingredients to avoid toxicity, ensure integrity, and increase sensitivity.

Active Publication Date: 2022-08-05
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention aims at the problem of the influence of chemotherapeutic drugs on MSCs cell activity and function in the prior art, and provides a nano-engineered stem cell anti-tumor targeted drug delivery system; also provides a preparation method and application of the above drug delivery system

Method used

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  • Nano-engineered stem cell anti-tumor targeting drug delivery system as well as preparation method and application thereof
  • Nano-engineered stem cell anti-tumor targeting drug delivery system as well as preparation method and application thereof
  • Nano-engineered stem cell anti-tumor targeting drug delivery system as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Synthesis and Characterization of Maleimide Modified Polylactic Acid-Glycolic Acid Copolymer (PLGA-MAL)

[0047] 1 mg of PLGA-OH, 4 mg of BMPS, and 6 mg of EDCI were dissolved in 4 mL of dichloromethane (DCM), and the reaction system was magnetically stirred at room temperature under nitrogen protection for 24 h. The reaction solution was taken to check whether the product was formed by TLC method, and a GF254 silica gel thin-layer chromatography plate was used, and the developing solvent was methanol / chloroform (1:1, V / V). The dichloromethane was removed by rotary evaporation under reduced pressure, and the product was collected. At the end of the reaction, the reaction system was washed with water three times, and the organic layer was collected and dried under vacuum to obtain the final PLGA-MAL product. figure 1 It is the H NMR spectrum of PLGA-MAL. It can be seen that the characteristic peaks of PLGA (δ1.48-1.50ppm, δ4.10-5.35ppm) and the proton peak of maleimide ...

Embodiment 2

[0049] Preparation and Characterization of PLGA-MAL / (MET+PTX) Nanoparticles

[0050] Double drug-loaded PLGA-MAL / (MET+PTX) nanoparticles were prepared by W / O / W double emulsion solvent diffusion method. Precisely weighed recipe quantity 4mg PTX and 20mg PLGA-MAL dissolved in organic solvent as oil phase; Precisely weigh recipe quantity 4mg MET dissolved in 0.1% P188 aqueous solution as inner water phase; take 1% P188 solution as outer water phase. Under the vortex, the inner water phase was added dropwise to the oil phase with a 0.5mm needle syringe, and the ice bath probe was sonicated to form W / O colostrum; under magnetic stirring, the colostrum was added dropwise to the outer layer with a 0.5mm needle syringe. In the aqueous phase, the ice bath probe was sonicated to form a W / O / W double emulsion. The organic solvent was removed by rotary evaporation under reduced pressure; ultrafiltration (4°C, 3500rpm, 30min) was used to wash 3 times to remove free drug and excess P188, an...

Embodiment 3

[0052] In vitro serum stability of PLGA-MAL / (MET+PTX) nanoparticles

[0053] In this patent, the nanoparticles are bound to the cell membrane, and the drug-loaded PLGA-MAL / (MET+PTX) nanoparticles are carried by MSCs as cell carriers to achieve tumor-targeted drug delivery. To maintain stability during the process, the environment containing 10% fetal bovine serum was used to simulate the in vivo environment in vitro to investigate the particle size stability of PLGA-MAL / (MET+PTX) nanoparticles during incubation. The result is as image 3 As shown, with the prolongation of the incubation time, the particle size of the nanoparticles fluctuated up and down, the particle size changes were all less than 20%, and the PDI was less than 0.2, indicating that the in vitro serum stability of the nanoparticles was good.

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Abstract

The invention discloses a nano-engineered stem cell anti-tumor targeted drug delivery system, a preparation method and application, the targeted drug delivery system is composed of a delivery drug, a nano drug delivery carrier and stem cells, the stem cells are mesenchymal stem cells MSCs, the delivery drug is paclitaxel (PTX) and metformin hydrochloride (MET), the nano drug delivery carrier is a nano-engineered stem cell anti-tumor targeted drug delivery system, and the nano-engineered stem cell anti-tumor targeted drug delivery system is a nano-engineered stem cell anti-tumor targeted drug delivery system. Thioether bonds are covalently bound to the surfaces of MSCs (mesenchymal stem cells) to construct a nanoparticle-mesenchymal stem cell drug delivery system for targeted therapy of spinal glioma; the drug delivery system can retain tumor tropism and tumor infiltration capacity of MSCs, can effectively inhibit tumor cell growth in vivo and in vitro, promotes tumor cell apoptosis, and achieves a good anti-tumor effect.

Description

technical field [0001] The invention relates to a cell therapy and a nanometer drug delivery system, in particular to a preparation method and application of an engineered stem cell antitumor targeted drug delivery system. Background technique [0002] Intramedullary spinal cord tumor (IMSCT) is a rare malignant tumor in the central nervous system, accounting for about 4-10% of central nervous system tumors. Spinal cord intramedullary gliomas originate from the spinal cord ectoderm and account for about 80% of spinal cord intramedullary tumors. Spinal gliomas are usually asymptomatic in their early stages, and by the time they can be detected medically, the tumor has grown to a considerable size. Spinal gliomas in the medullary can compress the spinal cord and cause neurological dysfunction, and severe cases can lead to death of the patient. Due to the particularity of the location, surgical resection is still the preferred treatment option at present. However, due to the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K9/51A61K47/46A61K31/337A61K47/34A61P35/00A61K31/155
CPCA61K31/337A61K31/155A61K47/6901A61K9/5068A61K9/5153A61P35/00A61K2300/00
Inventor 王伟唐璐刘贺宁谢梦颖
Owner CHINA PHARM UNIV
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