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Delivery system based on miRNA-34a micromolecule regulator and preparation method and application of delivery system

A delivery system and modulator technology, applied in the field of biomedicine, can solve problems such as poor water solubility, achieve the effects of improving stability, avoiding easy degradation, and good clinical application value

Inactive Publication Date: 2016-05-04
BEIJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The nano-micelle provided by the present invention can more efficiently carry the miRNA-34a small molecule regulator Rubone, solve the problem of Rubone's poor water solubility, and improve its solubility

Method used

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  • Delivery system based on miRNA-34a micromolecule regulator and preparation method and application of delivery system
  • Delivery system based on miRNA-34a micromolecule regulator and preparation method and application of delivery system
  • Delivery system based on miRNA-34a micromolecule regulator and preparation method and application of delivery system

Examples

Experimental program
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Effect test

Embodiment 1

[0043] Example 1 Carboxymethyldextran (substitution degree>50%, molecular weight 20-110KDa) modified polyethyleneimine-polycaprolactone (wherein the molecular weight of polyethyleneimine is 800Da, and the molecular weight of polycaprolactone is 20KDa ) preparation of wrapped Rubone nano micelles

[0044] (a) Place 1mg of Rubone and 20mg of polyethyleneimine-polycaprolactone copolymer (wherein the molecular weight of polyethyleneimine is 800Da, and the molecular weight of polycaprolactone is 20KDa) in a centrifuge tube, at room temperature Add 2 mL of chloroform and sonicate to dissolve it completely. Then add 4mL of emulsifier polyvinyl alcohol (PVA, 1%, w / w) and block polyether (F68, 1%, w / w) aqueous solution, vortex for 30s, and then use a cell disruptor to sonicate for 5min. Pour the mixed solution of the organic phase and the aqueous phase in the centrifuge tube into a round-bottomed flask, and rotate it with a rotary evaporator for 10-30 min until the organic solvent is ...

Embodiment 2

[0048] Example 2 Test the release of Rubone from the nano-delivery system in pH=7.4 buffer solution

[0049] The in vitro release curve can be measured by simulating the release process of Rubone from the nano-delivery system in vitro. The pharmaceutical composition prepared in Example 1 was dispersed in 2 mL of PBS, and the dispersion was placed in a dialysis bag with a molecular weight cut off of 3000 Da. The dialysis bag was placed in a mixed solvent of 9 mL of pH=7.4 sulfate buffer solution and 1 mL of acetonitrile. The whole system was incubated at 110 rpm on a shaker at 37° C. in the dark. Take 500 μL of the solution outside the dialysis bag within the specified time, and supplement 500 μL of corresponding PBS. The concentration of Rubone was tested with an ultraviolet spectrophotometer, the cumulative release rate of Rubone in the nano-delivery system was calculated at each time point, and the corresponding release kinetic curve was drawn.

[0050] image 3 It is th...

Embodiment 3

[0051] Example 3 Carboxymethyl dextran (substitution degree>50%, molecular weight 20-110KDa) modified polyethyleneimine-polycaprolactone (wherein the molecular weight of polyethyleneimine is 800Da, polycaprolactone) loaded with Rubone Detection Experiment of Proliferation Toxicity of Ester Nanomicelles with Molecular Weight of 20KDa on HepG-2 Cells

[0052] (1) HepG-2 cells in the logarithmic growth phase were collected and seeded in a 96-well plate, with the number of cells per well being 1×10 4 were cultured overnight to allow the cells to adhere to the wall.

[0053] (2) Polyethyleneimine-polycaprolactone (wherein the molecular weight of polyethyleneimine is 800Da) modified with carboxymethyl dextran (substitution degree>50%, molecular weight 20-110KDa) loaded with Rubone , the molecular weight of polycaprolactone is 20KDa) nanomicelles are mixed with RPMI1640 medium of 10% (v / v) FBS, and the concentration of Rubone is set to be 20 μM.

[0054] (3) Remove the serum-contai...

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Abstract

The invention relates to a nanometer delivery system based on miRNA-34a micromolecule regulator and a preparation method and application of the delivery system. The delivery system comprises a nanometer delivery system body and the miRNA-34a micromolecule regulator loaded on the nanometer delivery system body. Polyethyleneimine-polycaprolactone nanomicelles modified by carboxymethyl glucosan are used as carriers, and the miRNA-34a micromolecule regulator is regulated from a hydrophobic small molecule compound 2'-hydroxyl-2,3,4',5,6'-pentamethoxyl chalcone which has liver-cancer-resistant activity and is also named as Rubone. By means of the delivery system, Rubone can be entrapped in a high-efficiency mode, the physicochemical property of Rubone is improved, the miRNA-34a micromolecule regulator can be delivered into liver cancer cells without using organic solvent, expression of miRNA-34a with the tumor restraining function in the cells is improved, proliferation of liver cancer cells can be effectively restrained, and it is further verified through a naked mouse liver cancer tumor transplantation model that growth of liver cancer can be remarkably retrained by injecting the nanomicelles in caudal veins.

Description

technical field [0001] The present invention relates to the field of biomedicine, in particular to the application of nano-carrier materials in tumor treatment, and in particular to a nano-delivery system based on miRNA-34a small molecule modulator and its preparation method and application. Background technique [0002] Cancer is a major disease that seriously endangers human life and health. In recent years, the incidence rate has continued to increase, and the mortality rate has continued to increase. Primary liver cancer, referred to as liver cancer, generally has no obvious symptoms, especially in the early stages of the disease. Once the symptoms appear, it means that the tumor is already large, and its apoptosis progresses very rapidly. It usually presents cachexia within a few weeks, and often fails and dies within a few months to a year. Conventional chemotherapeutic drugs for liver cancer include 5-fluorouracil, oxaliplatin, paclitaxel, etc., which are often accom...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/34A61K31/122A61P35/00
CPCA61K9/1075A61K31/122A61K47/34
Inventor 盛望尹朝霞邓雄威王怡慧张芳曾毅
Owner BEIJING UNIV OF TECH
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