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Polymer nanocarriers specifically targeting activated hepatic stellate cells with folic acid and their medicinal uses

A technology of hepatic stellate cells and nanocarriers, which is applied in the field of polymer nanocarriers targeting activated hepatic stellate cells and its preparation and application. Ligand polymer nanocarriers and other issues

Inactive Publication Date: 2018-09-21
SOUTHWEST JIAOTONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, there is no related report on folic acid ligand-coupled polymer nanocarriers specifically targeting hepatic stellate cells

Method used

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  • Polymer nanocarriers specifically targeting activated hepatic stellate cells with folic acid and their medicinal uses
  • Polymer nanocarriers specifically targeting activated hepatic stellate cells with folic acid and their medicinal uses
  • Polymer nanocarriers specifically targeting activated hepatic stellate cells with folic acid and their medicinal uses

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Effect test

Embodiment 1

[0028] Isolation and Culture of Primary Rat Hepatic Stellate Cells (HSC)

[0029] Rat liver was digested by in situ perfusion method, and the primary rat hepatic stellate cells obtained by digestion were placed in high-glucose DMEM medium (containing 15%-20% FBS, 1% double antibody P / S) at 37°C , 5% CO 2 cultured in a cell incubator.

Embodiment 2

[0031] Culture of Activated Rat Hepatic Stellate Cells (HSC-T6)

[0032] After recovery and passage of HSC-T6 cells, add high-glucose DMEM medium (containing 10% FBS, 1% double antibody P / S) and place at 37°C, 5% CO 2 cultured in a cell incubator.

Embodiment 3

[0034] Analysis of mRNA expression changes of primary rat hepatic stellate cells (HSC) from resting state to activated state αSMA, Collagen1a1, FR-α

[0035] Rat liver was digested by in situ perfusion method, and the primary rat hepatic stellate cells obtained from the digestion were cultured in a 24-well plate for 7 days, and then the culture medium of the 24-well plate was aspirated, washed twice with PBS, and the PBS was discarded . Axygen kit was used to extract primary rat hepatic stellate cell RNA, reverse transcription kit and QPCR instrument were used to reverse transcribe the RNA into cDNA and dilute it, and then perform PCR to analyze the mRNA expression of αSMA, Collagen1a1 and FR-α Variety. The changes in mRNA expression are shown in Figure 1 (a, b, c).

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Abstract

The invention provides a polymer nanocarrier specifically targeting activated hepatic stellate cells with folic acid and its medicinal use. During the transition from resting state to myofibrosis-like activated state, the expression of α-type folate receptor in hepatic stellate cells was significantly enhanced. Further preparation of folic acid-coupled polymer nanomicelle carrier, we successfully achieved its specific targeting of activated primary rat hepatic stellate cells and cell lines. The drug nanocarrier system of the present invention adopts polyethylene glycol as the material of the hydrophilic segment to ensure its resistance to protein adsorption and cell adhesion in blood circulation; polycaprolactone is used as the nucleation material of the hydrophobic segment, which is convenient for various Loading of hydrophobic anti-fibrotic drugs and fluorescent dyes. The folic acid coupled to the PEG shell ensures that the carrier system can specifically recognize the folic acid receptors on the surface of activated hepatic stellate cells, and finally effectively improves the utilization rate of the drug and reduces its toxic and side effects.

Description

technical field [0001] The invention belongs to the field of drug delivery. It specifically relates to a polymer nanocarrier targeting activated hepatic stellate cells and its preparation and application. Background technique [0002] my country is a high-incidence area for liver diseases such as liver fibrosis, liver cirrhosis, and liver cancer. The incidence and mortality of liver cancer exceed 50% of the world's total. There is a positive correlation between the incidence of liver cirrhosis and liver cancer. As an important early disease of liver cirrhosis, liver fibrosis has attracted more and more attention from researchers. The formation of liver fibrosis involves hepatocytes (HC), hepatic stellate cells (HSC), lacunae cells, Kupffer cells (KC) and liver sinusoidal endothelial cells (SLEC), etc. Hepatic stellate cells (HSCs) after state transition are considered to be the central link in the initiation process of liver fibrosis. With the development and application ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K9/51A61K47/34A61K47/10A61K47/22A61K45/06A61P1/16
CPCA61K9/1075A61K45/06A61K47/22A61K47/34
Inventor 陈渝萍程江张艳军汪辛
Owner SOUTHWEST JIAOTONG UNIV
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