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Polymer nano-carrier for folic acid specificity targeting of active hepatic stellate cell and medicinal application thereof

A technology for targeting hepatic stellate cells and folic acid, which is applied to a polymer nanocarrier targeting activated hepatic stellate cells and its preparation and application fields, and can solve the coupling that has not yet specifically targeted hepatic stellate cells. Folic acid ligand polymer nanocarriers and other issues

Inactive Publication Date: 2016-05-11
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 nano-carrier for folic acid specificity targeting of active hepatic stellate cell and medicinal application thereof
  • Polymer nano-carrier for folic acid specificity targeting of active hepatic stellate cell and medicinal application thereof
  • Polymer nano-carrier for folic acid specificity targeting of active hepatic stellate cell and medicinal application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Isolation and Culture of Primary Rat Hepatic Stellate Cells (HSC)

[0028] 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

[0030] Culture of Activated Rat Hepatic Stellate Cells (HSC-T6)

[0031] 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

[0033] Analysis of mRNA expression changes of primary rat hepatic stellate cells (HSC) from resting state to activated state αSMA, Collagen1a1, FR-α

[0034] 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 nano-carrier for folic acid specificity targeting of an active hepatic stellate cell and medicinal application thereof. In the transformation process from a resting state to a muscle fibrosis sample active state, expression of an alpha type folate receptor in the hepatic stellate cell is remarkably enhanced. A folic acid-coupled polymer nano-micelle carrier is further prepared, and specificity targeting on the active primary rat hepatic stellate cell and cell strains of the polymer nano-micelle carrier is successfully achieved. According to a medicine nano-carrier system, polyethylene glycol is adopted as a material of a hydrophilic section, and resisting to protein adsorption and cell adhesion in blood circulation of the medicine nano-carrier system is ensured; polycaprolactone serves as a material of a hydrophobic section for nucleation, and loading of a plurality of hydrophobic anti-fibrosis medicines and fluorescent dye is facilitated. Folic acid coupled to a PEG shell guarantees that the carrier system conducts specificity recognition on folate receptors on the surface of the active hepatic stellate cell, finally, the utilization rate of the medicine is effectively increased, and the toxic and side effect of the medicine is lowered.

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