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APARPAR polypeptide-modified invisible liposome and drug delivery system

A stealth liposome and polypeptide modification technology, which is applied in the direction of liposome delivery, antineoplastic drugs, drug combination, etc., can solve the problem of no expression and achieve the effect of improving the killing effect

Inactive Publication Date: 2013-04-17
SHANGHAI JIAO TONG UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that NRP-1 is highly expressed on the surface of glioma cells, but not in corresponding normal tissue epithelial cells
There is no report on the use of APARPAR peptide-mediated nano-drug delivery system for tumor-targeted therapy

Method used

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  • APARPAR polypeptide-modified invisible liposome and drug delivery system
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Embodiment 1, Preparation and Characterization of APARPAR-Liposome / DOX

[0023] The composition of the liposome membrane material formulation is HSPC (hydrogenated soybean lecithin) / Chol (cholesterol) / PEG-DSPE (polyethylene glycol-distearoylphosphatidylethanolamine complex) (14:6:2, mol / mol) , APARPAR modified PEG liposome membrane material formulation is HSPC / Chol / mPEG-DSPE / APARPAR-PEG-DSPE (14:6:2:1, mol / mol).

[0024] Each component was dissolved in chloroform, the solvent was removed by rotary evaporation, and the concentration of 0.1M (NH 4 ) 2 SO 4 Put the solution into the lipid film, ultrasonically disperse and rotate and shake in a water bath at 40°C to obtain a blank liposome suspension; then extrude through a carbonate film with a pore size of 50nm to obtain a blank liposome; Physiological saline is used as the mobile phase to pass through the Sephadex column, and the liposome part is collected, mixed with an appropriate amount of doxorubicin solution, l...

Embodiment 2

[0025] Embodiment 2, Preparation and Characterization of APARPAR-Liposome / DOX

[0026] The composition of the liposome membrane material formulation is HSPC (hydrogenated soybean lecithin) / Chol (cholesterol) / PEG-DSPE (polyethylene glycol-distearoylphosphatidylethanolamine complex) (16:6:4, mol / mol) , APARPAR modified PEG liposome membrane material formulation is HSPC / Chol / mPEG-DSPE / APARPAR-PEG-DSPE (16:6:4:1, mol / mol).

[0027] Each component was dissolved in methanol, the solvent was removed by rotary evaporation, and the concentration of 0.5M (NH 4 ) 2 SO 4 Put the solution into the lipid film, ultrasonically disperse and rotate and shake in a water bath at 70°C to obtain a blank liposome suspension; then extrude through a carbonate film with a pore size of 50nm to obtain a blank liposome; Physiological saline is used as the mobile phase to pass through the dextran gel column, the liposome part is collected, mixed with an appropriate amount of doxorubicin solution, left...

Embodiment 3

[0028] Embodiment 3, Preparation and Characterization of APARPAR-Liposome / DOX

[0029] The composition of the liposome membrane material formulation is HSPC (hydrogenated soybean lecithin) / Chol (cholesterol) / PEG-DSPE (polyethylene glycol-distearoylphosphatidylethanolamine complex) (14:6:2, mol / mol) , APARPAR modified PEG liposome membrane material formulation is HSPC / Chol / mPEG-DSPE / APARPAR-PEG-DSPE (14:6:2:1, mol / mol).

[0030] Each component was dissolved in chloroform, the solvent was removed by rotary evaporation, and a concentration of 0.3M (NH 4 ) 2 SO 4 Put the solution into the lipid film, ultrasonically disperse and rotate and shake in a water bath at 50°C to obtain a blank liposome suspension; then extrude through a carbonate film with a pore size of 50nm to obtain a blank liposome; Physiological saline is used as the mobile phase to pass through the dextran gel column, and the liposome part is collected, mixed with an appropriate amount of doxorubicin solution, ...

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Abstract

The invention discloses an APARPAR polypeptide-modified invisible liposome and a drug delivery system. The APARPAR polypeptide is modified on the surface of an invisible liposome. The membrane of the invisible liposome contains hydrogenated soybean lecithin, cholesterol, polyethylene glycol-stearoyl phosphatidyl ethanolamine and tearoyl phosphatidyl ethanolamine-polyethylene glycol-APARPAR. The invention further relates to the drug delivery system. The drug delivery system is formed by encapsulating an anti-tumor drug encapsulated with the APARPAR polypeptide-modified invisible liposome. The liposome drug delivery system can be used for targeted therapy of glioma and can go through the walls of blood vessels in a tumor mass under the mediating action of the APARPAR polypeptide to penetrate the inside of the whole tumor mass, so that the effect of killing the tumor cells is greatly improved.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to a stealth liposome modified by APARPAR polypeptide and a drug delivery system. Background technique [0002] Primary brain tumors have become one of the top ten causes of cancer death, with 5 to 10 malignant gliomas in every 100,000 people. According to the WHO grading system for glioma, the diagnosis of grade 4 glioma is the most difficult, and the average survival time of patients is only 12 months. Overall, few patients survived more than 3 years. Invasive glioma cells can rapidly infiltrate and destroy normal brain tissue structures, making it difficult to completely remove the tumor by surgery. Even with combined treatment of surgical resection, radiotherapy and chemotherapy, the average survival time of patients with malignant glioma is not more than one year. The main reason for the failure of chemotherapy is that anticancer drugs have no selectivi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/127A61K47/42A61K45/00A61K31/704A61P35/00A61K47/66A61K47/69
Inventor 杨一祎闫志强魏岱旭钟建金彩虹余震何丹农
Owner SHANGHAI JIAO TONG UNIV
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