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Tumor active-targeting nano drug delivery system capable of reversing drug-resistance

A nano-drug delivery system and active targeting technology, which can be used in anti-tumor drugs, drug combinations, anti-infective drugs, etc., and can solve the problems of low drug loading, capture, and poor hydrophilicity

Inactive Publication Date: 2015-03-11
FOURTH MILITARY MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

PLGA can wrap small molecule chemotherapy drugs, genes, proteins, etc. to form nanoparticles, but PLGA nanoparticles have low drug loading, poor hydrophilicity, are easily cleared by the immune system in blood circulation, and are easily captured by lysosomes when entering cells , reducing the delivery efficiency and efficacy of the drug

Method used

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  • Tumor active-targeting nano drug delivery system capable of reversing drug-resistance
  • Tumor active-targeting nano drug delivery system capable of reversing drug-resistance
  • Tumor active-targeting nano drug delivery system capable of reversing drug-resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0021] Preparation and antitumor activity of doxorubicin tumor-targeted drug delivery system

[0022] 1 Objective: To evaluate the antitumor activity of DOX-loaded lipid-mixed PLGA nanoparticles.

[0023] 2 Research methods:

[0024] 2.1 Determination of encapsulation efficiency and drug loading

[0025] The nanoparticles were dissolved in DMSO to destroy the nanoparticle structure, and the encapsulation efficiency and drug loading were detected by HPLC-MS / MS.

[0026] Drug loading = (the amount of drug wrapped in the drug delivery system / weight of the drug delivery system) × 100%

[0027] Encapsulation efficiency = (actual drug loading / dosage) × 100%

[0028] 2.2 Evaluation of acid sensitivity characteristics

[0029] The lipid-mixed PLGA nanoparticles were weighed, and the Zeta potential of the lipid-mixed PLGA nanoparticles in different pH (pH 5.0, pH 6.5 and pH 7.4) media was analyzed by laser particle size analyzer.

[0030] 2.3 Cytotoxicity evaluation

[0031] Huma...

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Abstract

The invention provides a tumor active-targeting nano drug delivery system capable of reversing drug-resistance. The drug delivery system is polylactic-co-glycolic acid (PLGA) nanoparticles mixed with lipid, and the nanoparticle core is PLGA. Drug-loaded nanoparticles are prepared as follows: inserting AA-polyethylene glycol-cholesterol linkers and triphenylphosphine-cholesterol linkers in the surface of PLGA; encapsulating DOX into the PLGA nanoparticles mixed with lipid to obtain the drug-loaded nanoparticles. The drug delivery system has the acid sensitivity, which enables the drug delivery system to proactively recognize tumor cells and position and release DOX into the mitochondria and cell nuclei of tumor cells, thereby enhancing the anti-tumor activity, reversing the drug-resistance of the tumor and providing a new strategy for improving the efficacy of DOX.

Description

technical field [0001] The present invention relates to a prescription composition and application scheme of a tumor active targeting nano drug delivery system capable of reversing drug resistance of tumors. The drug delivery system is a novel lipid mixed polylactic acid-glycolic acid copolymer ( PLGA) nanoparticles. Background technique [0002] Tumor is a kind of disease that seriously threatens human health. Doxorubicin (DOX) is the first-line drug for tumor chemotherapy, with definite curative effect and low price, but its clinical application is limited by its toxic side effects on normal tissues and easy drug resistance. Therefore, taking doxorubicin as the research object, construct a new drug delivery system with both tumor targeting and acid-sensitivity properties, increase the content of doxorubicin in tumor tissues, reduce its distribution in normal tissues, and reverse drug resistance, and obtain A novel tumor-targeted drug delivery system with high efficiency ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K31/704A61P35/00A61P31/00
Inventor 周四元成颖宋彦峰宦梦蕾崔晗腾增辉刘道洲刘苗叶威良张邦乐
Owner FOURTH MILITARY MEDICAL UNIVERSITY
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