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Application of cell nucleus targeting chitosan-fatty acid graft as medicine carrier micelle

A technology of chitosan oligosaccharide and cell nucleus, which is applied in the application field of cell nucleus targeting chitosan oligosaccharide-fatty acid graft drug-loaded micelles, which can solve the problems of inability to achieve subcellular organelle targeting, and achieve the goal of improving anti-tumor efficacy and low toxicity Effect

Inactive Publication Date: 2009-11-25
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although microparticles and nanoparticles prepared with chitosan as the basic material have been widely used in the research of drug carrier materials, due to the hydrophilic structure of chitosan itself, it is difficult for it to be taken up by cells in large quantities, and sub- organelle targeting

Method used

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  • Application of cell nucleus targeting chitosan-fatty acid graft as medicine carrier micelle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] Example 1: Anti-tumor therapeutic application of chitosan-fatty acid graft drug-loaded micelles on lung cancer A549 cells

[0018] 1) Preparation of low molecular weight chitosan (chitooligosaccharide)

[0019] Get 90g of chitosan (92.5% degree of deacetylation) with a commercially available molecular weight of 450kDa, add it to 3000mL of 1.25% (v / v) hydrochloric acid aqueous solution, under the temperature condition of 55~60°C, after swelling for 2 hours, Add 5% cellulase (w / w), and degrade at a temperature of 55-60°C. Control the reaction temperature and time to obtain low molecular weight chitosan (chitooligosaccharide). The resulting degradation reaction solution was fractionated by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and the ultrafiltrate with a molecular weight of 10-50Kda was taken for freeze-drying. Gel permeation chromatography was used to measure the molecular weight of chitosan oligosaccharides, u...

Embodiment 2

[0035] Example 2: Anti-tumor therapeutic application of oligochitosan-stearic acid graft drug-loaded micelles on cervical cancer cell Hela cells

[0036] 1) Preparation of low molecular weight chitosan (chitooligosaccharide)

[0037] Get 90g of chitosan (92.5% degree of deacetylation) with a commercially available molecular weight of 450kDa, add it to 3000mL of 1.25% (v / v) hydrochloric acid aqueous solution, under the temperature condition of 55~60°C, after swelling for 2 hours, Add 5% cellulase (w / w), and degrade at a temperature of 55-60°C. Control the reaction temperature and time to obtain low molecular weight chitosan (chitooligosaccharide). The resulting degradation reaction solution was fractionated by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and the ultrafiltrate with a molecular weight of 10-50Kda was taken for freeze-drying. Gel permeation chromatography was used to measure the molecular weight of chitosan oli...

Embodiment 3

[0053] Example 3: Anti-tumor therapeutic application of chitosan oligosaccharide-fatty acid graft drug-loaded micelles with different degrees of amino substitution on lung cancer A549 cells

[0054] 1) Preparation of low molecular weight chitosan (chitooligosaccharide)

[0055]Get 90g of chitosan (92.5% degree of deacetylation) with a commercially available molecular weight of 450kDa, add it to 3000mL of 1.25% (v / v) hydrochloric acid aqueous solution, under the temperature condition of 55~60°C, after swelling for 2 hours, Add 5% cellulase (w / w), and degrade at a temperature of 55-60°C. Control the reaction temperature and time to obtain low molecular weight chitosan (chitooligosaccharide). The resulting degradation reaction solution was fractionated by ultrafiltration using 50Kda and 10Kda ultrafiltration membranes (Biomax-10, Millipore Co., USA), and the ultrafiltrate with a molecular weight of 10-50Kda was taken for freeze-drying. Gel permeation chromatography was used to ...

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Abstract

The present invention is application of medicine carrying chitosan-fatty acid grafting micelle in preparing targeting antitumor medicine carrier, especially antitumor medicine carrier targeting to lung cancer cell nucleus, cervical carcinoma cell nucleus and mammary cancer cell nucleus. The chitosan-fatty acid grafting micelle of the present invention has grafting carrier with low toxicity, and may be ingested fast by cell nucleus to target to cell nucleus and to raise the curative effect of antitumor medicine by up to 80 times. It has cell nucleus targeting function of permeating cell membrane fast with less destruction by intracellular lysosome. The grafting micelle with hydrophobic kernel can envelop hydrophobic antitumor medicine targeting cell nucleus to form medicine carrying grafting micelle. The present invention provides nanometer subcellular organelle administration for high efficiency low toxicity tumor treatment.

Description

technical field [0001] The invention belongs to the application of drug-loaded micelles of cell nucleus-targeted antitumor drugs, and relates to the application of drug-loaded micelles of cell nucleus-targeted chitosan-fatty acid grafts in the preparation of antitumor drugs. Background technique [0002] Tumor has always been a major disease that directly threatens human health. Due to the lack of molecular targeting of the drug itself, tumor chemotherapy has major treatment problems such as low cure rate and huge toxic side effects. Directly targeting drugs to diseased tissues (organs), cells and subcellular organelles through appropriate carrier technology is one of the important means to solve the low cure rate and toxic side effects of cancer chemotherapy. At present, scientists at home and abroad have made some progress in the tissue (organ) and cell targeting of anti-tumor drugs through nano-carrier technology, but they have not achieved breakthrough curative effects. ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/48A61K47/36A61P35/00A61K47/61
Inventor 胡富强杜永忠袁弘游剑
Owner ZHEJIANG UNIV
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