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Targeted lipid-silica complex carrying doxorubicin and its preparation and application

A technology for carrying doxorubicin and silicon dioxide, which is used in liposome delivery, preparations for in vivo tests, and medical preparations with inactive ingredients, etc. Oxidation and other problems, to achieve the effect of easy industrialization, low cost, and enhanced stability

Active Publication Date: 2017-07-18
SHANGHAI NAT ENG RES CENT FORNANOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The technical problem solved by the present invention is the weak stability of targeted liposome carrier and the problem of easy oxidation

Method used

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  • Targeted lipid-silica complex carrying doxorubicin and its preparation and application
  • Targeted lipid-silica complex carrying doxorubicin and its preparation and application
  • Targeted lipid-silica complex carrying doxorubicin and its preparation and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] (1) SiO 2 Embedding doxorubicin: Mix cyclohexane 5.5g, triton TX100 2g and n-hexanol 1.6g evenly, add 100μL 10mg / mL sodium fluoride solution to the mixed solution as the dispersed phase, and stir evenly Then form a reverse microemulsion; add 80 μL 0.05mol / L doxorubicin solution and 100 μL tetraethyl orthosilicate to the reverse microemulsion, and react for 24 hours to obtain a DOX-SiNP microemulsion system;

[0034] (2) Modified SiO with functional groups 2 : Use the method of synchronous modification of functionalized groups in the inverse microemulsion system to modify the amino group on the surface of the DOX-SiNP prepared above, that is, add 20 μL of APTES to the DOX-SiNP microemulsion system after the above reaction for 24 hours, and stir at room temperature After continuing to react for 24h, add ethanol to break the emulsion, centrifuge to collect the nanoparticles therein, and wash the collected nanoparticles with ethanol and water successively, cool and dry to ...

Embodiment 2

[0036] SiO in embodiment 1 2 @Dox is configured as a 10mg / ml ethanol dispersion, and FITC-APTES is configured as a 0.1mg / ml ethanol solution, and the above solutions are mixed in equal proportions, and after 4 hours of reaction, centrifuge to remove free FITC-APTES, which can be modified with FITC-APTES SiO 2 @Dox surface for confocal imaging and flow cytometry.

Embodiment 3

[0038] A kind of SiO that embodiment 1 makes 2 @Dox nanoparticles complexed with ordinary long-circulating liposomes. The specific steps are: the SiO prepared in Example 1 2@Dox Centrifuge and wash once with ultra-clean water, and configure it into a 2mg / ml ultra-pure water dispersion; dissolve mPEG-DSPE in chloroform, remove the solvent by rotary evaporation, add ultra-pure aqueous solution to the lipid film, ultrasonically disperse and Rotate and oscillate at 60 degrees in a water bath to obtain a liposome suspension; extrude through a carbonate membrane with a pore size of 50 nm to obtain liposomes with uniform particle size, and configure it into an ultrapure water dispersion of 0.2 mg / ml; Take 1ml of each of the above solutions, mix them in equal proportions of 1:1, and let them stand still for 24 hours; use 12000rpm to centrifuge to remove the solution layer, freeze-dry the precipitate layer, and obtain the SiO compound long-circulation liposome 2 @Dox nanoparticles (m...

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PUM

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Abstract

The present invention relates to a method for preparing a targeted lipid / silicon dioxide complex carrying doxorubicin. Firstly, silicon dioxide particles embed doxorubicin drug; then preparation of targeted liposome; finally, the above The two solutions were mixed, and the ratio of lipid to silicon dioxide was 1:10. After vortex shaking for 5 minutes, it was left standing still for 24 hours. After centrifugation at 12000rpm, the upper free lipid layer was removed, and the precipitated part was freeze-dried to obtain Targeted Lipid / SiO 2 Complex. The invention provides a coating method with targeting effect, good stability, high biocompatibility, long sustained release time, large drug loading capacity and high drug coating efficiency.

Description

technical field [0001] The invention relates to the preparation and application of composite medical materials, relates to a drug-embedded granular material, and is a cross application of liposome technology and inorganic particle carrier technology. Background technique [0002] As a drug carrier, liposome has the ability to enter the body and be swallowed by the reticuloendothelial system to activate the body's autoimmune function, change the distribution of the encapsulated drug in the body, and make the drug accumulate in tissues and organs such as liver, spleen, lung, and bone marrow, thereby Improve the therapeutic index of drugs, reduce the dosage of drugs and reduce the toxicity of drugs. However, the liposome system is a thermodynamically unstable system composed of phospholipids, cholesterol, etc., and its weak stability limits its use and affects its application as a drug carrier. During the storage of liposomes, phospholipids are prone to oxidative hydrolysis, t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/127A61K47/04A61K47/24A61K47/42A61K47/18A61K31/704A61K49/00A61P35/00
Inventor 何丹农严一楠王萍夏智伟颜娟金彩虹
Owner SHANGHAI NAT ENG RES CENT FORNANOTECH
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