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Magnetic nanoparticles with novel nuclear shell structure and pH responsibility as well as application thereof

A nanoparticle and composite nanoparticle technology, which is applied in the field of magnetic nanoparticles with novel core-shell structure and pH responsiveness and its application, and can solve the problem of no drug loading in composite nanoparticles

Inactive Publication Date: 2010-02-17
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Diblock copolymers of polyethylene glycol and polyacrylic acid monoglyceride or polymethacrylic monoglyceride encapsulated Fe 3 o 4 Composite nanoparticles of nanoparticles, the polyethylene glycol is on the surface of composite nanoparticles (reference: Shourong Wan, Yuee Zheng, Yuanqin Liu, Husheng Yan and Keliang Liu, J.Mater.Chem., 2005, 15, 3424 3430), Should have good biocompatibility, but the composite nanoparticles do not have drug-loaded functional groups

Method used

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  • Magnetic nanoparticles with novel nuclear shell structure and pH responsibility as well as application thereof
  • Magnetic nanoparticles with novel nuclear shell structure and pH responsibility as well as application thereof
  • Magnetic nanoparticles with novel nuclear shell structure and pH responsibility as well as application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0022] Preparation of MPEG-Br: Dissolve 10 g of dry MPEG (average molecular weight 2000) and 1.4 mL of triethylamine in 70 mL of tetrahydrofuran, slowly add 4.3 mL of α-bromoisobutyryl bromide and 20 mL of tetrahydrofuran dropwise under ice-water bath cooling and stirring The mixed solution, after the dropwise addition, was stirred and reacted at room temperature for 48 hours. The tetrahydrofuran was removed by rotary evaporation, and 100 mL of water was added to dissolve the resulting product. Then it was extracted with dichloromethane, 30 mL each time, for a total of 5 extractions, and the organic phase was collected. Wash with 1mol / L HCl (30mL×3), 1mol / L NaOH (30mL×3), saturated brine (30mL×3) successively, collect the organic phase, and finally wash with anhydrous MgSO 4 dry. Filter to remove the desiccant, and remove the solvent by rotary evaporation. The obtained concentrated solution is precipitated with ice anhydrous ether, and the precipitate is collected and vacuum...

Embodiment 2

[0024] The average molecular weight is 2000 MPEG in Example 1 is replaced by each 10g of dry MPEG with average molecular weight of 600, 1000, 5000 and 10000 respectively, except that the amount of α-bromoisobutyryl bromide used is different, other operations are the same as in Example 1. The amounts of α-bromoisobutyryl bromide used were: 14.3 mL, 8.6 mL, 3 mL and 2 mL, respectively. MPEG-Br of corresponding molecular weight was prepared.

Embodiment 3

[0026] Preparation of MPEG-b-PtBMA: 2g of MPEG-Br prepared in Example 1, 150mgCuBr, and 2.8g of tBMA were dissolved in 2.5mL of cyclohexanone, and 210 μL of PMDETA was added to the system under nitrogen protection and stirring, and the solution became shallow Green, continue to react for 2 hours, remove the reaction bottle, immerse in an oil bath preheated to 60°C, stir and react for 10 hours to obtain a green viscous substance. The resulting green polymer was dissolved in acetone to obtain a dark green solution, and the solution was passed through Al 2 o 3 Column, collect the filtrate, concentrate by rotary evaporation, and precipitate it with a mixture of water and methanol (4:1, volume ratio) to obtain a milky white floc. Vacuum drying for 24 hours can prepare MPEG-b-PtBMA. through 1 H NMR peak area integration, with MPEG as a reference, the degree of polymerization of PtMBA is 18.

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Abstract

The invention relates to magnetic composite nanoparticles with a multilayer nuclear-shell structure and Fe3O4 nanoparticles being wrapped by triblock copolymer as well as the application of the magnetic nanoparticles which are taken as drug carriers. A first block of the triblock copolymer is methoxyl polyethylene glycol, a second block of the triblock copolymer is random copolymer of crylic acidand acrylic ester, or random copolymer of methacrylic acid and methacrylic acid ester; and a third block of the triblock copolymer is polyacrylic acid monoglyceride or polymethylacrylic acid monoglyceride, wherein the third-block polymer is combined with the surface of the Fe3O4 nanoparticles; drugs with amino groups or amido groups, such as amycin, can be loaded on a polyanion layer at the sub-outer layer of the composite nanoparticles; and the loaded drugs are not released under the neutral conditions and released when the pH value is below 5.5.

Description

technical field [0001] The purpose of the present invention is to provide a kind of magnetic, pH sensitive, the outermost layer is the good polyethylene glycol of biocompatibility, the second outer layer is the polyanion that hydrophobicity can be adjusted and core is Fe 3 o 4 Composite nanoparticle (nano carrier) with multilayer core-shell structure of nanoparticle, its preparation method and application of the composite nanoparticle as drug carrier. Background technique [0002] The polymer / magnetic nanoparticle composite material is a composite material formed by dispersing magnetic inorganic nanoparticles in a polymer matrix. Since this material combines the advantages of polymers and magnetic inorganic nanoparticles, and has both magnetic responsiveness and polymer functionality, it shows broad application prospects in the fields of medicine, biochemistry and industrial applications, including cell separation, Sorting, immunoassays, immobilized enzymes, catalyst separ...

Claims

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Application Information

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IPC IPC(8): C08L53/00C08K3/22C08J3/20H01F1/11A61K47/34A61K31/704A61K31/407A61K31/136A61P35/00A61K47/10A61K47/32
CPCH01F1/0063
Inventor 刘克良阎虎生郭淼阎宇
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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