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Novel diagnosis and treatment integrated hybridization micelle and preparation method thereof

A kind of micelle and hybrid technology, which is applied in the field of new hybrid micelle and its preparation for the integration of diagnosis and treatment, which can solve the problems of inability to effectively and clearly track and observe the therapeutic effect of drugs, the inability to organically combine cancer diagnosis and treatment, and low drug loading rate. problems, to achieve the effect of flexible and easy-to-control regulation, superior performance, and good biocompatibility

Inactive Publication Date: 2015-01-14
TONGJI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to provide a novel hybrid micelle for diagnosis and treatment and its preparation method in order to overcome the above-mentioned defects in the prior art. The drug rate is low, the drug leaks, the cancer diagnosis and treatment cannot be organically combined, and the drug treatment effect cannot be effectively and clearly tracked, and it can prolong the half-life of the drug in the body, improve the distribution of the drug in the body, and reduce the elimination of the drug by the kidney or liver , to protect the drug from degradation

Method used

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  • Novel diagnosis and treatment integrated hybridization micelle and preparation method thereof
  • Novel diagnosis and treatment integrated hybridization micelle and preparation method thereof
  • Novel diagnosis and treatment integrated hybridization micelle and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0041] (1) Preparation of mPEG-COOH (Mn: 2000)

[0042] In 50 mL of anhydrous 1,4-dioxane solution, add 2 g, 1 mmol mPEG (Mn: 2000), and 0.25 g, 2.5 mmol succinic anhydride, and add 0.125 g, 1 mmol DMAP as a catalyst. The mixed solution was reacted at room temperature for 24 hours under the protection of nitrogen; after the reaction was completed, the reaction solvent was removed by rotary evaporation. Then the reactant was dissolved in a small amount of dichloromethane, extracted and purified three times in a saturated NaCl solution, and the organic phase was collected; the collected product was precipitated in ether, filtered, the solid phase precipitate was collected, repeated twice, and vacuum dried The latter white powdery solid is mPEG-COOH.

[0043] (2)mPEG-S-S-NH 2 preparation

[0044] Under the protection of nitrogen, 0.62mmol EDC·HCl and 0.23mmol NHS were added to 0.4g, 0.2mmol mPEG-COOH in methylene chloride solution, and the reaction was stirred for 5h; 0.15g, 1mmol des...

Embodiment 2

[0048] (1) Preparation of mPEG-COOH (Mn: 5000)

[0049] In 50 mL of anhydrous 1,4-dioxane solution, add 2 g, 0.4 mmol mPEG (Mn: 5000), and 0.1 g, 1 mmol succinic anhydride, and add 0.05 g, 0.4 mmol DMAP as a catalyst. The mixed solution was reacted at room temperature for 24 hours under the protection of nitrogen; after the reaction was completed, the reaction solvent was removed by rotary evaporation. Then the reactant was dissolved in a small amount of dichloromethane, extracted and purified three times in a saturated NaCl solution, and the organic phase was collected; the collected product was precipitated in ether, filtered, the solid phase precipitate was collected, repeated twice, and vacuum dried The latter white powdery solid is mPEG-COOH.

[0050] (2)mPEG-S-S-NH 2 preparation

[0051] Under the protection of nitrogen, 0.62mmol EDC·HCl and 0.23mmol NHS were added to the dichloromethane solution dissolved in 1g, 0.2mmol mPEG-COOH, and the reaction was stirred for 5h; 0.15g, ...

Embodiment 3

[0056] Self-assembly of polymer composite micelles

[0057] Take 30mg mPEG-SS-MTX (Mn: 2000) and 20mg Pal-AAAAHHHD in a sample bottle, add 10ml deionized water and ultrasonic for 2h to self-assemble to form polymer composite micelles, and dialyze with a dialysis bag with a cutoff of 1000 minutes for 24h. Change the water every 6h to remove uncomplexed micelles.

[0058] Preparation of drug-loaded magnetic composite micelles by co-precipitation method

[0059] Add the configured Fe into the composite micelle solution under the protection of nitrogen 3+ , Fe 2+ The iron salt solution with a molar ratio of 2:3 was stirred vigorously at room temperature for 0.5h, then heated to 80°C under vigorous stirring, and ammonia water was slowly added to react for 1h. The magnetic ball was prepared by coprecipitation.

[0060] The particle size of the resulting polymer composite micelle is as image 3 As shown, the transmission electron microscope image is as Figure 4 Shown.

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Abstract

The invention relates to a novel diagnosis and treatment integrated hybridization micelle and a preparation method thereof. The hybridization micelle is a compound micelle which is self-assembled of two segmented copolymers through a dewatering effect. During preparation, the central nucleus of the compound micelle self-assembled of the two segmented copolymers through the dewatering effect is composed of an amphiphilic polymer hydrophobic chain segment and a hydrophobic medicine, a shell layer is a polymer hydrophilic chain segment, and special groups on the chain segment are used for generating magnetic nanoparticles on the shell layer in situ by a chemical coprecipitation method. Compared with the prior art, the preparation method has the advantages of being mild in preparation conditions and being simple, convenient and easy to carry out. The prepared micelle is stable in structure, has very good biocompatibility and biodegradability and can rapidly release medicine in a tumor environment, thus having the diagnosis-treatment integrated application potentiality.

Description

Technical field [0001] The invention belongs to the field of polymer nano biomedical materials, and particularly relates to a novel hybrid micelle with integrated diagnosis and treatment and a preparation method thereof. Background technique [0002] Cancer is a major disease endangering human health. Chemotherapy is the basic method of cancer treatment. Chemotherapy is of great significance for cancer treatment and the control of cancer cell metastasis. However, chemotherapy also faces many unsolved problems. For example, the drug has large side effects, low solubility, short circulation time, no targeting, and low drug utilization. The development of a new multifunctional nano-drug delivery system is the main way to solve such problems, so it has attracted extensive attention from many researchers. [0003] Polymer micelles are a common nano-drug delivery system. How to allow drugs to be selectively released at the diseased site while having multiple functions such as diagnosis ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K47/42A61K47/34A61K49/14A61K49/12
Inventor 李永勇马俊平董海青吴畏时东陆
Owner TONGJI UNIV
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