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Fe3O4 grafted copolymer heterozygote with multiple stimulus responses, and preparation method and application thereof

A multi-stimulus-response, hybrid technology, applied in the direction of drug combination, non-active ingredient medical preparations, and active ingredients-containing medical preparations, etc. To meet the complex environment of the cancerous site and other problems, to achieve excellent synergistic effect, good application value, and sensitive pH responsiveness.

Active Publication Date: 2018-02-23
SHAANXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is to overcome the lack of single responsiveness of existing block copolymer micelles, which cannot well meet the complex environment of cancerous parts in the human body, and fully and effectively utilize the lesion environment, thereby maximizing the use of drug carriers. Advantages to optimize drug release kinetics

Method used

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  • Fe3O4 grafted copolymer heterozygote with multiple stimulus responses, and preparation method and application thereof
  • Fe3O4 grafted copolymer heterozygote with multiple stimulus responses, and preparation method and application thereof
  • Fe3O4 grafted copolymer heterozygote with multiple stimulus responses, and preparation method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044]

[0045] 1. Preparation of Fe 3 o 4 Surface reversible addition-fragmentation chain transfer polymeric chain transfer agent

[0046] Prepare powdery magnetic Fe 3 o 4 Nanoparticles, and then according to the literature [Makhluf, S.B., etc. Small 4,1453–1458 (2008)] method on the powdery magnetic Fe 3 o 4 Nanoparticles undergo surface modification to introduce amino groups to give aminated Fe 3 o 4 Nanoparticles (amino group content is 18.25mmol·g -1 ). Aminated Fe 3 o 4 Nanoparticles (0.0105g, 0.1916mmol) were ultrasonically dispersed in 25mL of dry dichloromethane, CPADB (100mg, 0.3579mmol) and HOBT (0.0394g, 0.2915mmol) were dissolved in 25mL of dry dichloromethane, and the two The mixed solutions were transferred to a 150 mL three-necked flask, and mechanically stirred at 1000 rpm for 20 min under nitrogen protection. Next, EDC·HCl (0.1608g, 0.8388mmol) was dissolved in 10mL of dry dichloromethane, and added dropwise to the above mixed solution, kept un...

Embodiment 2

[0052]

[0053] In step 3 of Example 1, the Fe 3 o 4 -g-PAA 68 (0.04039g, 2.02×10 -5 mol) was fully dissolved in 2mL deionized water, and MAEFC (0.6896g, 2mmol), AIBN (0.0008g, 4.87×10 -3 mmol), other steps are identical with embodiment 1, obtain powdery Fe 3 o 4 -g-PAA-b-PMAEFC, yield 85%. The number-average molecular weights measured by NMR estimation and gel permeation chromatography are 30560 and 37120 respectively, recorded as Fe 3 o 4 -g-PAA 68 -b-PMAEFC 75 or P 1 .

Embodiment 3

[0055]

[0056] In step 2 of Example 1, the Fe 3 o 4 @CPADB (0.0262g, 0.192mmol), AA (1.972 mL, 28.7436mmol), AIBN (0.0078g, 0.0479mmol) were dissolved in a 50mL Shrek bottle filled with 8mL of 1,4-dioxane, other steps were the same as Embodiment 1 is identical, makes solid powdery Fe 3 o 4 -g-PAA, the yield is 86%, the number average molecular weight measured by NMR estimation and gel permeation chromatography is 9360 and 21620 respectively, recorded as Fe 3 o 4 -g-PAA 130 . Then, according to the method of embodiment 1 step 3, the Fe 3 o 4 -g-PAA 130 (0.04039 g, 2.02×10 -5 mol) was fully dissolved in 2mL deionized water, and MAEFC (0.6896g, 2mmol), AIBN (0.0008g, 4.87×10 -3 mmol), other steps are the same as in Example 1 to obtain Fe 3 o 4 -g-PAA-b-PMAEFC, yield 86%. The number-average molecular weight measured by NMR estimation and gel permeation chromatography is 36840 and 44700 respectively, recorded as Fe 3 o 4 -g-PAA 130 -b-PMAEFC 80 or P 4 .

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Abstract

The invention discloses a Fe3O4 grafted copolymer heterozygote with multiple stimulus responses, and a preparation method and an application thereof. The heterozygote provided by the invention is composed of magnet-responsive Fe3O4, pH-sensitive polyacrylic acid, and redox-sensitive polymethacrylate ferrocenylformyloxyethyl ester. The preparation method comprises the following preparation process:introducing a Fe3O4 surface chain transfer agent, and grafting polyacrylic acid and polymethacrylate ferrocenylformyloxyethyl ester onto the surface of Fe3O4 through two continuous steps of reversible addition-fragmentation chain transfer polymerization so as to obtain a Fe3O4 grafted acrylic acid-methacrylate ferrocenylformyloxyethyl ester segmented copolymer heterozygote. The heterozygote provided by the invention can be self-assembled into a spherical core-shell micelle in water, shows stimulus responsiveness to magnet, pH and redox, has the characteristic of releasing multiple stimulus responses to an anti-cancer drug namely paclitaxel, and can be used as a carrier of a hydrophobic drug and applied to targeted therapy of cancer.

Description

technical field [0001] The invention belongs to the technical field of biomedical polymer materials, and in particular relates to a multiple-stimuli-responsive Fe 3 o 4 Grafted acrylic acid-ferroceneformyloxyethyl methacrylate block copolymer hybrid, its preparation method and application in drug controlled release. Background technique [0002] Stimuli-responsive drug delivery systems (DDS) are a class of functional nano-drug delivery systems. As carriers for drug release, stimuli-responsive block copolymer micelles have attracted extensive attention due to their unique properties and wide range of applications in biomedical nanotechnology. This drug release carrier can be stimulated by some special biological environments in vivo / in vitro to change the structure, conformation and configuration of the carrier, or be subjected to physical or chemical factors such as light, temperature, pH, ultrasound, mechanical stress, reduction / oxidation, enzymes, Drugs are rapidly deli...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08F293/00C08F292/00C08F220/06C08F230/04A61K31/337A61K47/32A61K47/02A61K9/107A61P35/00
CPCA61K9/1075A61K31/337A61K47/02A61K47/32C08F230/04C08F292/00C08F293/00C08F2438/03C08F220/06
Inventor 罗延龄王园张雪银徐峰陈亚芍
Owner SHAANXI NORMAL UNIV
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