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Preparation method of polyglutamic acid PGA-coated superparamagnetic iron oxide nanoparticle

A technology of iron oxide nanometer and polyglutamic acid, which is applied in the preparations and pharmaceutical formulations for in vivo experiments, can solve the problem of not finding SPIO nanoparticles, and achieve a remarkable contrast effect, good water solubility, and low raw material cost. Effect

Inactive Publication Date: 2015-04-29
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the above method mainly uses positively charged polyethyleneimine (PEI) as a stabilizer, which requires further functionalization before it can be used for cell or tumor MR imaging.
[0005] Searching the literature at home and abroad, there is no relevant report on the preparation of PGA-coated SPIO nanoparticles as MRI contrast agents by mild reduction method

Method used

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  • Preparation method of polyglutamic acid PGA-coated superparamagnetic iron oxide nanoparticle
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  • Preparation method of polyglutamic acid PGA-coated superparamagnetic iron oxide nanoparticle

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Experimental program
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Embodiment 1

[0062]Dissolve 640mg of ferric chloride hexahydrate in 50mL of ultrapure water, blow in nitrogen gas for 10 minutes and stir thoroughly. Dissolve 90 mg of PGA in 20 mL of ultrapure water, and add the above solution dropwise. After stirring evenly, add 9mg / mL sodium sulfite solution dropwise. Transfer the mixed solution to a 60°C water bath, add 1 mL of ammonia water, and fully react for 30 minutes. The mixed solution was moved to room temperature, and the reaction was continued for 1.5 hours. The prepared solution was centrifuged at a speed of 8000 rpm for 10 minutes, the centrifuged precipitate was discarded, and the upper layer solution was taken. Dialyze with a dialysis bag with a molecular weight cut off of 8000-14000. The dialysis water was distilled water, and the dialysis was carried out for three days, and the water was changed three times a day. The iron ferric oxide nanoparticles coated with polyglutamic acid prepared by the present invention are observed by tran...

Embodiment 2

[0064] The concentration of Fe element in the SPIO-PGA nanoparticle solution prepared by the present invention is determined by ICP-OES test method. Prepare 2 mL of SPIO-PGA nanoparticle aqueous solutions with Fe concentrations of 0.004, 0.008, 0.016, 0.032, and 0.064 mM, and measure the T of the material at different Fe concentrations by a magnetic resonance imaging analyzer. 2 relaxation effect (see attached Figure 5 ). The results of relaxation rate test show that the reciprocal of relaxation time of SPIO nanomaterials has a good linear relationship with the increase of iron concentration (within the concentration range of 0.004-0.064mM). The r of the SPIO-PGA prepared by the present invention can be obtained by calculation 2 Relaxation rate up to 333.7mM -1 the s -1 . Therefore, the SPIO-PGA prepared by the present invention can be used as an excellent T 2 Signal attenuating contrast agents.

Embodiment 3

[0066] HeLa cells were used as model cells to evaluate the effect of SPIO-PGA nanoparticles prepared by the present invention on cell viability. Bare Fe prepared in Comparative Example 1 3 o 4 Nanoparticles served as controls. The solution obtained in Example 1 was sequentially prepared into physiological saline solutions (sodium chloride content 0.9%) with Fe element concentrations of 50, 150, 250, 350, 450 μg / mL SPIO-PGA nanoparticles. HeLa cells were planted in a 96-well plate, and 5 parallel samples were set for each concentration, and the cell culture plate was placed in CO 2 The concentration was 5% and the temperature was 37° C. for 24 hours. After MTT treatment, the absorbance value of each well at λ=570nm was detected on a microplate reader, and the corresponding cell viability was calculated accordingly. The cells treated with normal saline were used as the blank control, and the cell viability was recorded as 100%. compared with control exposed Fe 3 o 4 In con...

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Abstract

The invention relates to a preparation method of a polyglutamic acid PGA-coated superparamagnetic iron oxide nanoparticle. The preparation method comprises the following steps: dissolving trivalent ferric salt in water, stirring and filling nitrogen; adding a polyglutamic acid PGA solution dropwise, and then adding a sodium sulfite Na2SO3 aqueous solution dropwise while stirring so as to obtain mixed solution; then, transferring the mixed solution to a water bath, dropping NH3.H2O while stirring and reacting for 20-30min; and reacting at room temperature for 0.5-1.5hr, centrifuging and dialyzing so as to obtain the nanoparticle. The preparation method disclosed by the invention is quite simple in process, moderate in reaction condition, easy to operate, safe and free from pollution; and the prepared SPIO-PGA nanoparticle is uniform in particle size distribution, relatively small in particle size, high in relaxation rate, significant in contrast effect, good in water solubility, colloidal stability, biocompatibility and blood compatibility, free from adverse influence on organism, low in cost and easy to preserve.

Description

technical field [0001] The invention belongs to the field of preparation of magnetic resonance contrast agents, in particular to a preparation method of polyglutamic acid PGA-coated superparamagnetic iron oxide nanoparticles. Background technique [0002] Magnetic resonance imaging (MRI) technology is a high-resolution imaging technology with high spatial and tomographic imaging capabilities. MRI has no ionization damage caused by radiation, and can obtain anatomical and physiological information at the same time. It has unparalleled advantages in other medical imaging. The advantages. Magnetic resonance imaging is playing an increasingly important role in the field of disease surveillance. However, the weakness of MRI is its low sensitivity, and the overlapping relaxation times of different organs or tumor tissues make MRI diagnosis difficult. In recent years, the problem of low MRI sensitivity can be effectively solved by injecting MRI contrast agent. Therefore, it is p...

Claims

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Application Information

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IPC IPC(8): A61K49/12
Inventor 史向阳于智博罗宇彭琛
Owner DONGHUA UNIV
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