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EPI (epirubicin) SPION (superparamagnetic iron oxide nanoparticle) and preparation method thereof

A technology of iron oxide nanoparticles and epirubicin, which can be used in pharmaceutical formulations, organic active ingredients, medical preparations of non-active ingredients, etc., can solve problems such as toxic and side effects, and achieve easy acquisition, simple and cheap raw materials, and stable structure. Effect

Active Publication Date: 2013-07-03
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In the actual treatment process, although epirubicin has strong lethality to tumor cells, it is a non-specific antitumor drug for the cell cycle, and it also has greater lethality to normal cells. Severe toxic and side effects are inevitable, so finding a stable drug-loading method for epirubicin so that the drug only acts on the tumor site remains to be further studied

Method used

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  • EPI (epirubicin) SPION (superparamagnetic iron oxide nanoparticle) and preparation method thereof
  • EPI (epirubicin) SPION (superparamagnetic iron oxide nanoparticle) and preparation method thereof
  • EPI (epirubicin) SPION (superparamagnetic iron oxide nanoparticle) and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0036] Embodiment 1: Epirubicin superparamagnetic iron oxide nanoparticles and preparation method thereof

[0037] Epirubicin superparamagnetic iron oxide nanoparticles (EPI-SPION) are prepared from raw materials with the following weight ratio:

[0038] Ferric chloride (FeCl 2 4H 2 O): 10mg;

[0039] Ferric chloride (FeCl 3 ·6H 2 O): 27mg;

[0040] Sodium metasilicate (Na 2 SiO 3 9H 2 O): 28 mg;

[0041] Carbodiimide: 5mg;

[0042] 1-Ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl): 2mg;

[0043] Nitrogen hydroxysuccinimide (NHS): 2mg;

[0044] Epirubicin (EPI): 26mg;

[0045] The preparation method of above-mentioned EPI-SPION comprises the following steps successively:

[0046] (1) Weigh 10mg of ferric dichloride (FeCl2 4H2O), 27mg of ferric chloride (FeCl3 6H2O) and 28mg of sodium metasilicate (Na2SiO3 9H2O) in 500ml of purified water according to the above weight ratio, and use Dilute hydrochloric acid to adjust the pH to 1.5-2.0 and transfe...

Embodiment 2

[0050] Example 2: Determination of the Morphology and Particle Size of Epirubicin Superparamagnetic Iron Oxide Nanoparticles

[0051] Use a 200-mesh copper mesh support film dedicated to transmission electron microscopy to dip an appropriate amount of the Epi-SPION suspension prepared in Example 1, dry it at room temperature, and observe the size and shape of the nanoparticles under a JEM-1200EX transmission electron microscope. For the results, see figure 1 : The particle size of Epi-SPION nanoparticles is 8-10nm, the particles are regular, approximately spherical, the dispersion is good, and no obvious agglomeration occurs; take another appropriate amount (about 0.5ml) of nanoparticle suspension, and ultrasonically After dispersion treatment, dilute to 3-5 times, and use Zetasizer Nano S90 high-sensitivity nanometer particle size analyzer to measure the particle size and Zeta potential of nanoparticles. For the measurement results, see figure 2 : The particle size of EPI-SP...

Embodiment 3

[0052] Example 3: Determination of Magnetic Properties of Epirubicin Superparamagnetic Iron Oxide Nanoparticles

[0053] Get an appropriate amount of Epi-SPION suspension (about 1ml) prepared in Example 1, adopt the Lake Shore 7303 type vibrating sample magnetometer to test the magnetic properties of SPION magnetic nanoparticles, calculate its saturation magnetization, and the measurement temperature is 300K, The external magnetic field ranges from ?5000 to 5000 kA m -1 , record the change of hysteresis, and the strength H of the applied magnetic field (unit: kA m -1 ) is the abscissa, and the mass magnetization (unit: emu g -1 ) is the ordinate, draw the corresponding hysteresis loop, see the result image 3 : The hysteresis loops of Epi-SPION and SPION both pass through the origin and are center-symmetric to the origin, which proves that the coercive force of Epi-SPION and SPION is almost zero and has good superparamagnetism. The ungrafted drug SPION and The grafted epiru...

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Abstract

The invention provides an EPI SPION, which comprises ferrous chloride, ferric trichloride, sodium metasilicate, carbodiimide, EDC.HCI, N-hydroxyl succinimide and EPI. Fe<3+>, Fe<2+>, SiO3<2-> are taken as main raw materials, and the SPION is prepared through a chemical coprecipitation method; hydroxide radicals which exist on the surface of the SPION have a silane reaction with a silane coupling agent, and an active group carbonyl group is introduced; and by the aid of a nucleophilic reaction between amido and the carbonyl group, the EPI is grafted to the nanoparticle, so that a target product EPI SPION is obtained. The EPI-SPION has good conductivity and magnetic permeability, and under the action of an applied magnetic field, the nanoparticle can reach a tumor diseased region, normal tissue cells are not damaged, and an application value of targeted treatment for tumors is achieved.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to an epirubicin superparamagnetic iron oxide nanoparticle and a preparation method thereof. Background technique [0002] Cancer is one of the number one killers that seriously endanger human health. According to the statistics of the World Health Organization, there are 10 million cancer patients in the world every year, and about 6 million people die from cancer, accounting for 12% of the global death toll; There were 1.8 million cancer patients and 1.4 million deaths, an average of 1.3 people died of cancer every 3 minutes, and the incidence of cancer showed a sharp upward trend. Chemotherapy is one of the important methods to treat cancer. Epirubicin is a broad-spectrum anti-tumor chemotherapy drug commonly used in clinic. It is a derivative of doxorubicin, and it can quickly penetrate into tumor tissues and tumor cells DNA binding, inhibition of nucleic acid synthesis and mitosis, stron...

Claims

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Application Information

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IPC IPC(8): A61K9/14A61K41/00A61K31/704A61K47/04A61P35/00
Inventor 卢晓阳饶跃峰洪东升
Owner ZHEJIANG UNIV
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