Injectable temperature-sensitive magnetic nano emulsive gel and preparation method and application thereof

A magnetic nano-gel technology, applied in biological and medical nano-materials and fields, can solve the problems of dispersion, damage to normal tissues, affecting the treatment effect, etc., and achieve the effects of excellent heating performance, prolonging survival period and good appearance.

Active Publication Date: 2017-05-31
SOUTHEAST UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Intravenous injection is through the long circulation in the body, using the tumor-enhanced osmotic retention effect (EPR effect) to enrich in the tumor area, but the dose of nanoparticles reaching the tumor is very small, most of which are trapped by the liver and spleen, and some magnetic nanomaterials heat up Due to the lack of performance, it is usually necessary to apply a high-frequency magnetic field and multiple times of magnetic hyperthermia to obtain a certain effect, which reduces the effect of tumor hyperthermia and also damages normal tissues; intratumoral injection increases the content of nanoparticles in tumor tissues , the treatment effect can be improved, but the problem it brings is that the intratumoral pressure of the tumor tissue makes it easy for the injected magnetic nanoparticles to leak through the needle hole of the syringe, and it is easy to diffuse from the tumor tissue to the surrounding normal tissue, making the normal tissue in the treatment process The lack of image guidance during the operation also makes the injection position prone to deviation and affects the therapeutic effect

Method used

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  • Injectable temperature-sensitive magnetic nano emulsive gel and preparation method and application thereof
  • Injectable temperature-sensitive magnetic nano emulsive gel and preparation method and application thereof
  • Injectable temperature-sensitive magnetic nano emulsive gel and preparation method and application thereof

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preparation example Construction

[0029] The main steps of the preparation method of the injectable temperature-sensitive magnetic nanoemulsion gel of the present invention are: adding oil-soluble ZnFe 2 O 4 The nanoparticles are added to the silicone oil to fully disperse the nanoparticles, and the resulting mixture serves as the oil phase. The oil phase is added dropwise to boiling water dissolved with the surfactant sodium lauryl sulfate under stirring to obtain colostrum, and then ultrasonically emulsified with an ultrasonic cell disruptor to obtain a stable oil-in-water magnetic nanoemulsion. Then, the liquid PEG-DA (polyethylene glycol diacrylate) is added dropwise to the magnetic nanoemulsion under low temperature conditions, and the ultrasonic dispersion makes the PEG-DA molecules fully dispersed between the magnetic nanoemulsions to obtain the magnetic nanoemulsion. Emulsion gel, stored at 4 degrees low temperature.

[0030] Among them, ZnFe in the oil phase 2 O 4 The nano-particle size is between 10-20 ...

Embodiment 1

[0034] Preparation of ZnFe by high temperature thermal decomposition method 2 O 4 Nanoparticles

[0035] Add 2mmol of iron acetylacetonate, 1mmol of zinc acetylacetonate, 20mL of reaction solvent dibenzyl ether, and 12mmol of surfactants oleic acid and oleylamine in a 100ml three-necked flask with a beveled neck. Oxygen also plays a role of stirring, while condensing and refluxing. Heat the reaction system to a nucleation temperature of 220°C at a heating rate of 3.3°C / min through a programmed temperature control device, and keep the temperature for 1 hour. This stage is the nucleation stage of magnetic iron oxide nanoparticles. During the process, the solution turns from brownish red to red. Translucent black. Then, the reaction system was still heated to a growth temperature of 290°C at a heating rate of 3.3°C / min, and the reaction system was maintained at this temperature for 30 minutes to complete the reaction. After the reaction is over, remove the heat source. After the r...

Embodiment 2

[0038] Preparation of magnetic nanoemulsion gel

[0039] The oil-soluble ZnFe prepared in Example 1 2 O 4 Add 10 mg of the nano particles in terms of iron to 2 ml of silicone oil, and mix the nano particles and the silicone oil thoroughly with a vortex, and the resulting mixture is used as the oil phase. The oil phase was added dropwise to boiling water with 200 mM sodium lauryl sulfate dissolved in a stirring state at a rotational speed of 600 r / min, and stirring was continued for 30 minutes, and the volume was dilute to 4 ml with ultrapure water to obtain colostrum. A stable oil-in-water magnetic nanoemulsion was obtained by ultrasonic emulsification and dispersion for 30 minutes with an ultrasonic cell disruptor with a power of 300w. Then add 2ml of liquid PEG-DA dropwise to the magnetic nanoemulsion under low temperature conditions, and 100w power ultrasonic dispersion makes the PEG-DA molecules fully dispersed between the magnetic nanoemulsions to obtain the magnetic nanoemu...

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Abstract

The invention discloses a preparation method of an injectable temperature-sensitive magnetic nano emulsive gel. The preparation method comprises the following steps: by taking a mixture of silicone oil and ZnFe2O4 nanoparticles as an oil phase and an aqueous solution where lauryl sodium sulfate is dissolved as an aqueous phase, dropwise adding the oil phase into the boiling aqueous phase while stirring to form an initial emulsion; performing uniform nanocrystallization on the initial emulsion by using an ultrasonic cell crusher to obtain a magnetic nanoemulsion; dropwise adding polyethylene glycol diacrylate (PEG-DA) into the magnetic nanoemulsion under a low temperature condition, performing uniform ultrasonic dispersion, and fully cooling the mixture to obtain the magnetic nano emulsive gel which is good in flowability at normal temperature (less than 25 DEG C) and is gelatinized at body temperature (37 DEG C). The magnetic nano emulsive gel prepared by the invention can be injected in situ in a subcutaneous tumor of a mouse under guidance of an image and is gelatinized and fixed in the part of tumor, without leaking from an injection hole or diffusing to peripheral normal tissues and blood vessels; by applying an alternating magnetic field, the ZnFe2O4 nanoparticles generate heat to cause thermal ablation of tumor tissues for necrosis and exfoliation. The method has a wide application prospect in solid tumor interventional thermotherapy.

Description

Technical field [0001] The invention belongs to the biological and medical nanomaterials and technical fields, and specifically relates to a preparation method and application of an injectable temperature-sensitive magnetic nanoemulsion gel. Background technique [0002] Nanoemulsion is a thermodynamically stable system with a particle size of 10-100nm formed by water, oil, surfactant and co-surfactant in an appropriate proportion. The main types are water-in-oil, oil-in-water and bicontinuous . The emulsion droplets are mostly spherical, uniform in size, and transparent or slightly opalescent liquid in appearance. The main preparation methods of nanoemulsion include shear stirring method, high-pressure homogenizer homogenization method, ultrasonic method and phase change method, etc., which are easy to prepare, simple to operate, long-term storage without layering and demulsification, and can be filtered and sterilized. As a new type of drug carrier, nanoemulsion is small in s...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K9/107A61K49/08A61K49/18A61K49/22A61P35/00
CPCA61K9/0019A61K9/1075A61K41/0052A61K49/08A61K49/1806A61K49/226
Inventor 张宇武昊安马明顾宁
Owner SOUTHEAST UNIV
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