CN112591802A - Preparation method of hollow ferroferric oxide drug-loaded nanoparticles - Google Patents
Preparation method of hollow ferroferric oxide drug-loaded nanoparticles Download PDFInfo
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- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 239000003814 drug Substances 0.000 title claims abstract description 40
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 37
- 229940079593 drug Drugs 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims abstract description 43
- 229940009456 adriamycin Drugs 0.000 claims abstract description 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 238000011534 incubation Methods 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 9
- 229910001220 stainless steel Inorganic materials 0.000 claims description 7
- 239000010935 stainless steel Substances 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 6
- 238000003760 magnetic stirring Methods 0.000 claims description 6
- 230000010355 oscillation Effects 0.000 claims description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 claims description 5
- 239000005695 Ammonium acetate Substances 0.000 claims description 5
- 229940043376 ammonium acetate Drugs 0.000 claims description 5
- 235000019257 ammonium acetate Nutrition 0.000 claims description 5
- NQXWGWZJXJUMQB-UHFFFAOYSA-K iron trichloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].Cl[Fe+]Cl NQXWGWZJXJUMQB-UHFFFAOYSA-K 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 238000007605 air drying Methods 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000001027 hydrothermal synthesis Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- -1 polytetrafluoroethylene Polymers 0.000 claims description 3
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 3
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 abstract description 13
- 229910052742 iron Inorganic materials 0.000 abstract description 8
- 206010028980 Neoplasm Diseases 0.000 abstract description 4
- 238000004729 solvothermal method Methods 0.000 abstract description 4
- 238000002512 chemotherapy Methods 0.000 abstract description 2
- 230000005389 magnetism Effects 0.000 abstract description 2
- 230000008685 targeting Effects 0.000 abstract description 2
- 238000001514 detection method Methods 0.000 description 27
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 230000004580 weight loss Effects 0.000 description 9
- 239000012467 final product Substances 0.000 description 8
- 239000004005 microsphere Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 238000011068 loading method Methods 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 239000011148 porous material Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 102000016938 Catalase Human genes 0.000 description 5
- 108010053835 Catalase Proteins 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 238000001878 scanning electron micrograph Methods 0.000 description 5
- 238000010586 diagram Methods 0.000 description 4
- 239000000589 Siderophore Substances 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- 230000005415 magnetization Effects 0.000 description 3
- 238000004445 quantitative analysis Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000012798 spherical particle Substances 0.000 description 3
- 238000000026 X-ray photoelectron spectrum Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000000696 nitrogen adsorption--desorption isotherm Methods 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 208000024770 Thyroid neoplasm Diseases 0.000 description 1
- 230000004931 aggregating effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 238000000724 energy-dispersive X-ray spectrum Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229940044631 ferric chloride hexahydrate Drugs 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000002122 magnetic nanoparticle Substances 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 229910052596 spinel Inorganic materials 0.000 description 1
- 239000011029 spinel Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01G—COMPOUNDS CONTAINING METALS NOT COVERED BY SUBCLASSES C01D OR C01F
- C01G49/00—Compounds of iron
- C01G49/02—Oxides; Hydroxides
- C01G49/08—Ferroso-ferric oxide [Fe3O4]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5115—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Pharmacology & Pharmacy (AREA)
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- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- Engineering & Computer Science (AREA)
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Abstract
The invention discloses a preparation method of hollow ferroferric oxide drug-loaded nanoparticles, belonging to the technical field of medicines and comprising the following steps: (1) preparation of hollow ferroferric oxide nanoparticles, and (2) preparation of hollow ferroferric oxide drug-loaded nanoparticles. The invention synthesizes hollow ferroferric oxide nanoparticles based on a solvothermal method, loads adriamycin serving as a medicine, and realizes the active targeting capacity of the medicine of an external magnetic field and the tumor treatment of the cooperation of iron death and chemotherapy by using the good magnetism of the hollow ferroferric oxide nanoparticles.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a preparation method of hollow ferroferric oxide medicine-carrying nanoparticles.
Background
At present, the treatment method for tumors is limited, and the generated effect is also limited, so that the search for a new medicament, a method and the like with better effect is a problem which needs to be solved urgently by the technical personnel in the field.
Disclosure of Invention
The invention aims to provide a preparation method of hollow ferroferric oxide drug-loaded nanoparticles.
The technical purpose of the invention is realized by the following technical scheme:
a preparation method of hollow ferroferric oxide drug-loaded nanoparticles comprises the following steps:
(1) preparing hollow ferroferric oxide nanoparticles:
dissolving ferric trichloride hexahydrate in ethylene glycol, performing ultrasonic oscillation and magnetic stirring at room temperature until the ferric trichloride is dissolved, then adding ammonium acetate, performing further ultrasonic oscillation and magnetic stirring at room temperature for 30min until the ferric trichloride is completely dissolved, then transferring the solution to a stainless steel hydrothermal kettle, placing the stainless steel hydrothermal kettle in a forced air drying oven at 200 ℃ for hydrothermal reaction for 16.5h, cooling to room temperature after the reaction is finished, collecting the solution by using a magnet, respectively washing the solution by using absolute ethyl alcohol and deionized water for four times, dispersing the solution in water, and storing the solution at 4 ℃ for later use to obtain hollow ferroferric oxide nanoparticles;
(2) preparing hollow ferroferric oxide drug-loaded nanoparticles:
and (2) uniformly mixing the hollow ferroferric oxide nanoparticles prepared in the step (1) with adriamycin, placing the mixture in a shaking table for incubation, performing magnetic attraction on the mixture by using a magnet after the incubation is finished to remove free adriamycin, dispersing the mixture in deionized water, and storing the mixture at 4 ℃ for later use to obtain the hollow ferroferric oxide drug-loaded nanoparticles.
Further, the amount of ferric chloride hexahydrate used in step (1) was 1.350 g.
Further, the amount of ethylene glycol used in step (1) was 70 mL.
Further, the amount of ammonium acetate used in step (1) was 3.854 g.
Further, the stainless steel hot kettle in the step (1) is a polytetrafluoroethylene lining.
Further, the dosage of the hollow ferroferric oxide nanoparticles in the step (2) is 1mL, and the concentration is 10 mg/mL; the dosage of the adriamycin is 40 mu L, and the concentration is 25 mg/mL.
Further, the temperature in the shaking table is controlled to be 37 ℃ during the incubation in the step (2), the rotating speed is controlled to be 100rpm, and the incubation time is 2 hours.
Compared with the prior art, the invention has the following advantages:
the invention synthesizes hollow ferroferric oxide nanoparticles based on a solvothermal method, loads adriamycin serving as a medicine, realizes the active targeting capacity of the medicine of an external magnetic field by using the good magnetism of the hollow ferroferric oxide nanoparticles, realizes the tumor treatment of the cooperation of iron death and chemotherapy, and is probably applied to the treatment application of superficial tumors such as thyroid cancer and breast cancer in the future.
Drawings
FIG. 1 is a diagram showing a UV spectrum and a standard curve.
Fig. 2 is a graph showing the results of DLS detection.
Fig. 3 is an SEM image of hollow ferroferric oxide after loading with a drug.
FIG. 4 is an SEM image of the hollow ferroferric oxide after being loaded with drugs and dried.
FIG. 5 is an EDS spectrogram and a quantitative analysis result chart of hollow ferroferric oxide after drug loading.
Figure 6 is the XRD spectrum of the final product.
FIG. 7 shows the hysteresis loop of the final product measured at room temperature.
FIG. 8 is a graph showing the thermogravimetric analysis of the final product when heated from room temperature to 900 ℃.
Figure 9 is the XPS spectrum of the final product.
Fig. 10 is an N2 adsorption-desorption isotherm and a pore size distribution diagram of hollow ferroferric oxide.
FIG. 11 is a graph of the in vitro release profile of hollow siderophores.
FIG. 12 is a graph showing the change in the concentration of dissolved oxygen in hollow iron with time.
Detailed Description
Example 1
(1) Preparing hollow ferroferric oxide nanoparticles:
dissolving 1.350g of ferric trichloride hexahydrate in 70mL of ethylene glycol, performing ultrasonic oscillation at room temperature, performing magnetic stirring until the ferric trichloride is dissolved, then adding 3.854g of ammonium acetate into the solution, performing further ultrasonic oscillation at room temperature, performing magnetic stirring for 30min until the ferric trichloride is completely dissolved, transferring the solution into a stainless steel hot kettle with a 100mL of polytetrafluoroethylene lining, performing hydrothermal reaction for 16.5h in a forced air drying oven at 200 ℃, cooling to room temperature after the reaction is finished, collecting the solution with a magnet, respectively washing the solution with absolute ethyl alcohol and deionized water for four times, dispersing the solution in water, and storing the solution at 4 ℃ for later use to obtain hollow ferroferric oxide nanoparticles;
(2) preparing hollow ferroferric oxide drug-loaded nanoparticles:
uniformly mixing 10mg/mL and 1mL of hollow ferroferric oxide and 25mg/mL and 40 mu L of adriamycin, placing the mixture in a 37 ℃ shaking table, incubating the mixture for 2 hours at the rotating speed of 100rpm, magnetically absorbing the free adriamycin by using a magnet after the incubation is finished, dispersing the mixture in deionized water, and storing the mixture at 4 ℃ for later use to obtain the hollow ferroferric oxide drug-loaded nanoparticles.
The experimental reagents used in the above examples were:
the experimental apparatus used was:
the drug prepared in example 1 was characterized by the following assay.
The method comprises the following steps:
(1) drug loading rate detection
And (3) detection results:
1) measuring DOX concentration in the supernatant by ultraviolet to obtain ultraviolet spectrum and standard curve shown in FIG. 1;
2) concentration sample measurement data:
(2) and (3) DLS detection:
the detection results are shown in FIG. 2; a and B in FIG. 2 respectively show DLS detection results before and after hollow ferroferric oxide drug loading. As can be seen from the figure, the hydrodynamic size of the hollow ferroferric oxide is 486nm, the Zeta potential is-26.2 mV, and the hydrodynamic size and the Zeta potential after the drug adriamycin is loaded are 513nm and-24.0 mV respectively. Thus, changes in particle size and potential indicate successful loading of the drug.
(3) And (4) SEM detection:
the results of the detection are shown in FIGS. 3 and 4 below; fig. 3 shows an SEM image of the hollow ferroferric oxide loaded with the drug, and it can be seen that the product is a uniform spherical particle with uneven surface, obvious furrows, uniform size, and a particle size of about 450 nm. In fig. 4, an SEM image of the product dried in an oven at 60 ℃ for 4 hours is shown, and it is observed that some particles have openings on the surface, and further enlarged observation is made on the opened individual particles, as shown in the right image, it can be clearly seen that the spherical particles have an open-ended hollow structure.
(4) And (4) EDS detection:
the results of the detection are shown in FIG. 5; fig. 5 shows an EDS spectrum and a quantitative analysis result of the hollow ferroferric oxide loaded with drugs, and it can be seen that the measured sample contains only O and Fe elements, and the corresponding percentage is close to the element percentage in Fe3O 4.
(5) XRD detection:
the results of the detection are shown in FIG. 6; figure 6 shows the XRD spectrum of the final product. 9 obvious diffraction peaks appear in the figure, and the position and the relative intensity of each diffraction peak are equal to that of Fe3O4The XRD cone mapping patterns (JCPDS cards: 79-0419) are consistent, the corresponding diffraction crystal faces are respectively (111), (220), (311), (222), (400), (422), (511), (440) and (533), and no other miscellaneous peaks exist in the figure, which indicates that the obtained product is singleFerroferric oxide with a spinel structure.
(6) And VSM detection:
the results of the detection are shown in FIG. 7; FIG. 7 shows the hysteresis loop of the final product measured at room temperature. The magnetic induction of the magnetic microspheres increased with the increase of the applied magnetic field and gradually reached saturation after 2500(Oe), and the saturation magnetization thereof was 75.73 emu/g. After the external magnetic field is removed, the residual magnetization and the coercive force of the magnetic microsphere are 5.42emu/g and 50Oe respectively.
(7) TGA detection:
the detection results are shown in FIG. 8 below; FIG. 8 shows the thermogravimetric curve of the final product measured from room temperature to 900 ℃: including TGA (black line) and DTG (blue line). Wherein TGA shows the weight loss process of the sample and DTG shows the temperature corresponding to the maximum weight loss rate. The weight loss process of the sample is divided into three processes, when the temperature is increased to 217 ℃, 1% of mass loss occurs, and the temperature corresponding to the maximum weight loss rate is 272 ℃; a second weight loss process occurs when the temperature is continuously increased to 395 ℃, and the mass loss and the maximum weight loss rate temperature at the moment are respectively 3 percent and 427 ℃; when the temperature is continuously increased to 825 ℃, a third weight loss process occurs, the weight loss is stabilized when reaching about 12 percent, and the maximum weight loss rate temperature is 884 ℃. According to scanning electron microscope pictures and documents, the magnetic microspheres prepared by the solvothermal method are formed by aggregating smaller (15-30 nm) magnetic nanoparticles. It can therefore be concluded that 1% of the mass lost when the temperature rises to 217 ℃ is mainly due to evaporation of the water adsorbed on the surface; when the temperature is continuously increased to 395 ℃, a small amount of adriamycin adsorbed on the surface begins to degrade, so that the magnetic microspheres further lose weight; when the temperature is continuously increased to 825 ℃, the magnetic microspheres begin to collapse, the adriamycin in the magnetic microspheres starts to be rapidly degraded, and the mass loss of 12% occurs.
The result shows that the prepared magnetic microsphere has good thermal stability.
(8) XPS detection:
the detection results are shown in FIG. 9; figure 9 shows the XPS spectra of the final product, with the parameters obtained from the spectra listed in the table below. The Fe, O, C and N elements in the product can be identified according to the position of a characteristic spectral line appearing in a spectrogram, and the highest atomic content is Fe and O, the next is C and the lowest is N according to the parameters in a table according to the content of reaction atoms in photoelectron spectral line intensity (area of a photoelectron peak) in an energy spectrogram.
(9) And (3) BET detection:
the detection results are shown in fig. 10; FIG. 10 shows the N2 adsorption-desorption isotherm and the pore size distribution diagram of the hollow ferroferric oxide, and the measured corresponding parameters are shown in the diagram. It can be seen from the figure that the adsorption-desorption curve is not closed, the specific surface area and pore volume of the material are small, and it can be seen from the pore size distribution that the material is not adsorbed before 5nm, and an adsorption peak appears around 13nm, which may be due to adsorption caused by the voids between the nanoparticles. The results show that a small amount of pore structures exist in the hollow ferroferric oxide, and the drug molecules are mainly distributed in the cavity of the carrier.
(10) In vitro release detection:
and (3) detection results:
1) the in vitro release profile of hollow siderophore doxorubicin is shown in figure 11;
2) the in vitro release results of hollow siderophore doxorubicin were as follows:
as can be seen from the in vitro release curve of the adriamycin, the cumulative release amount of the adriamycin is gradually increased along with the prolonging of time, the release of the adriamycin is close to the balance after 12h, and the maximum release amount reaches 88.56%.
(11) Catalase Activity detection
The detection results are shown in fig. 12 below; FIG. 12 shows the evaluation of catalase activity of hollow iron by measuring the change of dissolved oxygen concentration with time using a dissolved oxygen measuring instrument. As can be seen from FIG. 12, the concentration of dissolved oxygen increased with time, and the catalase activity increased, reaching a maximum at 80 s. Then, as time passed, the dissolved oxygen concentration was reduced for a short time and thereafter reached a plateau, indicating that the catalase activity was saturated.
In conclusion, the invention synthesizes hollow ferroferric oxide nanoparticles based on a solvothermal method, and loads a drug adriamycin. The drug loading rate of doxorubicin was determined by uv. DLS and SEM show that the average particle size of the sample is 450nm, and SEM images of the dried product can clearly show that spherical particles are in an open-ended hollow structure. The elemental percentage and the crystalline structure in Fe3O4 were analyzed by EDS and XRD. The VSM can detect the residual magnetization intensity and the coercive force of the hollow ferroferric oxide. XPS enables quantitative analysis of the elemental content of the product. TGA detection results show that the prepared magnetic microspheres have good thermal stability. BET detection results show that a small amount of pore structures exist in the hollow ferroferric oxide, and drug molecules are mainly distributed in the cavity of the carrier. The in vitro release result shows that the maximum release amount of the adriamycin reaches 88.56%. The catalase activity detection result shows that the dissolved oxygen concentration of the hollow iron is increased and then stabilized.
Claims (7)
1. A preparation method of hollow ferroferric oxide drug-loaded nanoparticles is characterized in that,
the method comprises the following steps:
(1) preparing hollow ferroferric oxide nanoparticles:
dissolving ferric trichloride hexahydrate in ethylene glycol, performing ultrasonic oscillation and magnetic stirring at room temperature until the ferric trichloride is dissolved, then adding ammonium acetate, performing further ultrasonic oscillation and magnetic stirring at room temperature for 30min until the ferric trichloride is completely dissolved, then transferring the solution to a stainless steel hydrothermal kettle, placing the stainless steel hydrothermal kettle in a forced air drying oven at 200 ℃ for hydrothermal reaction for 16.5h, cooling to room temperature after the reaction is finished, collecting the solution by using a magnet, respectively washing the solution by using absolute ethyl alcohol and deionized water for four times, dispersing the solution in water, and storing the solution at 4 ℃ for later use to obtain hollow ferroferric oxide nanoparticles;
(2) preparing hollow ferroferric oxide drug-loaded nanoparticles:
and (2) uniformly mixing the hollow ferroferric oxide nanoparticles prepared in the step (1) with adriamycin, placing the mixture in a shaking table for incubation, performing magnetic attraction on the mixture by using a magnet after the incubation is finished to remove free adriamycin, dispersing the mixture in deionized water, and storing the mixture at 4 ℃ for later use to obtain the hollow ferroferric oxide drug-loaded nanoparticles.
2. The preparation method of the hollow ferroferric oxide drug-loaded nanoparticles according to claim 1, wherein the usage amount of ferric trichloride hexahydrate in the step (1) is 1.350 g.
3. The preparation method of the hollow ferroferric oxide drug-loaded nanoparticles according to claim 1, wherein the amount of the glycol used in the step (1) is 70 mL.
4. The preparation method of the hollow ferroferric oxide drug-loaded nanoparticles according to claim 1, wherein the amount of the ammonium acetate used in the step (1) is 3.854 g.
5. The preparation method of hollow ferroferric oxide drug-loaded nanoparticles according to claim 1, wherein the stainless steel hydrothermal kettle in step (1) is a polytetrafluoroethylene lining.
6. The preparation method of the hollow ferroferric oxide drug-loaded nanoparticles according to claim 1, wherein the amount of the hollow ferroferric oxide nanoparticles used in step (2) is 1mL, and the concentration is 10 mg/mL; the dosage of the adriamycin is 40 mu L, and the concentration is 25 mg/mL.
7. The preparation method of hollow ferroferric oxide drug-loaded nanoparticles according to claim 1, wherein the temperature in the shaking table is controlled to be 37 ℃ during incubation in the step (2), the rotation speed is controlled to be 100rpm, and the incubation time is 2 hours.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101698516A (en) * | 2009-11-06 | 2010-04-28 | 南京大学 | Method for preparing hollow spherical ferroferric oxide nano material |
| US20130089614A1 (en) * | 2010-06-14 | 2013-04-11 | Xuefeng Zhang | Magnetic Nanoparticles and Uses Thereof |
| CN104436199A (en) * | 2014-08-16 | 2015-03-25 | 金陵科技学院 | Preparation method of porous ferroferric oxide composite nanometre microspheres efficiently loaded with pharmorubicin |
| CN104666278A (en) * | 2015-02-13 | 2015-06-03 | 江苏大学 | Preparation method and application of magnetically-targeted medicine carrier with optically-controlled release function |
| CN107601576A (en) * | 2017-10-23 | 2018-01-19 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Ferroso-ferric oxide hollow magnetic nano particle and preparation method thereof |
| CN110615483A (en) * | 2018-06-20 | 2019-12-27 | 陈雪 | Method for preparing magnetic ferroferric oxide nanoparticles by hydrothermal method |
| CN111994935A (en) * | 2020-08-11 | 2020-11-27 | 太原理工大学 | Preparation method of porous hollow calcium carbonate drug-loaded microspheres |
-
2020
- 2020-12-04 CN CN202011412503.1A patent/CN112591802A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101698516A (en) * | 2009-11-06 | 2010-04-28 | 南京大学 | Method for preparing hollow spherical ferroferric oxide nano material |
| US20130089614A1 (en) * | 2010-06-14 | 2013-04-11 | Xuefeng Zhang | Magnetic Nanoparticles and Uses Thereof |
| CN104436199A (en) * | 2014-08-16 | 2015-03-25 | 金陵科技学院 | Preparation method of porous ferroferric oxide composite nanometre microspheres efficiently loaded with pharmorubicin |
| CN104666278A (en) * | 2015-02-13 | 2015-06-03 | 江苏大学 | Preparation method and application of magnetically-targeted medicine carrier with optically-controlled release function |
| CN107601576A (en) * | 2017-10-23 | 2018-01-19 | 广东顺德工业设计研究院(广东顺德创新设计研究院) | Ferroso-ferric oxide hollow magnetic nano particle and preparation method thereof |
| CN110615483A (en) * | 2018-06-20 | 2019-12-27 | 陈雪 | Method for preparing magnetic ferroferric oxide nanoparticles by hydrothermal method |
| CN111994935A (en) * | 2020-08-11 | 2020-11-27 | 太原理工大学 | Preparation method of porous hollow calcium carbonate drug-loaded microspheres |
Non-Patent Citations (1)
| Title |
|---|
| RUIJUN XING ET AL.: "Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles", 《NANO RESEARCH》 * |
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