CN110840858A - Preparation method and application of magnetic drug-loaded particles based on hard template method - Google Patents
Preparation method and application of magnetic drug-loaded particles based on hard template method Download PDFInfo
- Publication number
- CN110840858A CN110840858A CN201911132194.XA CN201911132194A CN110840858A CN 110840858 A CN110840858 A CN 110840858A CN 201911132194 A CN201911132194 A CN 201911132194A CN 110840858 A CN110840858 A CN 110840858A
- Authority
- CN
- China
- Prior art keywords
- drug
- mixed solution
- magnetic
- solution
- ferroferric oxide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000003814 drug Substances 0.000 title claims abstract description 63
- 229940079593 drug Drugs 0.000 title claims abstract description 56
- 239000002245 particle Substances 0.000 title claims abstract description 46
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000004793 Polystyrene Substances 0.000 claims abstract description 32
- 229920002223 polystyrene Polymers 0.000 claims abstract description 32
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000010438 heat treatment Methods 0.000 claims abstract description 29
- 239000000463 material Substances 0.000 claims abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- 239000011259 mixed solution Substances 0.000 claims description 35
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 31
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 28
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- 239000000243 solution Substances 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 14
- 229960003638 dopamine Drugs 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 14
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 13
- 239000007864 aqueous solution Substances 0.000 claims description 13
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 13
- 238000003760 magnetic stirring Methods 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- 229920001610 polycaprolactone Polymers 0.000 claims description 9
- 239000004632 polycaprolactone Substances 0.000 claims description 9
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 238000005303 weighing Methods 0.000 claims description 9
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 claims description 8
- 239000007983 Tris buffer Substances 0.000 claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 8
- 229960002918 doxorubicin hydrochloride Drugs 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 238000001291 vacuum drying Methods 0.000 claims description 8
- 229910052786 argon Inorganic materials 0.000 claims description 7
- 239000007789 gas Substances 0.000 claims description 7
- 239000002105 nanoparticle Substances 0.000 claims description 7
- 239000002244 precipitate Substances 0.000 claims description 7
- OEOIWYCWCDBOPA-UHFFFAOYSA-N 6-methyl-heptanoic acid Chemical compound CC(C)CCCCC(O)=O OEOIWYCWCDBOPA-UHFFFAOYSA-N 0.000 claims description 6
- 239000012300 argon atmosphere Substances 0.000 claims description 6
- 238000004140 cleaning Methods 0.000 claims description 6
- 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
- 239000002904 solvent Substances 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 238000011068 loading method Methods 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
- 239000012298 atmosphere Substances 0.000 claims description 3
- 239000011248 coating agent Substances 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims description 3
- 230000008020 evaporation Effects 0.000 claims description 3
- 238000004448 titration Methods 0.000 claims description 3
- 238000001132 ultrasonic dispersion Methods 0.000 claims description 3
- 230000001681 protective effect Effects 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 claims description 2
- 239000011148 porous material Substances 0.000 abstract description 4
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- 230000001276 controlling effect Effects 0.000 abstract description 2
- 238000000151 deposition Methods 0.000 abstract description 2
- 238000001027 hydrothermal synthesis Methods 0.000 abstract description 2
- 150000002484 inorganic compounds Chemical class 0.000 abstract description 2
- 229910010272 inorganic material Inorganic materials 0.000 abstract description 2
- 238000012377 drug delivery Methods 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 6
- 201000011510 cancer Diseases 0.000 description 6
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000011258 core-shell material Substances 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000010453 quartz Substances 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 239000002086 nanomaterial Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 230000009102 absorption Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000009172 bursting Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000009169 immunotherapy Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000000696 magnetic material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002539 nanocarrier Substances 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
Classifications
-
- 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
- A61K9/5005—Wall or coating material
- A61K9/501—Inorganic compounds
-
- 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
-
- 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
- A61K9/5073—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 having two or more different coatings optionally including drug-containing subcoatings
-
- 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
- A61K9/5089—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method and application of magnetic drug-loaded particles based on a hard template method. The method uses polystyrene spheres as template materials, prepares the magnetic ferroferric oxide particles with hollow pore structures through simple hydrothermal synthesis and high-temperature heat treatment, realizes effective regulation and control of the hollow pore diameter through regulating and controlling the proportion of materials, and provides possibility for depositing and doping inorganic compound molecules. Compared with the prior art, the magnetic drug-loaded particles with the macroporous structure can be obtained by using the polystyrene spheres with low cost and regular shape as the hard template, and the drug-loaded rate of the magnetic drug-loaded particles can be greatly improved.
Description
Technical Field
The invention belongs to the fields of nano material synthesis technology and nano drug-loaded biology, and particularly relates to a method for preparing magnetic ferroferric oxide drug-loaded particles with a core-shell structure by a hard template method.
Background
Cancer is a common disease and frequently encountered disease seriously harming human health, and is one of the main causes of death caused by diseases. The existing means for treating cancer mainly comprise surgical excision, chemotherapy, immunotherapy, radiotherapy and the like. Since cancer can be successfully cured by completely eradicating cancer cells, the cancer cells cannot be completely eradicated by surgical resection operation due to the influence of factors such as tumor location, infiltration and metastasis and the like, so that magnetic field guided targeted drug delivery is a promising method for achieving the purpose under the condition. The magnetic drug target transport is to guide the magnetic drug-carrying microspheres to directionally move in vivo and to perform positioning enrichment under the action of an external magnetic field. The concentration of the drug near a focus target point can be improved by in-vitro control, fixed-point targeted delivery and the like, so that the total amount of the drug required can be reduced, and the drug toxicity hazard generated at other parts in the body can be reduced. Conventional oral drugs and injections have a sharp increase in drug concentration when the drug enters the blood, and thus often have toxicity and side effects on healthy tissues. The targeted drug delivery means that the drug can be uniformly distributed around an acting object with high selectivity, so that the use dosage and the toxic and side effects of the drug are reduced, and the treatment efficiency of the drug is improved, so that the targeted drug delivery has very attractive application prospects in the treatment of some diseases, particularly in the treatment of serious diseases such as malignant tumors and the like. Controlled release of a drug refers to the formulation of a drug or other active agent in a form and with a suitable carrier to control the absorption, metabolism, and excretion of the drug in the body. The medicine is released in vivo according to the designed dosage or released at the appointed position in a certain mode within the required time range, thereby achieving the treatment purpose, which is the meaning of targeted drug delivery. Sustained release drugs are an emerging formulation for drug delivery systems that control the rate and duration of drug delivery. In various drug delivery systems that have been developed, magnetic drug-loaded particles can selectively deliver drugs to targeted pathological sites in vivo. By applying an external magnetic field, the magnetic material together with the drug molecules can move towards the targeted area and react only at the targeted location. Meanwhile, the slow release of the medicine can stabilize the sharp change of the medicine concentration in the blood plasma and prevent the side effect of the human body under the condition of large dose administration.
In view of the advantages of easy synthesis, small size, low toxicity and unique superparamagnetism, the ferroferric oxide nano particles can be widely applied to a targeted delivery system. The magnetic ferroferric oxide drug-loaded particles may be incorporated within a drug carrier system to facilitate drug-loaded nanocarriers to deliver drugs towards a desired area via external local magnetic steering. Therefore, the superparamagnetic ferroferric oxide has great clinical potential for being used for the delivery of anticancer drugs. Meanwhile, as a drug delivery system, a drug carrier should release a drug at a suitable and stable rate. However, a bursting effect is often observed, and a very small amount of drug can reach a desired site, and since most of the loaded drug is rapidly released in an initial stage, it is important to prepare drug-loaded particles having a certain core-shell structure.
Disclosure of Invention
The invention provides a novel synthetic method of a magnetic drug-loaded nano core-shell structure by using polystyrene spheres as a template material, aiming at the problems of poor biocompatibility, low drug loading rate, single structure, complicated synthetic means and the like of a magnetic nano material prepared in the traditional technology. The method prepares the magnetic ferroferric oxide particles with hollow pore structures through simple hydrothermal synthesis and high-temperature heat treatment, and can prepare the magnetic ferroferric oxide particles with different hollow pore diameters by regulating and controlling the proportion of materials. Compared with the prior art, the magnetic drug-loaded particles with the macroporous structure can be obtained by using the polystyrene spheres with low cost and regular shape as the hard template, and the drug-loaded rate of the magnetic drug-loaded particles can be greatly improved.
The technical scheme of the invention is as follows:
a preparation method of magnetic drug-loaded particles based on a hard template method comprises the following steps:
step one, preparing ferroferric oxide coated polystyrene spheres:
weighing a proper amount of sodium hydroxide particles, slowly adding the sodium hydroxide particles into diethylene glycol, magnetically stirring the mixture at room temperature to uniformly mix the sodium hydroxide particles and the diethylene glycol, heating the mixture to the temperature of between 100 and 150 ℃ in a flowing argon atmosphere, and heating the mixture for 1 to 5 hours to obtain a solution A. Weighing a proper amount of ferric trichloride, diethylene glycol and polystyrene spheres, mixing, magnetically stirring in a flowing argon atmosphere, heating to the temperature of 200 ℃ and 250 ℃, and keeping for 10-50min to obtain a mixed solution B. Quickly injecting the solution A into the mixed solution B, and continuously keeping the temperature of 200 ℃ and 250 ℃ for heating for 10-50 minutes; and after the reaction system is naturally cooled, repeatedly centrifuging and washing the product by using absolute ethyl alcohol and deionized water, and drying the product in a vacuum drying oven to obtain the ferroferric oxide coated polystyrene sphere.
Step two, preparing magnetic drug-loaded particles coated by carbon shells;
adding the ferroferric oxide coated polystyrene spheres prepared in the step one into a tris (hydroxymethyl) aminomethane buffer solution, and uniformly dispersing the polystyrene spheres by magnetic stirring to obtain a mixed solution C; and adding dopamine into the mixed solution C, continuously stirring for 8-16 hours at room temperature, repeatedly centrifuging and cleaning a reaction system product by using absolute ethyl alcohol and deionized water, and drying in a vacuum drying oven to obtain the magnetic drug-loaded particles wrapped by the dopamine. And (3) performing heat treatment, and removing the polystyrene spheres serving as template materials to obtain the magnetic drug-loaded particles coated by the carbon shells.
And the heat treatment comprises the steps of placing the magnetic drug-loaded particles coated with dopamine in a tube furnace, and carrying out high-temperature heat treatment for 1 hour in flowing argon atmosphere, so that organic dopamine can be carbonized, and hard template polystyrene is decomposed in the high-temperature heat treatment, and the magnetic drug-loaded particles coated with carbon shells with internal cavity structures are obtained.
Among them, a method for synthesizing polystyrene spheres is well known in the art.
Preferably, in the solution a prepared in the first step, the mass-to-volume ratio of sodium hydroxide to diethylene glycol is 1: 50-200 g/mL.
Preferably, in the mixed solution B prepared in the first step, the ratio of ferric trichloride, diethylene glycol and polystyrene spheres is as follows: 1-5 g: 350 mL: 5-50 g.
Preferably, the concentration of the tris buffer in step two is 10mM, and the pH is adjusted to 8 to 9 using a dilute hydrochloric acid solution.
Preferably, the mass volume ratio of the ferroferric oxide coated polystyrene spheres to the tris buffer is 1: 100-300g/mL, and the mass ratio of the ferroferric oxide coated polystyrene spheres to the dopamine is 5: 3.
Preferably, the temperature of the heat treatment is 600 ℃, and the heat treatment time is 0.5-3 h.
Preferably, the drying treatment in the above steps is drying at 60 ℃ for 12 h.
The application of the magnetic medicine carrying particles obtained by the preparation method in the aspect of medicine loading comprises the following steps:
step A: weighing stannous isooctanoate, adding the stannous isooctanoate into caprolactone under a stirring condition, stirring for 12 hours to enable the stannous isooctanoate to be uniformly mixed, transferring the mixture into a three-neck flask, introducing argon gas into the flask as inert protective gas, reacting for 12 hours at 130 ℃ under an oil bath condition, stopping introducing the argon gas after a reaction system is naturally cooled, dissolving a precipitate in chloroform, centrifuging for three times, and then centrifuging the precipitate for five times again by using absolute ethyl alcohol to obtain polycaprolactone.
And B: weighing the magnetic drug-carrying particles with the carbon shell coating and the doxorubicin hydrochloride which are prepared by the method and have the same mass, sequentially adding the magnetic drug-carrying particles and the doxorubicin hydrochloride into a polyvinyl alcohol aqueous solution, and performing ultrasonic dispersion treatment on the mixed solution to uniformly disperse the ferroferric oxide nanoparticles and the doxorubicin hydrochloride in the polyvinyl alcohol aqueous solution to obtain an aqueous mixed solution.
And C: preparing mixed solution of acetone and ethyl acetate, mixing uniformly by magnetic stirring, dissolving the polycaprolactone and the polyethylene glycol prepared in the step A in the mixed solution of acetone and ethyl acetate, and continuously stirring by magnetic stirring to uniformly mix。And D, dropwise adding the water-phase mixed solution obtained in the step B into the mixed solution of acetone and ethyl acetate by using a pear-shaped titration flask under magnetic stirring, heating in a water bath at 60 ℃ to accelerate the evaporation of the solvent, repeatedly centrifuging and cleaning the residual precipitate by absolute ethyl alcohol after the solvent is completely evaporated, and further drying in vacuum to obtain the polycaprolactone-coated ferroferric oxide drug-loaded sphere. Preferably, in the step B, the mass fraction of the polyvinyl alcohol aqueous solution is 1%, and the mass-volume ratio of the ferroferric oxide nanoparticles to the polyvinyl alcohol aqueous solution is 1-10: 600g/mL。
Preferably, in the step B, the mass fraction of the polyvinyl alcohol aqueous solution is 1%, and the mass-volume ratio of the ferroferric oxide nanoparticles to the polyvinyl alcohol aqueous solution is 1-10: 600 g/mL.
Preferably, in the step C, the volume ratio of acetone to ethyl acetate in the mixed solution of acetone and ethyl acetate is 2-6: 1.
The invention has the beneficial effects that:
1. the spherical polystyrene is adopted as a template material, the aperture and the volume can be regulated and controlled in the preparation process, and the oxygen-containing functional group on the surface is used for modification, so that the possibility is provided for depositing and doping inorganic compound molecules.
2. The magnetic microsphere with the internal cavity structure is designed and prepared to be used as the drug-loaded particle, so that the drug loading capacity of the drug-loaded material per unit mass can be effectively improved.
Detailed Description
The first embodiment is as follows:
the preparation method of the magnetic drug-loaded particles based on the hard template method comprises the following steps:
step one, preparing ferroferric oxide coated polystyrene spheres.
0.4g of sodium hydroxide particles was weighed, slowly added to a beaker containing 40mL of diethylene glycol, and mixed well by magnetic stirring at room temperature for 1 h. After the solution was stirred, it was transferred to a three-necked flask and heated at 120 ℃ for 2 hours under flowing argon atmosphere to give a yellow clear solution a. Meanwhile, 0.25g of ferric trichloride, 35mL of diethylene glycol and 1.0g of polystyrene dispersion are added into another flask, and the mixture is magnetically stirred and heated to 220 ℃ for 30 minutes under the atmosphere of flowing argon gas, so that a mixed solution B is obtained. Subsequently, the solution A was rapidly poured into the above mixed solution B, and heating was continued for 30 minutes while maintaining the temperature of 220 ℃. And after the reaction system is naturally cooled, repeatedly centrifuging the product by using absolute ethyl alcohol and deionized water, and drying the product in a vacuum drying oven at the temperature of 60 ℃ for 12 hours to obtain the ferroferric oxide coated polystyrene spheres.
And step two, preparing the magnetic drug-loaded particles coated by the carbon shells.
Weighing 0.5g of the ferroferric oxide coated polystyrene spheres prepared in the step one, adding the weighed polystyrene spheres into 100mL of tris buffer solution, magnetically stirring to disperse the polystyrene spheres in the tris buffer solution, wherein the concentration of the tris buffer solution is 10mM, and adjusting the pH value to 8.5 by using dilute hydrochloric acid. 0.3 g of dopamine was then added to the mixed solution and stirring was continued at room temperature for 12 hours. And after stirring is finished, repeatedly centrifuging and cleaning a reaction system product by using absolute ethyl alcohol and deionized water, and drying the product in a vacuum drying oven at the temperature of 60 ℃ for 12 hours to obtain the magnetic medicine-carrying particles coated with dopamine. Through heat treatment, the organic dopamine was carbonized, and the polystyrene spheres as a template material were removed. And the heat treatment is to place the magnetic medicine carrying particles coated with dopamine prepared in the step into a quartz tube, heat the quartz tube to 600 ℃ in a tube furnace in the atmosphere of flowing argon, and thermally decompose the quartz tube for 1h to obtain the magnetic medicine carrying particles coated with carbon shells.
The application of the magnetic medicine-carrying granule prepared by the preparation method comprises the following steps:
60mL of polyvinyl alcohol aqueous solution with the mass fraction of 1% is obtained through heating and stirring, 0.5g of prepared ferroferric oxide magnetic drug-carrying particles coated by a carbon shell and doxorubicin hydrochloride with the same mass are weighed and sequentially added into the polyvinyl alcohol aqueous solution, and the mixed solution is subjected to ultrasonic dispersion treatment, so that the ferroferric oxide nano particles and the doxorubicin hydrochloride are uniformly dispersed in the polyvinyl alcohol aqueous solution. Preparing 20mL of mixed solution of acetone and ethyl acetate, uniformly mixing the mixed solution by magnetic stirring, wherein the volume ratio of the acetone to the ethyl acetate is 4:1, dissolving the polycaprolactone and the polyethylene glycol prepared in the previous step in the mixed solution of the acetone and the ethyl acetate, and uniformly mixing the polycaprolactone and the polyethylene glycol by magnetic stirring. Dropwise adding the aqueous phase mixed solution obtained in the last step into a mixed organic solution of acetone and ethyl acetate by using a pear-shaped titration flask, uniformly mixing under the action of magnetic stirring, heating in a water bath at 60 ℃ to accelerate the evaporation of the solvent, repeatedly centrifuging and cleaning the residual precipitate by absolute ethyl alcohol after the solvent is completely evaporated, and further performing vacuum drying to obtain the ferroferric oxide drug-loaded sphere coated with polycaprolactone.
Example two:
in comparison with the examples, 0.5g of ferric chloride was used in the first experiment and the rest of the procedure was the same.
Example two:
in comparison with the examples, 1.0g of ferric chloride was used in the first experiment and the rest of the procedure was the same.
Claims (9)
1. A preparation method of magnetic drug-loaded particles based on a hard template method comprises the following steps:
step one, preparing ferroferric oxide coated polystyrene spheres:
weighing a proper amount of sodium hydroxide particles, slowly adding the sodium hydroxide particles into diethylene glycol, magnetically stirring the mixture at room temperature to uniformly mix the sodium hydroxide particles and the diethylene glycol, heating the mixture to the temperature of between 100 and 150 ℃ in a flowing argon atmosphere, and heating the mixture for 1 to 5 hours to obtain a solution A; weighing a proper amount of ferric trichloride, diethylene glycol and polystyrene spheres, mixing, magnetically stirring in a flowing argon atmosphere, heating to the temperature of 200 ℃ and 250 ℃, and keeping for 10-50min to obtain a mixed solution B; quickly injecting the solution A into the mixed solution B, continuously keeping the temperature at 200 ℃ and 250 ℃, and heating for 10-50 min; after the reaction system is naturally cooled, repeatedly centrifuging and washing the product by using absolute ethyl alcohol and deionized water, placing the product in a vacuum drying oven at 60 ℃, and drying for 12 hours to obtain the ferroferric oxide coated polystyrene spheres;
step two, preparing magnetic drug-loaded particles with carbon shell coating:
adding the ferroferric oxide coated polystyrene spheres prepared in the step one into a tris buffer solution, and uniformly dispersing the polystyrene spheres by magnetic stirring to obtain a mixed solution C; adding dopamine into the mixed solution C, continuously stirring for 8-16h at room temperature, repeatedly centrifuging and cleaning a reaction system product by using absolute ethyl alcohol and deionized water, and drying for 12h in a vacuum drying oven at 60 ℃ to obtain magnetic drug-loaded particles coated by dopamine; and (3) performing heat treatment, and removing the polystyrene spheres serving as template materials to obtain the magnetic drug-loaded particles coated by the carbon shells.
2. The preparation method of claim 1, wherein the heat treatment comprises placing the magnetic drug-loaded particles coated with dopamine in a tube furnace, and performing high-temperature heat treatment in an atmosphere of flowing argon, so that organic dopamine can be carbonized, and hard template polystyrene can be decomposed in the high-temperature heat treatment to obtain the carbon shell-coated magnetic drug-loaded particles with an internal cavity structure, wherein the temperature of the heat treatment is 600 ℃, and the time of the heat treatment is 0.5-3 h.
3. The preparation method according to claim 1, wherein in the solution A prepared in the first step, the mass-to-volume ratio of the sodium hydroxide to the diglycol is 1: 50-200 g/mL.
4. The preparation method according to claim 1, wherein the mixed solution B prepared in the first step comprises the following components in proportion: 1-5 g: 350 mL: 5-50 g.
5. The method according to claim 1, wherein the concentration of the tris buffer in step two is 10mM, and the pH is adjusted to 8 to 9 using a dilute hydrochloric acid solution.
6. The preparation method according to claim 1, wherein the mass-to-volume ratio of the ferroferric oxide-coated polystyrene spheres to the tris buffer solution is 1: 100-300g/mL, and the mass ratio of the ferroferric oxide coated polystyrene spheres to the dopamine is 5: 3.
7. The application of the magnetic drug-loaded particles prepared by the preparation method according to any one of claims 1 to 6 in the aspect of drug loading is characterized by comprising the following steps:
step A: weighing stannous isooctanoate, adding the stannous isooctanoate into caprolactone under a stirring condition, stirring for 12 hours to enable the stannous isooctanoate to be uniformly mixed, transferring the mixture into a three-neck flask, introducing argon gas into the flask to serve as inert protective gas, reacting for 12 hours at 130 ℃ under an oil bath condition, stopping introducing the argon gas after a reaction system is naturally cooled, dissolving a precipitate in chloroform, centrifuging for three times, and then centrifuging the precipitate for five times again by using absolute ethyl alcohol to obtain polycaprolactone;
and B: weighing the magnetic drug-carrying particles with the carbon shell coating and the doxorubicin hydrochloride which are prepared by the method and have the same mass, sequentially adding the magnetic drug-carrying particles and the doxorubicin hydrochloride into a polyvinyl alcohol aqueous solution, and performing ultrasonic dispersion treatment on the mixed solution to uniformly disperse the ferroferric oxide nanoparticles and the doxorubicin hydrochloride in the polyvinyl alcohol aqueous solution to obtain an aqueous mixed solution;
and C: preparing a mixed solution of acetone and ethyl acetate, uniformly mixing the mixed solution through magnetic stirring, dissolving polycaprolactone and polyethylene glycol prepared in the step A in the mixed solution of acetone and ethyl acetate, continuously and uniformly mixing the mixed solution through magnetic stirring, using a pear-shaped titration bottle, dropwise adding the water-phase mixed solution obtained in the step B into the mixed solution of acetone and ethyl acetate under the magnetic stirring, heating the mixed solution through a water bath at 60 ℃ to accelerate the evaporation of the solvent, repeatedly centrifuging and cleaning the residual precipitate through absolute ethyl alcohol after the solvent is completely evaporated, and further performing vacuum drying to obtain the ferroferric oxide drug-loaded spheres coated with polycaprolactone.
8. The use of claim 8, wherein in the step B, the mass fraction of the polyvinyl alcohol aqueous solution is 1%, and the mass-to-volume ratio of the ferroferric oxide nanoparticles to the polyvinyl alcohol aqueous solution is 1-10: 600 g/mL.
9. The use according to claim 8, wherein in the step C, the volume ratio of acetone to ethyl acetate in the mixed solution of acetone and ethyl acetate is 2-6: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911132194.XA CN110840858B (en) | 2019-11-19 | 2019-11-19 | Preparation method and application of magnetic drug-loaded particles based on hard template method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911132194.XA CN110840858B (en) | 2019-11-19 | 2019-11-19 | Preparation method and application of magnetic drug-loaded particles based on hard template method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110840858A true CN110840858A (en) | 2020-02-28 |
| CN110840858B CN110840858B (en) | 2021-09-17 |
Family
ID=69602083
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911132194.XA Active CN110840858B (en) | 2019-11-19 | 2019-11-19 | Preparation method and application of magnetic drug-loaded particles based on hard template method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110840858B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111863462A (en) * | 2020-07-10 | 2020-10-30 | 大连理工大学 | Ferroferric oxide/nitrogen-doped hollow carbon sphere composite material for supercapacitor and preparation method thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59122429A (en) * | 1982-12-28 | 1984-07-14 | Japan Synthetic Rubber Co Ltd | Magnetic particle for carrier of biological substance |
| CN101428220A (en) * | 2008-12-26 | 2009-05-13 | 北京化工大学 | Magnetic titanium dioxide hollow ball and preparation method thereof |
| CN105289434A (en) * | 2015-12-08 | 2016-02-03 | 河南大学 | Preparation method and application of Fe3O4@CA-beta-CD nano microspheres |
| CN105879043A (en) * | 2016-04-01 | 2016-08-24 | 江苏大学 | Preparation method of dual-targeting drug carrier based on magnetic metal organic framework material |
-
2019
- 2019-11-19 CN CN201911132194.XA patent/CN110840858B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS59122429A (en) * | 1982-12-28 | 1984-07-14 | Japan Synthetic Rubber Co Ltd | Magnetic particle for carrier of biological substance |
| CN101428220A (en) * | 2008-12-26 | 2009-05-13 | 北京化工大学 | Magnetic titanium dioxide hollow ball and preparation method thereof |
| CN105289434A (en) * | 2015-12-08 | 2016-02-03 | 河南大学 | Preparation method and application of Fe3O4@CA-beta-CD nano microspheres |
| CN105879043A (en) * | 2016-04-01 | 2016-08-24 | 江苏大学 | Preparation method of dual-targeting drug carrier based on magnetic metal organic framework material |
Non-Patent Citations (1)
| Title |
|---|
| PAULO C. MORAIS: "Synthesis of Magnetite Nanoparticles in Mesoporous Copolymer Template:A model System fo Mass-Loading COntrol", 《CHEMISTRY OF MATERIALAS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111863462A (en) * | 2020-07-10 | 2020-10-30 | 大连理工大学 | Ferroferric oxide/nitrogen-doped hollow carbon sphere composite material for supercapacitor and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110840858B (en) | 2021-09-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Studies on alginate–chitosan microcapsules and renal arterial embolization in rabbits | |
| CN103342453B (en) | The method of the monodisperse mesoporous bioactivity glass microballoon of template synthesis | |
| Chen et al. | Biodegradable hollow mesoporous organosilica-based nanosystems with dual stimuli-responsive drug delivery for efficient tumor inhibition by synergistic chemo-and photothermal therapy | |
| CN104689337B (en) | A kind of method that utilization metal-organic framework materials load 5 fluorouracils | |
| CN100344277C (en) | Nano-magnetic medicinal microglobule, its preparation method and application | |
| CN110840858B (en) | Preparation method and application of magnetic drug-loaded particles based on hard template method | |
| US20220273674A1 (en) | Extended-release drug delivery compositions | |
| CN108853494B (en) | Preparation method of temperature-triggered drug-loaded copper sulfide nanocage | |
| JP2003501379A (en) | Use of Drug-Filled Nanoparticles for Cancer Treatment | |
| CN105031651B (en) | A kind of enzyme response type magnetic nano particle and preparation method and application | |
| CN106606778B (en) | Choline phosphate-containing polymer coated core-shell type magnetic composite particle and preparation method thereof | |
| Wu et al. | Recent advances in kaolinite nanoclay as drug carrier for bioapplications: a review | |
| Wang et al. | Control of nanodiamond-doxorubicin drug loading and elution through optimized compositions and release environments | |
| CN104825488B (en) | One kind loads arsenical and preparation method and application | |
| EP1694307A2 (en) | Methods for the treatment of cancer | |
| CN111166728B (en) | Tumor-targeted composite nano-drug carrier, drug, preparation method and application | |
| CN103961713A (en) | Application of mesoporous silica based controlled release material modified by chitosan | |
| Zhang et al. | Advances in Immunomodulatory MOFs for Biomedical Applications | |
| CN110251456B (en) | Preparation method and application of nanogel | |
| CN113797226A (en) | Ammonia borane/silicon ball/mesoporous silicon dioxide nano composite particle and preparation and application thereof | |
| Deok Kong et al. | Externally triggered on-demand drug release and deep tumor penetration | |
| CN108464973B (en) | Preparation method of growth factor receptor blocker medicine for targeted therapy of lung diseases | |
| Deshmukh et al. | Microspheres: As new drug delivery system | |
| US20220127559A1 (en) | Microrobot and Method of Manufacturing the Microrobot | |
| CN107303286B (en) | Gelatin hybrid compound and preparation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |