CN110151729B - Preparation method of multifunctional mesoporous silicon drug carrier with core-shell structure - Google Patents
Preparation method of multifunctional mesoporous silicon drug carrier with core-shell structure Download PDFInfo
- Publication number
- CN110151729B CN110151729B CN201910537009.9A CN201910537009A CN110151729B CN 110151729 B CN110151729 B CN 110151729B CN 201910537009 A CN201910537009 A CN 201910537009A CN 110151729 B CN110151729 B CN 110151729B
- Authority
- CN
- China
- Prior art keywords
- solution
- beta
- msn
- drug
- pnipam
- 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.)
- Active
Links
Images
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5115—Inorganic compounds
-
- 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
- A61K9/5123—Organic compounds, e.g. fats, sugars
-
- 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
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of drug carriers, and particularly relates to a preparation method of a multifunctional mesoporous silicon drug carrier with a core-shell structure. The invention relates to a beta-cyclodextrin-poly (N-isopropylacrylamide) star polymer (beta-CD- (PNIPAM)7) The surface of ferrocene functionalized mesoporous silicon dioxide (MSN-Fc) is modified through the action of a host and an object to form an intelligent nano valve, and the temperature/redox dual-response drug carrier with a core-shell structure is prepared. Preparation of the inventionThe composite nano particles have strong drug loading capacity on drugs, the drug loading capacity in various simulated drugs can reach more than 30 percent, and the drug loading capacity reported in the prior art is mostly 5 to 10 percent; and the controlled release of the drug under the temperature and the multiple stimulus response of oxidation reduction can be realized, and the drug can be rapidly released under the condition that the temperature is higher than 37 ℃ or an oxidant exists.
Description
Technical Field
The invention belongs to the technical field of drug carriers, and particularly relates to a preparation method of a multifunctional mesoporous silicon drug carrier with a core-shell structure.
Background
In the past decades, in order to improve the biotoxicity and low water solubility of drugs, various nanocarriers have been designed to protect drug molecules from the immune system and indirectly improve the solubility of drugs. Many studies have focused on the functionalization of drug delivery vehicles formed from cyclodextrins, but the vehicles formed from host-guest interactions between cyclodextrins and functional molecules have the disadvantages of low mechanical strength, weak loading capacity, single environmental stimulus response, etc., and are not well adapted to the complex pathological environments of the body, and are limited in clinical treatment.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a preparation method of a multifunctional mesoporous silicon drug carrier with a core-shell structure.
The technical scheme for solving the technical problems is as follows: a preparation method of a multifunctional mesoporous silicon drug carrier with a core-shell structure comprises the following steps:
(1) ferrocene (Fc), mesoporous silicon oxide (MSN), poly (N-isopropylacrylamide) (PNIPAM) and beta-cyclodextrin (beta-CD) are taken as raw materials to respectively prepare the ferrocene modified mesoporous silicon oxide (MSN-Fc) and the poly (N-isopropylacrylamide) modified cyclodextrin (beta-CD- (PNIPAM)7)；
(2) Mixing MSN-Fc and beta-CD- (PNIPAM)7Respectively dissolving in DMF and ultrapure water to respectively obtain MSN-Fc solution and beta-CD- (PNIPAM)7A solution;
(3) adding the drug into the MSN-Fc solution obtained in the step (2), stirring and dissolving, loading for 24-48h, and dropwise adding the MSN-Fc solution dissolved with the drug into beta-CD- (PNIPAM)7And compounding the solution for 4-12h, and dialyzing with ultrapure water to obtain the composite drug-loaded nano particles.
Further, in the step (1)The MSN-Fc is prepared by bridging and bonding MCM-41 and Fc-COOH through a silane coupling agent; the beta-CD- (PNIPAM)7Is prepared by an atom transfer radical polymerization method.
Further, the MSN-Fc is prepared as follows:
(1) dissolving Cetyl Trimethyl Ammonium Bromide (CTAB) and 2mol/L NaOH solution in deionized water, heating the solution to 80 ℃, and reacting for 1 h; continuously dropwise adding ethyl orthosilicate into the solution, and violently stirring the mixture for 2 hours to obtain a white precipitate; filtering the white precipitate, repeatedly washing with methanol and deionized water, vacuum drying, sintering the dried product by using a muffle furnace to remove a CTAB template, and preheating and sintering at 550 ℃ for 5.5h to obtain a solid product MCM-41;
(2) placing the solid product obtained in the step (1) in a round-bottom flask, carrying out oil bath at 165 ℃, activating in vacuum for 10h, adding anhydrous toluene, suspending the anhydrous toluene in the anhydrous toluene, and reacting the anhydrous toluene with the anhydrous toluene2Stirring in the atmosphere, and simultaneously adding (3-aminopropyl) triethoxysilane into the solution; then heating the solution to reflux for 12h, centrifuging to collect the product and washing with toluene and methanol; vacuum drying the product obtained by centrifugation for 12 h;
(3) putting the product obtained in the step (2) into a round-bottom flask, and carrying out vacuum drying for 12h under the condition of water bath at 60 ℃ to remove water; the dried product was added to a DMF solution containing ferrocene carboxylate (Fc-COOH), N-hydroxysuccinimide and 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride in N2The mixture is stirred for 48 hours at the temperature of 18-25 ℃; and (3) centrifugally separating the product, washing the product for 3 times by using methanol, and drying the product in a vacuum drying oven for 8 hours to obtain the final product MSN-Fc.
The beta-CD- (PNIPAM)7The preparation method comprises the following steps:
(1) dissolving beta-CD in N-methylpyrrolidone under stirring at 0 ℃, continuously adding 2-bromine isobutyryl bromide, stirring the reaction mixture for 2 hours at 0 ℃, and stirring for 48 hours at 20 ℃; the product was added to dichloromethane and washed with 0.1mol/L HCl solution, saturated NaHCO3Washing the solution with deionized water; precipitating the organic layer, and drying in vacuum at 40 ℃ to obtain acyl bromide beta-cyclodextrin;
(2) dispersing acyl brominated beta-cyclodextrin and N-isopropyl acrylamide into deionized water to obtain a dispersion solution; is charged into N2Dissolving a mixture of cuprous chloride and pentamethyldiethylenetriamine in acetone/water, adding the mixture into the dispersion solution, and reacting for 24 hours at 35 ℃; washing the product with deionized water, dialyzing for 48h, and freeze-drying to obtain the product beta-CD- (PNIPAM)7。
Further, in the step (2), MSN-Fc is dissolved in DMF, ultrasonic dispersion is carried out for 0.5-1.5h, magnetic stirring is carried out for 12-24h, and the concentration of the obtained MSN-Fc solution is 0.1-0.5 mg/mL; the resulting beta-CD- (PNIPAM)7The concentration of the solution is 0.2-1.0 mg/mL.
Further, in the step (3), the drug is 5-fluorouracil, naproxen, indomethacin, adriamycin or diclofenac sodium.
Further, in the step (3), the dosage ratio of the medicine to the MSN-Fc solution is 1 mg: (1-10) mL; the MSN-Fc solution and beta-CD- (PNIPAM)7The volume ratio of the solution is 1: (1-10).
Further, the particle diameter of the composite drug-loaded nanoparticle obtained in the step (3) is 100-200nm, and the pore diameter is 2-3 nm.
The invention has the characteristics and beneficial effects that:
1. mesoporous silica nano particles (MSNs) have the characteristics of ordered mesoporous structure, large specific surface area, uniform size, controllable aperture, high mechanical stability and good biocompatibility. In physiological environments, there are large differences between normal cells and tumor cells, such as higher temperature and weak acidity. Based on the characteristics, the surface of the mesoporous silica is provided with the nano valve which can be controlled by external environment stimulation, when the nano particles reach the microenvironment where the tumor cells are, the nano valve is damaged under the conditions of temperature and hydrogen peroxide, and the object molecules are released.
2. Ferrocene (Fc) is a biocompatible molecule with a hydrophobic sandwich structure, and can be hydrophobically wrapped with beta-cyclodextrin to form a supramolecular complex. In the presence of an oxidizing agent, ferrocene is oxidized to positively charged ferrocene
Ionic, stable supramolecular complex structures are destroyed.
3. The invention relates to a beta-cyclodextrin-poly (N-isopropylacrylamide) star polymer (beta-CD- (PNIPAM)7) The surface of ferrocene functionalized mesoporous silicon dioxide (MSN-Fc) is modified through the action of a host and an object to form an intelligent nano valve, and the temperature/redox dual-response drug carrier with a core-shell structure is prepared.
4. The composite nano particles prepared by the invention have strong drug loading capacity on drugs, the drug loading capacity in various simulated drugs can reach more than 30%, and the drug loading capacity reported in the prior art is mostly 5-10%; and the controlled release of the drug under the temperature and the multiple stimulus response of oxidation reduction can be realized, and the drug can be rapidly released under the condition that the temperature is higher than 37 ℃ or an oxidant exists.
Drawings
FIG. 1 is a schematic view of a multifunctional mesoporous silicon drug carrier with a core-shell structure synthesized by the present invention;
FIG. 2 is a transmission electron microscope picture of the product obtained in example 1 of the present invention (A is MSN, B is MSN-Fc, and C is the multifunctional mesoporous silicon drug carrier);
FIG. 3 is a drug release profile of the drug delivery vehicle obtained in example 1 of the present invention.
Detailed Description
The principles and features of this invention are described below in conjunction with examples, which are set forth to illustrate, but are not to be construed to limit the scope of the invention.
The preparation method of the raw material MSN-Fc used in the embodiment of the invention is as follows:
(1) dissolving 1.0g of hexadecyl trimethyl ammonium bromide and 3.5mL of NaOH (2M) in 480mL of deionized water, heating the solution to 80 ℃, and reacting for 1 h; slowly dropwise adding 5.0mL of Tetraethoxysilane (TEOS) into the solution, and violently stirring the mixture for 2 hours to obtain a white precipitate; filtering the white precipitate, repeatedly washing with methanol and deionized water, vacuum drying (60 ℃), sintering the dried product by using a muffle furnace to remove a CTAB template, and preheating and sintering at 550 ℃ for 5.5h to obtain a solid product MCM-41;
(2) 1.0g of the solid product obtained in step (1) was placed in a round-bottomed flask, oil-immersed at 165 ℃ and activated in vacuo for 10 hours, and 75mL of anhydrous toluene was added, suspended in anhydrous toluene and stirred under N2Stirring in the atmosphere while adding 0.75mL (3-aminopropyl) triethoxysilane to the solution; then the solution was heated to reflux for 12 h; centrifuging, collecting the product, washing the product with toluene and methanol, and vacuum-drying the product for 12 h;
(3) putting the product obtained in the step (2) into a round-bottom flask, and carrying out vacuum drying for 12h under the condition of water bath at 60 ℃ to remove water; 0.1g of the dried product was added to a solution of 0.03g of ferrocene carboxylate (Fc-COOH), 0.045g N-hydroxysuccinimide (NHS) and 0.09g of 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC hydrochloride) in DMF (10mL) under N2The mixture was stirred at room temperature for 48 h; and (3) centrifugally separating the product, washing the product for 3 times by using methanol, and drying the product in a vacuum drying oven for 8 hours to obtain the final product MSN-Fc.
Raw material beta-CD- (PNIPAM) used in the examples of the present invention7The preparation method comprises the following steps:
(1) beta-CD (2270mg) was dissolved in 14.0mL of N-methylpyrrolidinone (NMP) with stirring at 0 deg.C, and 2-bromoisobutyryl bromide (3.7mL) was added; the reaction mixture was stirred at 0 ℃ for 2h, 20 ℃ for 48 h; the product was added to 50.0mL of dichloromethane and washed with 0.1mol/L HCl solution, saturated NaHCO3Washing the solution with deionized water; precipitating the organic layer, and drying the organic layer at 40 ℃ in vacuum to obtain acyl bromide beta-cyclodextrin (beta-CD-Br);
(2) dispersing 250mg of the product obtained in the step (1) and 760mg of N-isopropylacrylamide (NIPAM) into 2.0mL of deionized water to obtain a dispersion solution; is charged into N2After 30 minutes, a mixture of cuprous chloride (13.4mg) and pentamethyldiethylenetriamine (42mg) was dissolved in 1.5mL of acetone/water and slowly added to the above dispersion solution; reacting at 35 deg.C for 24h, washing the product with deionized water and dialyzing for 48h, and freeze-drying to obtain the product beta-CD- (PNIPAM)7。
Example 1
A preparation method of a multifunctional mesoporous silicon drug carrier with a core-shell structure comprises the following steps:
(1) ferrocene (Fc), mesoporous silicon oxide (MSN), poly (N-isopropylacrylamide) (PNIPAM) and beta-cyclodextrin (beta-CD) are taken as raw materials to respectively prepare the ferrocene modified mesoporous silicon oxide (MSN-Fc) and the poly (N-isopropylacrylamide) modified cyclodextrin (beta-CD- (PNIPAM)7)；
(2) Dissolving MSN-Fc into 2mL of DMF solution, performing ultrasonic dispersion for 2h, and performing magnetic stirring for 15h to obtain 0.2mg/mL of MSN-Fc solution; mixing beta-CD- (PNIPAM)7Dissolving in 3mL of ultrapure water to obtain 0.4mg/mL of beta-CD- (PNIPAM)7A solution;
(3) adding 0.64mg of adriamycin into 2mL of the MSN-Fc solution obtained in the step (2), dissolving the solution with stirring, and after 24 hours of loading, adding the MSN-Fc solution dissolved with adriamycin into 3mL of beta-CD- (PNIPAM) at the speed of 1-2 drops/5 s7In the solution, after compounding for 12h, dialyzing for 12h by ultrapure water to obtain the composite drug-loaded nano particles, wherein the drug-loaded amount is 34.8%.
Example 2
A preparation method of a multifunctional mesoporous silicon drug carrier with a core-shell structure comprises the following steps:
(1) ferrocene (Fc), mesoporous silicon oxide (MSN), poly (N-isopropylacrylamide) (PNIPAM) and beta-cyclodextrin (beta-CD) are taken as raw materials to respectively prepare the ferrocene modified mesoporous silicon oxide (MSN-Fc) and the poly (N-isopropylacrylamide) modified cyclodextrin (beta-CD- (PNIPAM)7)；
(2) Dissolving MSN-Fc into 5mL of DMF solution, performing ultrasonic dispersion for 2h, and performing magnetic stirring for 15h to obtain 0.1mg/mL of MSN-Fc solution; mixing beta-CD- (PNIPAM)7Dissolving in 3mL of ultrapure water to obtain 0.3mg/mL of beta-CD- (PNIPAM)7A solution;
(3) adding 0.96mg of 5-fluorouracil to 2mL of the MSN-Fc solution of step (2), dissolving with stirring, and after 24 hours of loading, adding the MSN-Fc solution with the dissolved drug to 16mL of beta-CD- (PNIPAM) at a rate of 1-2 drops/5 s7In the solution, after compounding for 12h, dialyzing for 12h by ultrapure water to obtain the composite drug-loaded nano particles, wherein the drug-loaded amount is 30.34%.
In order to verify the controlled release and sustained release effects of the drug carrier obtained in the invention, the composite drug-loaded nanoparticle obtained in example 1 was tested by changing the environmental temperature and adding an oxidant, and the specific results are shown in fig. 3:
as can be seen from FIG. 2, the mesoporous diameter of the composite drug-loaded nanoparticle obtained by the invention is 2-3nm, the particle diameter of the composite nanoparticle is 100-200nm, and the structure is regular. As can be seen from FIG. 3, the drug release of the composite drug-loaded nanoparticle obtained by the invention can be realized by adjusting the temperature and H of the buffer solution2O2The concentration.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (4)
1. A preparation method of a multifunctional mesoporous silicon drug carrier with a core-shell structure is characterized by comprising the following steps:
(1) ferrocene Fc, mesoporous silicon oxide MSN, poly (N-isopropyl acrylamide) PNIPAM and beta-cyclodextrin beta-CD are taken as raw materials to respectively prepare ferrocene modified mesoporous silicon oxide MSN-Fc and poly (N-isopropyl acrylamide) modified cyclodextrin beta-CD- (PNIPAM)7；
(2) Mixing MSN-Fc and beta-CD- (PNIPAM)7Dissolving in DMF and ultrapure water to obtain MSN-Fc solution and beta-CD- (PNIPAM)7A solution;
(3) adding the drug into the MSN-Fc solution obtained in the step (2), stirring and dissolving, loading for 24-48h, and dropwise adding the MSN-Fc solution dissolved with the drug into beta-CD- (PNIPAM)7Compounding in the solution for 4-12h, and dialyzing with ultrapure water to obtain composite drug-loaded nanoparticles;
in the step (1), the MSN-Fc is prepared by linking MCM-41 and Fc-COOH through bridging of a silane coupling agent; the beta-CD- (PNIPAM)7Is prepared by an atom transfer radical polymerization method;
in the step (3), the dosage ratio of the medicine to the MSN-Fc solution is 1 mg: (1-10) mL; the MSN-Fc solution and beta-CD- (PNIPAM)7The volume ratio of the solution is 1: (1-10); the concentration of the MSN-Fc solution is 0.1-0.5 mg/mL; the beta-CD-(PNIPAM)7The concentration of the solution is 0.2-1.0 mg/mL; the drug is 5-fluorouracil or adriamycin; the particle size of the composite drug-carrying nano particle obtained in the step (3) is 100-200nm, and the aperture is 2-3 nm.
2. The method of claim 1, wherein the MSN-Fc is prepared as follows:
(1) dissolving cetyl trimethyl ammonium bromide and 2mol/L NaOH solution in deionized water, heating the solution to 80 ℃, and reacting for 1 h; continuously dropwise adding ethyl orthosilicate into the solution, and violently stirring the mixture for 2 hours to obtain a white precipitate; filtering the white precipitate, repeatedly washing with methanol and deionized water, vacuum drying, sintering the dried product by using a muffle furnace to remove a CTAB template, and preheating and sintering at 550 ℃ for 5.5h to obtain a solid product MCM-41;
(2) placing the solid product obtained in the step (1) in a round-bottom flask, carrying out oil bath at 165 ℃, activating in vacuum for 10h, adding anhydrous toluene, suspending the anhydrous toluene in the anhydrous toluene, and reacting the anhydrous toluene with the anhydrous toluene2Stirring in the atmosphere, and simultaneously adding (3-aminopropyl) triethoxysilane into the solution; then heating the solution to reflux for 12h, centrifuging to collect the product and washing with toluene and methanol; vacuum drying the product obtained by centrifugation for 12 h;
(3) putting the product obtained in the step (2) into a round-bottom flask, and carrying out vacuum drying for 12h under the condition of water bath at 60 ℃ to remove water; the dried product was added to a DMF solution containing ferrocene carboxylate Fc-COOH, N-hydroxysuccinimide and 1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride in N2The mixture is stirred for 48 hours at the temperature of 18-25 ℃; and (3) centrifugally separating the product, washing the product for 3 times by using methanol, and drying the product in a vacuum drying oven for 8 hours to obtain the final product MSN-Fc.
3. The method of claim 1, wherein the beta-CD- (PNIPAM)7The preparation method comprises the following steps:
(1) dissolving beta-CD in N-methyl pyrrolidone at 0 deg.C under stirring, adding 2-bromoisobutyryl bromide, and reacting at 0 deg.CStirring for 2h, and stirring for 48h at 20 ℃; the product was added to dichloromethane and washed with 0.1mol/L HCl solution, saturated NaHCO3Washing the solution with deionized water; precipitating the organic layer, and drying in vacuum at 40 ℃ to obtain acyl bromide beta-cyclodextrin;
(2) dispersing acyl brominated beta-cyclodextrin and N-isopropyl acrylamide into deionized water to obtain a dispersion solution; is charged into N2Dissolving a mixture of cuprous chloride and pentamethyldiethylenetriamine in acetone/water, adding the mixture into the dispersion solution, and reacting for 24 hours at 35 ℃; washing the product with deionized water, dialyzing for 48h, and freeze-drying to obtain the product beta-CD- (PNIPAM)7。
4. The preparation method according to claim 1, wherein in the step (2), MSN-Fc is dissolved in DMF, ultrasonically dispersed for 0.5-1.5h, and magnetically stirred for 12-24 h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910537009.9A CN110151729B (en) | 2019-06-20 | 2019-06-20 | Preparation method of multifunctional mesoporous silicon drug carrier with core-shell structure |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910537009.9A CN110151729B (en) | 2019-06-20 | 2019-06-20 | Preparation method of multifunctional mesoporous silicon drug carrier with core-shell structure |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110151729A CN110151729A (en) | 2019-08-23 |
| CN110151729B true CN110151729B (en) | 2022-05-06 |
Family
ID=67625364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910537009.9A Active CN110151729B (en) | 2019-06-20 | 2019-06-20 | Preparation method of multifunctional mesoporous silicon drug carrier with core-shell structure |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110151729B (en) |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102492095A (en) * | 2011-12-08 | 2012-06-13 | 北京化工大学 | Construction of bio-reducible efficient cation gene vectors taking polysaccharides as frameworks with ATRP (Atom Transfer Radical Polymerization) method |
| CN102964538A (en) * | 2012-12-03 | 2013-03-13 | 西北工业大学 | Method for preparing environmentally responsive monodisperse cyclodextrin polymer hollow microspheres |
| CN103524751A (en) * | 2013-09-11 | 2014-01-22 | 江南大学 | Preparation method of double-sensitivity cyclodextrin supermolecule aggregate |
| CN106474485A (en) * | 2015-08-28 | 2017-03-08 | 南京理工大学 | A kind of voltage-stimuli responsive type intelligent nano container and preparation method thereof |
| CN106902356A (en) * | 2015-12-18 | 2017-06-30 | 南京理工大学 | A kind of double-response multi-medicament Transmission system based on cyclodextrin |
| CN108553644A (en) * | 2018-05-11 | 2018-09-21 | 湖北大学 | The more stimuli responsive type pharmaceutical carriers of double valve and preparation method thereof based on mesoporous silicon/cyclodextrin/Zinc oxide quantum dot structure |
| CN109053960A (en) * | 2018-07-18 | 2018-12-21 | 常州大学 | A kind of preparation method of temperature sensitive beta-cyclodextrin nanoparticle |
-
2019
- 2019-06-20 CN CN201910537009.9A patent/CN110151729B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102492095A (en) * | 2011-12-08 | 2012-06-13 | 北京化工大学 | Construction of bio-reducible efficient cation gene vectors taking polysaccharides as frameworks with ATRP (Atom Transfer Radical Polymerization) method |
| CN102964538A (en) * | 2012-12-03 | 2013-03-13 | 西北工业大学 | Method for preparing environmentally responsive monodisperse cyclodextrin polymer hollow microspheres |
| CN103524751A (en) * | 2013-09-11 | 2014-01-22 | 江南大学 | Preparation method of double-sensitivity cyclodextrin supermolecule aggregate |
| CN106474485A (en) * | 2015-08-28 | 2017-03-08 | 南京理工大学 | A kind of voltage-stimuli responsive type intelligent nano container and preparation method thereof |
| CN106902356A (en) * | 2015-12-18 | 2017-06-30 | 南京理工大学 | A kind of double-response multi-medicament Transmission system based on cyclodextrin |
| CN108553644A (en) * | 2018-05-11 | 2018-09-21 | 湖北大学 | The more stimuli responsive type pharmaceutical carriers of double valve and preparation method thereof based on mesoporous silicon/cyclodextrin/Zinc oxide quantum dot structure |
| CN109053960A (en) * | 2018-07-18 | 2018-12-21 | 常州大学 | A kind of preparation method of temperature sensitive beta-cyclodextrin nanoparticle |
Non-Patent Citations (5)
| Title |
|---|
| Enzyme and voltage stimuli-responsive controlled release system based on β-cyclodextrin-capped mesoporous silica nanoparticles;Yu Xiao et al;《Dalton Trans》;20151231;第44卷(第9期);全文 * |
| Poly(N-isopropylacrylamide)-Coated β-Cyclodextrin-Capped Magnetic Mesoporous Silica Nanoparticles Exhibiting Thermal and pH Dual Response for Triggered Anticancer Drug Delivery;Ali Pourjavadi et al;《International Journal of Polymeric Materials and Polymeric Biomaterials》;20170222;第1页摘要，第7-9页 * |
| Synthesis of star poly(N-isopropylacrylamide) by β-cyclodextrin core initiator via ATRP approach in water;Marcos Roberto Mauricio et al;《Reactive and Functional Polymers》;20110910;第71卷(第12期);全文 * |
| Synthesis of temperature/pH dual-sensitive supramolecular micelles from β-cyclodextrin-poly(N-isopropylacrylamide) star polymer for drug delivery;Zaishuai Zhou et al;《Colloids and Surfaces B: Biointerfaces》;20180818;第172卷;第137页2.2项 * |
| 硅基介孔材料为载体的酶固定化和刺激敏感的缓释体系;肖宇;《中国博士学位论文全文数据库（工程科技I辑）》;20150815;摘要，第53页4.2项，第55-56页4.3.3项，第59页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110151729A (en) | 2019-08-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gao et al. | Mesoporous silica nanoparticles capped with graphene quantum dots as multifunctional drug carriers for photo-thermal and redox-responsive release | |
| Pooresmaeil et al. | Surface modification of graphene oxide with stimuli-responsive polymer brush containing β-cyclodextrin as a pendant group: Preparation, characterization, and evaluation as controlled drug delivery agent | |
| CN109589418B (en) | Schiff base copolymer coated mesoporous silica drug-loaded nanoparticle with pH responsiveness and preparation method and application thereof | |
| CN107854449B (en) | Nano composite microsphere with drug controlled release performance and preparation method and application thereof | |
| Francis et al. | Polymer grafted inorganic nanoparticles, preparation, properties, and applications: a review | |
| CN109549933B (en) | pH-responsive nano carrier and preparation method and application thereof | |
| Sheng et al. | pH-sensitive drug delivery based on chitosan wrapped graphene quantum dots with enhanced fluorescent stability | |
| CN107865972B (en) | Preparation method and application of multifunctional membrane-controlled targeting nano-carrier with tracing and targeting drug delivery functions | |
| Samadian et al. | A de novo theranostic nanomedicine composed of PEGylated graphene oxide and gold nanoparticles for cancer therapy | |
| CN108704133B (en) | Janus particle with chemotherapy/photothermal synergistic effect and preparation method thereof | |
| Papa et al. | Dispersion of titanate nanotubes for nanomedicine: comparison of PEI and PEG nanohybrids | |
| CN102198117B (en) | Thermosensitive polymeric microcapsules and preparation method and use thereof | |
| CN103013016B (en) | Medical carrier and medical composition and preparation method thereof | |
| KR101994775B1 (en) | Porous silica nanocomposite drug delivery system and method for reparing the same | |
| Tayebee et al. | Fe3O4@ SiO2-NH2 as an efficient nanomagnetic carrier for controlled loading and release of acyclovir | |
| Shafiei-Irannejad et al. | Synthesis and characterization of novel hybrid nanomaterials based on β-cyclodextrine grafted halloysite nanotubes for delivery of doxorubicin to MCF-7 cell line | |
| CN113975235B (en) | Fucoxanthin-delivering brown alginate oligosaccharide-mesoporous silica nanocomposite | |
| CN110151729B (en) | Preparation method of multifunctional mesoporous silicon drug carrier with core-shell structure | |
| CN112569367B (en) | 5-fluorouracil-mesoporous silica-sodium alginate drug delivery system and preparation method thereof | |
| CN109260176B (en) | Tumor-specific cleavable PEG (polyethylene glycol) nanoparticle as well as preparation method and application thereof | |
| CN111297829A (en) | Modified glucan-coated core-shell composite nanoparticle and preparation method thereof | |
| CN112402394A (en) | BCG complex adsorbing nano-drug carrier by utilizing positive and negative charge characteristics and preparation method thereof | |
| CN113663084B (en) | Mesoporous silica prodrug nanoparticle for photothermal therapy and chemotherapy as well as preparation method and application thereof | |
| Sánchez-Orozco et al. | β-Cyclodextrin-functionalized mesocellular silica foams as nanocarriers of doxorubicin | |
| JP4873396B2 (en) | Metal oxide nanofiber / polysaccharide complex |
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 |