CN111214655A - Preparation method of drug sustained-release system with pH and near-infrared dual responses - Google Patents
Preparation method of drug sustained-release system with pH and near-infrared dual responses Download PDFInfo
- Publication number
- CN111214655A CN111214655A CN202010102120.8A CN202010102120A CN111214655A CN 111214655 A CN111214655 A CN 111214655A CN 202010102120 A CN202010102120 A CN 202010102120A CN 111214655 A CN111214655 A CN 111214655A
- Authority
- CN
- China
- Prior art keywords
- graphene oxide
- methotrexate
- mesoporous silica
- sodium alginate
- drug
- 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.)
- Pending
Links
Images
Classifications
-
- 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
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
-
- 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
- A61K9/513—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)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Nanotechnology (AREA)
- Biomedical Technology (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation method of a drug sustained-release system with pH and near-infrared dual responses. The method comprises the following steps: preparing graphene oxide, preparing graphene oxide/aminated mesoporous silica, preparing methotrexate/graphene oxide/aminated mesoporous silica, and preparing a methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained-release system. The invention has the beneficial effects that: the amino group on the surface of the aminated mesoporous silica and the carboxyl group on the sodium alginate have amidation reaction, so that an amido bond can be generated to coat the sodium alginate on the surface, and the blocking effect on the methotrexate serving as a medicament in mesopores is achieved. Due to the fact that the amido bond has certain pH sensitivity and the graphene oxide has the characteristic of better light-to-heat conversion, the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system with dual responses of pH and near infrared light is obtained, and the purpose of drug controlled release can be achieved through dual stimulation of the near infrared light and the pH.
Description
Technical Field
The invention relates to a preparation method of a drug sustained-release system with pH and near infrared dual responses, belonging to the field of material synthesis and biomedicine.
Technical Field
Graphene oxide has received extensive attention from the scientific community due to its good biocompatibility, unique structural characteristics and relatively low cost. Graphene oxide has proven to be a highly efficient emerging carrier that can be used to deliver anticancer drugs, proteins, gene drugs and bio-imaging agents in cells. Most importantly, the graphene oxide is a photosensitive material with high near infrared light absorption and has potential photo-thermal treatment capability in vivo and in vitro. The mesoporous silica is often used for constructing a stimulus-responsive drug controlled release system due to its characteristics of large specific surface area, pore volume, controllable pore size, easy surface functionalization and the like. Although mesoporous silica has been used in the field of sustained drug release, there are some disadvantages, such as premature or burst release of the drug. Therefore, sodium alginate was chosen to solve the above problems. Sodium alginate is an anionic hydrophilic polysaccharide with high pH sensitivity, has wide application in the field of medicine due to good biodegradability, biocompatibility and chelating capacity, and is applied to the fields of tissue engineering, nutrition supplementation, drug delivery and the like at present.
The surface layer of the graphene oxide nanosheet is coated with a silicon source, the graphene oxide/aminated mesoporous silica nanocomposite can be formed through reaction, the graphene oxide/aminated mesoporous silica is added into a methotrexate solution, methotrexate can be bound to mesopores of the silica through physical adsorption, so that methotrexate/graphene oxide/aminated mesoporous silica is obtained, finally, the methotrexate/graphene oxide/aminated mesoporous silica is added into a sodium alginate solution activated by 1-ethyl-3-dimethylaminopropyl-carbodiimide hydrochloride and N-hydroxysuccinimide, and because carboxyl on the sodium alginate and amino on the surface of the graphene oxide/aminated mesoporous silica are subjected to amidation reaction, thereby generating amido bond to coat the sodium alginate on the surface and playing a role in plugging the medicine methotrexate in the mesopores. Due to the fact that the amido bond has certain pH sensitivity and the graphene oxide has the characteristic of better light-to-heat conversion, the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system with dual responses of pH and near infrared light is obtained, and the purpose of drug controlled release can be achieved through dual stimulation of the near infrared light and the pH.
Disclosure of Invention
The invention aims to provide a preparation method of a drug sustained-release system with pH and near-infrared dual responses.
The invention relates to a preparation method of a drug sustained-release system with pH and near infrared dual response, which comprises the following steps:
a. preparing graphene oxide: slowly adding a certain amount of potassium permanganate and graphite powder into a mixed solution of concentrated sulfuric acid and phosphoric acid, heating and stirring in a water bath at 50 ℃ for 12 hours, cooling to room temperature, pouring into an ice water bath containing hydrogen peroxide, standing overnight, centrifugally washing a product to remove residual acid, naturally airing and grinding to obtain graphene oxide;
b. preparing graphene oxide/aminated mesoporous silica: dissolving the prepared graphene oxide in 50mL of deionized water, performing ultrasonic dispersion for 2h, adding a certain amount of hexadecyl trimethyl ammonium bromide when the graphene oxide solution is completely yellow and no obvious solid can be seen, stirring for 2h at 40 ℃, adding a certain amount of sodium hydroxide, continuously stirring for 0.5h, then adding a certain amount of ethyl orthosilicate and 3-aminopropyl triethoxysilane, stopping after reacting for 12h, repeatedly washing and drying with deionized water and anhydrous ethanol, placing the dried product into a mixed solution of anhydrous ethanol and ammonium nitrate, refluxing for 24h at 60 ℃ to remove a template agent hexadecyl trimethyl ammonium bromide, repeating for 3 times, repeatedly washing the product with anhydrous ethanol and deionized water, drying at 60 ℃, and grinding to obtain graphene oxide/aminated mesoporous silicon dioxide;
c. preparing methotrexate/graphene oxide/aminated mesoporous silica: weighing a certain amount of graphene oxide/aminated mesoporous silica, adding the graphene oxide/aminated mesoporous silica into 40mL of methotrexate solution with a certain concentration, magnetically stirring for 24h, and then carrying out centrifugal separation to obtain methotrexate/graphene oxide/aminated mesoporous silica;
d. preparing a methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system: dissolving a certain amount of sodium alginate in a phosphate buffer solution with the pH value of 5.5, adding a certain amount of 1-ethyl-3-dimethylaminopropyl-carbodiimide hydrochloride and N-hydroxysuccinimide, magnetically stirring for 45min at room temperature, adding the methotrexate/graphene oxide/aminated mesoporous silica prepared in the step c into the sodium alginate solution, magnetically stirring for 12h, placing the obtained dispersion in a watch glass, and freeze-drying for 24h at-45 ℃ to obtain the methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained-release system;
e. the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained release system is used for in-vitro release of methotrexate under different pH conditions: respectively preparing phosphate buffer solutions with pH values of 5.0, 6.8 and 7.4, taking 600mg of the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system prepared in the step d, placing the system into a dialysis bag with a molecular interception amount of 3500, respectively placing the dialysis bag into 50mL of phosphate buffer solutions with different pH values, carrying out in-vitro release of the drugs by magnetic stirring at constant temperature of 37 ℃, taking out 5mL of the solution every 60min during the drug release process, measuring the amount of the released methotrexate, and simultaneously supplementing 5mL of fresh phosphate buffer solution. The concentration of methotrexate is determined by measuring the characteristic absorption peak intensity at 302nm by using an ultraviolet spectrophotometer, calculating according to Lambert-beer law, and calculating the cumulative drug release percentage at different times according to the measured amount of methotrexate.
f. The pH sensitivity and the near-infrared light responsiveness of the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system are as follows: taking 400mg of the methotrexate/graphene oxide/mesoporous silica/sodium alginate slow release system prepared in the step d, placing the system into a dialysis bag with a molecular interception amount of 3500, then placing the dialysis bag into a phosphate buffer solution with a pH value of 50mL ═ 5.0, irradiating the dialysis bag with near infrared light with a wavelength of 808nm and a power of 1.0W while stirring, taking out 5mL of the solution every 60min during the drug release process, measuring the amount of the released methotrexate, and simultaneously supplementing 5mL of fresh phosphate buffer solution. The concentration of methotrexate is determined by measuring the characteristic absorption peak intensity at 302nm by using an ultraviolet spectrophotometer, calculating according to Lambert-beer law, and calculating the cumulative drug release percentage at different times according to the measured amount of methotrexate.
Further, in the step a, the mass of potassium permanganate added is 5-7 g, the mass of graphite powder added is 0.8-1.2 g, the volume of concentrated sulfuric acid added is 110-130 mL, the volume of phosphoric acid added is 12.2-14.4 mL, and the volume of hydrogen peroxide is 1 mL.
Further, in the step b, the mass of the graphene oxide is 30-50 mg, the mass of the hexadecyl trimethyl ammonium bromide is 0.5-0.7 g, the mass of the sodium hydroxide is 30-50 mg, the mass of the ethyl orthosilicate is 0.8-1.2 g, and the mass of the 3-aminopropyl triethoxysilane is 0.3-0.5 g.
Furthermore, the mass of the graphene oxide/aminated mesoporous silica added in the step c is 280-320 mg, and the concentration of the methotrexate solution is 40-70 μ g/mL.
Further, in the step d, the mass of the sodium alginate is 0.9 to 1.2g, the volume of the phosphate buffer solution is 90 to 120mL, the mass of the 1-ethyl-3-dimethylaminopropyl-carbodiimide hydrochloride is 0.94 to 0.99g, the mass of the N-hydroxysuccinimide is 0.56 to 0.60g, and the mass of the methotrexate/graphene oxide/aminated mesoporous silica is 300 to 340 mg.
The invention has the beneficial effects that: the amino group on the surface of the aminated mesoporous silica and the carboxyl group on the sodium alginate have amidation reaction, so that an amido bond can be generated to coat the sodium alginate on the surface, and the blocking effect on the methotrexate serving as a medicament in mesopores is achieved. Due to the fact that the amido bond has certain pH sensitivity and the graphene oxide has the characteristic of better light-to-heat conversion, the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system with dual responses of pH and near infrared light is obtained, and the purpose of drug controlled release can be achieved through dual stimulation of the near infrared light and the pH.
Drawings
The experiment is further described below with reference to the accompanying drawings.
FIG. 1 is a field emission scanning electron microscope of graphene oxide according to the first embodiment;
FIG. 2 is a scanning electron microscope image of the field emission of methotrexate/graphene oxide/aminated mesoporous silica in the first example;
FIG. 3 is a scanning electron microscope image of field emission of the methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained release system of the first embodiment;
FIG. 4 is a Fourier transform infrared spectrum of graphene oxide, graphene oxide/aminated mesoporous silica, methotrexate/graphene oxide/aminated mesoporous silica of example one;
FIG. 5 is a graph showing the drug release profile of the methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained release system without near infrared light under different pH conditions of example I;
fig. 6 is a graph showing the drug release curves of the methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained-release system under the near-infrared illumination and the near-infrared illumination respectively when the pH is 5.0 in the first example.
Detailed Description
The invention will now be further illustrated by reference to specific examples, which are intended to be illustrative of the invention and are not intended to be a further limitation of the invention.
The first embodiment is as follows:
a preparation method of a drug sustained-release system with pH and near infrared dual responses comprises the following steps:
(1) accurately weighing 6g of potassium permanganate and 1.0g of graphite powder, slowly adding the potassium permanganate and the graphite powder into a mixed solution of 120mL of concentrated sulfuric acid and 13.3mL of phosphoric acid, heating and stirring in a water bath at 50 ℃ for 12 hours, cooling to room temperature, pouring the mixture into an ice water bath containing 1mL of hydrogen peroxide, standing overnight, centrifugally washing a product to remove residual acid, naturally airing and grinding to obtain graphene oxide;
(2) dissolving 40mg of graphene oxide in 50mL of deionized water, performing ultrasonic dispersion for 2h, adding 0.6g of hexadecyl trimethyl ammonium bromide when the graphene oxide solution is completely yellow and no obvious solid can be seen, stirring for 2h at 40 ℃, adding 40mg of sodium hydroxide, continuously stirring for 0.5h, then adding 1.0g of ethyl orthosilicate and 0.4g of 3-aminopropyl triethoxysilane, reacting for 12h, stopping, repeatedly washing and drying with deionized water and ethanol, placing the dried product into a mixed solution of anhydrous ethanol and ammonium nitrate, refluxing for 24h at 60 ℃ to remove a template agent of hexadecyl trimethyl ammonium bromide, repeating for 3 times, repeatedly washing the product with anhydrous ethanol and deionized water, drying at 60 ℃, and grinding to obtain graphene oxide/aminated mesoporous silicon dioxide;
(3) weighing 300mg of graphene oxide/aminated mesoporous silica, adding the graphene oxide/aminated mesoporous silica into 40mL of methotrexate solution with the concentration of 60 mu g/mL, magnetically stirring the mixture for 24 hours, and then carrying out centrifugal separation to obtain methotrexate/graphene oxide/aminated mesoporous silica;
(4) dissolving 1.0g of sodium alginate in a phosphate buffer solution with the pH value of 5.5 and the volume of 100mL, adding 0.96g of 1-ethyl-3-dimethylaminopropyl-carbodiimide hydrochloride and 0.58g of N-hydroxysuccinimide, magnetically stirring at room temperature for 45min, adding 300mg of methotrexate/graphene oxide/aminated mesoporous silica prepared in the step (3) into the sodium alginate solution, magnetically stirring for 12h, placing the obtained dispersion in a petri dish, and freeze-drying at-45 ℃ for 24h to obtain a methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained-release system;
(5) respectively preparing phosphate buffer solutions with pH values of 5.0, 6.8 and 7.4, taking 600mg of the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system prepared in the step (4), placing the system into dialysis bags with molecular interception amount of 3500, respectively placing the dialysis bags into 50mL of phosphate buffer solutions with different pH values, carrying out in-vitro release of the drugs by magnetic stirring at constant temperature of 37 ℃, taking out 5mL of the solution every 60min during the drug release process, measuring the amount of the released methotrexate, and simultaneously supplementing 5mL of fresh phosphate buffer solution. The concentration of methotrexate is determined by measuring the characteristic absorption peak intensity at 302nm by using an ultraviolet spectrophotometer, calculating according to Lambert-beer law, and calculating the cumulative drug release percentage at different times according to the measured amount of methotrexate.
(6) Taking 400mg of the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system prepared in the step (4), placing the system into a dialysis bag with a molecular cutoff of 3500, then placing the dialysis bag into a phosphate buffer solution with a pH value of 50mL and 5.0, irradiating the dialysis bag with near infrared light with a wavelength of 808nm and a power of 1.0W while stirring, taking 5mL of the solution every 60min during the drug release process, measuring the amount of the released methotrexate, and simultaneously supplementing 5mL of fresh phosphate buffer solution. The concentration of methotrexate is determined by measuring the characteristic absorption peak intensity at 302nm by using an ultraviolet spectrophotometer, calculating according to Lambert-beer law, and calculating the cumulative drug release percentage at different times according to the measured amount of methotrexate.
Scanning electron micrographs of the graphene oxide, methotrexate/graphene oxide/aminated mesoporous silica, and methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained-release system prepared in the first example are respectively shown in fig. 1, fig. 2, and fig. 3, and it can be clearly seen from fig. 1 that the graphene oxide exhibits the morphological feature of nano-flake shape. From fig. 2, it can be seen that methotrexate/graphene oxide/aminated mesoporous silica exhibits a coral-like morphology, and its unique cavity structure can be clearly seen. From fig. 3, it can be seen that the methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained release system has a layered stacked structure, and sodium alginate can perfectly coat the system. Fourier transform Infrared Spectroscopy of graphene oxide, graphene oxide/aminated mesoporous silica, methotrexate/graphene oxide/aminated mesoporous silica prepared in example oneFIG. 4 shows the graph with graphene oxide at 1740 and 1650cm-1The absorption peaks at the positions are respectively the characteristic peaks of carbonyl and benzene rings. 1087cm can be clearly seen in the spectrum of graphene oxide/aminated mesoporous silica-1A new characteristic peak appears, which is the characteristic peak of the Si-O-Si bond, and the two absorption peaks of the original graphene oxide are observed to be red-shifted, which is caused by the electrostatic interaction between the graphene oxide and the aminated mesoporous silica, so that the successful preparation of the graphene oxide/aminated mesoporous silica is verified. Methotrexate at 1643 and 1500cm-1The absorption peaks at the position are respectively assigned to-CO-NH group and benzene ring. The spectrum of methotrexate/graphene oxide/aminated mesoporous silica is 1087cm-1The characteristic peaks at (A) are caused by stretching vibration of Si-O-Si, 1643 and 1500cm-1The characteristic peaks in (a) are mainly attributed to the presence of-CO-NH groups and benzene rings in methotrexate. From the results of infrared spectroscopy, it was found that methotrexate was successfully supported on graphene oxide/aminated mesoporous silica.
In the first embodiment, the drug release curve of the methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained-release system at different pH values without near infrared light is shown in fig. 5. As can be seen from the figure, the cumulative drug release percentage of methotrexate has obvious pH sensitivity, and the stronger acidity, the greater the cumulative drug release percentage in the same time, because the acidic condition is favorable for the hydrolysis of amido bonds, thereby leading the shedding of the sodium alginate which is the encapsulating material from the surface of the drug sustained release system and further leading the accelerated release of the drug. Drug release was substantially balanced at 660min, when the cumulative percent release of methotrexate was 72.09%, 43.32%, and 32.46% at pH 5.0, 6.8, and 7.4, respectively. Indicating that acidic conditions are more favorable for the release of methotrexate.
In example one, at a pH of 5.0, the drug release profiles of the methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained release system in the presence and absence of near-infrared light are shown in fig. 6. As can be seen from the figure, the cumulative percentage of drug released by methotrexate has significant near-infrared responsiveness, and under the condition of pH 5.0, the drug is released obviously no matter whether infrared light exists or not, because acidic conditions are favorable for the hydrolysis of amido bonds. However, the cumulative drug release percentage under the near-infrared illumination in the same time is larger, which is mainly due to the fact that the graphene oxide has near-infrared responsiveness, so that near-infrared light can be well converted into heat, and after the near-infrared light is converted into heat, higher temperature can destroy hydrogen bonds between drug molecules and silicon dioxide in mesoporous channels, so that more drugs can be released. The release is basically balanced at 660min, and the cumulative release percentage of the methotrexate is 76.79% and 57.32% under the conditions of near-infrared illumination and no near-infrared illumination. The release of the methotrexate from a methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system is more facilitated under the near-infrared light stimulation condition.
Claims (7)
1. A preparation method of a drug sustained-release system with pH and near infrared dual response is characterized in that: the method comprises the following steps:
a. preparing graphene oxide: slowly adding a certain amount of potassium permanganate and graphite powder into a mixed solution of concentrated sulfuric acid and phosphoric acid, heating and stirring in a water bath at 50 ℃ for 12 hours, cooling to room temperature, pouring into an ice water bath containing hydrogen peroxide, standing overnight, centrifugally washing a product to remove residual acid, naturally airing and grinding to obtain graphene oxide;
b. preparing graphene oxide/aminated mesoporous silica: dissolving the prepared graphene oxide in 50mL of deionized water, performing ultrasonic dispersion for 2h, adding a certain amount of hexadecyl trimethyl ammonium bromide when the graphene oxide solution is completely yellow and no obvious solid can be seen, stirring for 2h at 40 ℃, adding a certain amount of sodium hydroxide, continuously stirring for 0.5h, then adding a certain amount of ethyl orthosilicate and 3-aminopropyl triethoxysilane, stopping after reacting for 12h, repeatedly washing and drying with deionized water and anhydrous ethanol, placing the dried product into a mixed solution of anhydrous ethanol and ammonium nitrate, refluxing for 24h at 60 ℃ to remove a template agent hexadecyl trimethyl ammonium bromide, repeating for 3 times, repeatedly washing the product with anhydrous ethanol and deionized water, drying at 60 ℃, and grinding to obtain graphene oxide/aminated mesoporous silicon dioxide;
c. preparing methotrexate/graphene oxide/aminated mesoporous silica: weighing a certain amount of graphene oxide/aminated mesoporous silica, adding the graphene oxide/aminated mesoporous silica into 40mL of methotrexate solution with a certain concentration, magnetically stirring for 24h, and then carrying out centrifugal separation to obtain methotrexate/graphene oxide/aminated mesoporous silica;
d. preparing a methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system: dissolving a certain amount of sodium alginate in a phosphate buffer solution with the pH value of 5.5, adding a certain amount of 1-ethyl-3-dimethylaminopropyl-carbodiimide hydrochloride and N-hydroxysuccinimide, magnetically stirring for 45min at room temperature, adding the methotrexate/graphene oxide/aminated mesoporous silica prepared in the step c into the sodium alginate solution, magnetically stirring for 12h, placing the obtained dispersion in a watch glass, and freeze-drying for 24h at-45 ℃ to obtain the methotrexate/graphene oxide/mesoporous silica/sodium alginate drug sustained-release system.
2. The method for preparing a drug delivery system with dual pH and nir response of claim 1, wherein: in the step a, the mass of potassium permanganate added is 5-7 g, the mass of graphite powder added is 0.8-1.2 g, the volume of concentrated sulfuric acid added is 110-130 mL, the volume of phosphoric acid added is 12.2-14.4 mL, and the volume of hydrogen peroxide added is 1 mL.
3. The method for preparing a drug delivery system with dual pH and nir response of claim 1, wherein: in the step b, the mass of the graphene oxide is 30-50 mg, the mass of the hexadecyl trimethyl ammonium bromide is 0.5-0.7 g, the mass of the sodium hydroxide is 30-50 mg, the mass of the ethyl orthosilicate is 0.8-1.2 g, and the mass of the 3-aminopropyl triethoxysilane is 0.3-0.5 g.
4. The method for preparing a drug delivery system with dual pH and nir response of claim 1, wherein: the mass of the graphene oxide/aminated mesoporous silica added in the step c is 280-320 mg, and the concentration of the methotrexate solution is 40-70 mu g/mL.
5. The method for preparing a drug delivery system with dual pH and nir response of claim 1, wherein: in the step d, the mass of the sodium alginate is 0.9-1.2 g, the volume of the phosphate buffer solution is 90-120 mL, the mass of the 1-ethyl-3-dimethylaminopropyl-carbodiimide hydrochloride is 0.94-0.99 g, the mass of the N-hydroxysuccinimide is 0.56-0.60 g, and the mass of the methotrexate/graphene oxide/aminated mesoporous silica is 300-340 mg.
6. The drug sustained-release system with pH and near-infrared dual response obtained according to claim 1 is applied to the in-vitro release of drugs under different pH conditions: respectively preparing phosphate buffer solutions with pH values of 5.0, 6.8 and 7.4, taking 600mg of the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system prepared in the step d, placing the system into a dialysis bag with a molecular interception amount of 3500, respectively placing the dialysis bag into 50mL of phosphate buffer solutions with different pH values, carrying out in-vitro release of the drugs by magnetic stirring at constant temperature of 37 ℃, taking out 5mL of the solution every 60min during the drug release process, measuring the amount of the released methotrexate, and simultaneously supplementing 5mL of fresh phosphate buffer solution. The concentration of methotrexate is determined by measuring the characteristic absorption peak intensity at 302nm by using an ultraviolet spectrophotometer, calculating according to Lambert-beer law, and calculating the cumulative drug release percentage at different times according to the measured amount of methotrexate.
7. The drug sustained-release system with pH and near-infrared dual response obtained according to claim 1 is applied to the in-vitro release of drugs under the near-infrared response condition: taking 400mg of the methotrexate/graphene oxide/mesoporous silicon dioxide/sodium alginate drug sustained-release system prepared in the step d, placing the system into a dialysis bag with a molecular interception amount of 3500, then placing the dialysis bag into a phosphate buffer solution with a pH value of 50mL ═ 5.0, irradiating the dialysis bag with near infrared light with a wavelength of 808nm and a power of 1.0W while stirring, taking 5mL of the solution every 60min during the drug release process, measuring the amount of the released methotrexate, and simultaneously supplementing 5mL of fresh phosphate buffer solution. The concentration of methotrexate is determined by measuring the characteristic absorption peak intensity at 302nm by using an ultraviolet spectrophotometer, calculating according to Lambert-beer law, and calculating the cumulative drug release percentage at different times according to the measured amount of methotrexate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010102120.8A CN111214655A (en) | 2020-02-19 | 2020-02-19 | Preparation method of drug sustained-release system with pH and near-infrared dual responses |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010102120.8A CN111214655A (en) | 2020-02-19 | 2020-02-19 | Preparation method of drug sustained-release system with pH and near-infrared dual responses |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111214655A true CN111214655A (en) | 2020-06-02 |
Family
ID=70831311
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010102120.8A Pending CN111214655A (en) | 2020-02-19 | 2020-02-19 | Preparation method of drug sustained-release system with pH and near-infrared dual responses |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111214655A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112569367A (en) * | 2020-12-15 | 2021-03-30 | 安徽工程大学 | 5-fluorouracil-mesoporous silica-sodium alginate drug delivery system and preparation method thereof |
| CN113995836A (en) * | 2021-10-22 | 2022-02-01 | 常州大学 | Multi-response drug controlled release system, preparation method and application |
| CN114652841A (en) * | 2022-03-11 | 2022-06-24 | 常州大学 | Double-drug-loading system with pH, redox and near-infrared triple responses, and preparation method and application thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963717A (en) * | 2016-05-31 | 2016-09-28 | 电子科技大学 | Composite nano-drug for integrated tumor diagnosis and treatment and preparation method thereof |
| WO2017041033A1 (en) * | 2015-09-04 | 2017-03-09 | Brinker C Jeffrey | Mesoporous silica nanoparticles and supported lipid bi-layer nanoparticles for biomedical applications |
| CN106974882A (en) * | 2017-03-07 | 2017-07-25 | 常州大学 | A kind of polypyrrole/mesoporous silicon oxide of core shell structure/application of the graphene quantum dot nano composite material in medicine controlled releasing |
| US20200038525A1 (en) * | 2018-08-06 | 2020-02-06 | Imam Abdulrahman Bin Faisal University | Curcumin-based magnetic nanostructured system for dual response of imaging and therapeutics |
-
2020
- 2020-02-19 CN CN202010102120.8A patent/CN111214655A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017041033A1 (en) * | 2015-09-04 | 2017-03-09 | Brinker C Jeffrey | Mesoporous silica nanoparticles and supported lipid bi-layer nanoparticles for biomedical applications |
| CN105963717A (en) * | 2016-05-31 | 2016-09-28 | 电子科技大学 | Composite nano-drug for integrated tumor diagnosis and treatment and preparation method thereof |
| CN106974882A (en) * | 2017-03-07 | 2017-07-25 | 常州大学 | A kind of polypyrrole/mesoporous silicon oxide of core shell structure/application of the graphene quantum dot nano composite material in medicine controlled releasing |
| US20200038525A1 (en) * | 2018-08-06 | 2020-02-06 | Imam Abdulrahman Bin Faisal University | Curcumin-based magnetic nanostructured system for dual response of imaging and therapeutics |
Non-Patent Citations (4)
| Title |
|---|
| YI WANG，ET AL.: "Multifunctional Mesoporous Silica-Coated Graphene Nanosheet Used for Chemo-Photothermal Synergistic Targeted Therapy of Glioma", 《J. AM. CHEM. SOC.》 * |
| 向思琪等: "pH响应海藻酸@介孔二氧化硅/阿霉素纳米粒子的制备及应用研究", 《中国新药杂志》 * |
| 王稼祎: "基于氧化石墨烯和介孔二氧化硅的纳米药物载体的特性研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
| 荆洁颖著: "《高分散纳米催化剂制备及光催化应用》", 30 September 2017, 北京：冶金工业出版社 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112569367A (en) * | 2020-12-15 | 2021-03-30 | 安徽工程大学 | 5-fluorouracil-mesoporous silica-sodium alginate drug delivery system and preparation method thereof |
| CN112569367B (en) * | 2020-12-15 | 2022-08-23 | 安徽工程大学 | 5-fluorouracil-mesoporous silica-sodium alginate drug delivery system and preparation method thereof |
| CN113995836A (en) * | 2021-10-22 | 2022-02-01 | 常州大学 | Multi-response drug controlled release system, preparation method and application |
| CN114652841A (en) * | 2022-03-11 | 2022-06-24 | 常州大学 | Double-drug-loading system with pH, redox and near-infrared triple responses, and preparation method and application thereof |
| CN114652841B (en) * | 2022-03-11 | 2024-03-19 | 常州大学 | pH, redox and near infrared triple-response type dual-drug-carrying system and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111214655A (en) | Preparation method of drug sustained-release system with pH and near-infrared dual responses | |
| Chen et al. | Graphitic carbon nitride nanosheet@ metal–organic framework core–shell nanoparticles for photo-chemo combination therapy | |
| Shi et al. | Facile synthesis of polymeric fluorescent organic nanoparticles based on the self-polymerization of dopamine for biological imaging | |
| Zhou et al. | Light-responsive polymersomes with a charge-switch for targeted drug delivery | |
| Xu et al. | Group IV nanodots: synthesis, surface engineering and application in bioimaging and biotherapy | |
| CN106267204B (en) | A kind of composite material and preparation method and application of black phosphorus nanometer sheet-antitumoral compounds | |
| Ho et al. | The pH-controlled nanoparticles size of polydopamine for anti-cancer drug delivery | |
| Du et al. | Multicolor nitrogen-doped carbon dots for live cell imaging | |
| KR100475988B1 (en) | Method for producing a coenzyme q10/gamma-cyclodextrin complex | |
| Gui et al. | Embedding fluorescent mesoporous silica nanoparticles into biocompatible nanogels for tumor cell imaging and thermo/pH-sensitive in vitro drug release | |
| Wang et al. | Facile surface functionalization of upconversion nanoparticles with phosphoryl pillar [5] arenes for controlled cargo release and cell imaging | |
| Kim et al. | Synthesis of conjugated polymer nanoparticles with core-shell structure for cell imaging and photodynamic cancer therapy | |
| Mazrad et al. | Target-specific induced hyaluronic acid decorated silica fluorescent nanoparticles@ polyaniline for bio-imaging guided near-infrared photothermal therapy | |
| CN114652841B (en) | pH, redox and near infrared triple-response type dual-drug-carrying system and preparation method and application thereof | |
| Gwak et al. | Efficient doxorubicin delivery using deaggregated and carboxylated nanodiamonds for cancer cell therapy | |
| CN111329877A (en) | Mesoporous silica-based active oxygen material with dual responses to tumor microenvironment and preparation method thereof | |
| Qin et al. | Multi-responsive drug delivery nanoplatform for tumor-targeted synergistic photothermal/dynamic therapy and chemotherapy | |
| Qin et al. | Fe 3 O 4@ SiO 2 mesoporous spheres as Fe (ii) donors loaded with artemisinin and a photosensitizer to alleviate tumor hypoxia in PDT for enhanced anticancer therapy | |
| Chen et al. | Chemo-photothermal effects of doxorubicin/silica–carbon hollow spheres on liver cancer | |
| CN106806906B (en) | Preparation method of rare earth up-conversion nano-drug carrier integrating fluorescence imaging and drug loading | |
| CN107281220B (en) | Mesoporous silica-based active oxygen (ROS) radiotherapy sensitizer and preparation method thereof | |
| CN112625254B (en) | Surface-modifiable pH-responsive hollow covalent organic framework nanosphere and synthesis method thereof | |
| Shi et al. | Fabrication of rod-like nanocapsules based on polylactide and 3, 4-dihydroxyphenylalanine for a drug delivery system | |
| CN112704661A (en) | Drug-loaded fluorescent nanocellulose hydrogel and preparation method and application thereof | |
| CN106913872A (en) | Adriamycin and NO donor nano composite materials and preparation method 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 | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20200602 |
|
| WD01 | Invention patent application deemed withdrawn after publication |