CN106492221A - A kind of reduction responsive nano graphene oxide cladding carries medicine mesoporous silicon dioxide nano particle and preparation method thereof - Google Patents
A kind of reduction responsive nano graphene oxide cladding carries medicine mesoporous silicon dioxide nano particle and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- 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
Abstract
The present invention relates to a kind of reduction responsive nano graphene oxide cladding carries medicine mesoporous silicon dioxide nano particle and preparation method thereof, which is made up of the mesoporous silicon dioxide nano particle of compound-modified the loaded medicine simultaneously containing disulfide bond, amino and carboxyl nano graphene oxide that is sub and coating above-mentioned mesoporous silicon dioxide nano particle.Preparation method is by while mesoporous silicon dioxide nano particle of compound-modified the loaded medicine containing disulfide bond, amino and carboxyl is added in the nano graphene oxide aqueous solution by activated carboxylic, under room temperature there is acid amides reaction in stirring, centrifuge washing, freeze-drying obtain nano graphene oxide modification with reduction response medicine controlled release material.Carrier material good biocompatibility of the present invention, drugloading rate are high, can realize the controlled release of medicine using the reduction response of disulfide bond；Medicine is hardly discharged around normal cell, and quick release under tumour cell reproducibility microenvironment, with important physiological significance and researching value.
Description
Technical field
The present invention relates to a kind of carry medicine controlled-release material and preparation method thereof, and in particular to a kind of reduction responsive nano oxidation
Graphene coated carries medicine mesoporous silicon dioxide nano particle and preparation method thereof.
Background technology
At present, malignant tumour has become the killer of harm human health, and its incidence of disease is risen year by year, and presents youth
The situation of change.For malignant tumour, main treatment means are exactly chemotherapy, operation and radiotherapy.At present, chemotherapy becomes the most frequently used treatment
Method, but as the drug dose of chemotherapy is larger, and certain harm can also be produced to normal cell, the curative effect of chemotherapy is relatively low.
Nanometer technology is widely used in medical domain, especially in anticancer at present as a kind of emerging science and technology
The aspect such as the exploitation for the treatment of means and the preparation of nano-medicament carrier, has played extremely important effect.Nano particle is in medicine
There is in terms of conveying the unrivaled superiority of other systems：Which can effectively improve drug effect, mitigate toxic and side effect, improve
Blood concentration and the stability of medicine；The controlled release of medicine can also be realized, the greatest treatment efficacy of medicine is played；Difficulty can also be improved
The dissolution rate of soluble drug and absorptivity；And realize targeted drug delivery.
Preferably medicine controlled releasing behavior is closely bound up with the selection of pharmaceutical carrier.Mesoporous silicon oxide has regular, orderly
Duct, good biocompatibility and degradability are widely used in intellectual drug control delivery recently.Scientific research scholar elder generation
After work out：By the modification of poly- 2- (lignocaine) ethyl methacrylate to the mesoporous place of mesoporous silicon oxide, prepare and have
The controlled drug delivery systems of pH responses；Thermosensitive polymer PNIPAM is incorporated into be formed in mesoporous silicon there is temperature
The organic inorganic hybridization system of degree response；By the opening of the channel with optically active cumarin modification to mesoporous silicon oxide,
The first the mesoporous silicon controlled release system with photoresponse creatively have developed；And " a top has been invented for liver esterase
Portion controls " system, according to the controllability release that the enzyme for adding carries out medicine.
Nano graphene oxide has larger specific surface area and good biocompatibility, can be used as bio-medical material
Material.Someone is covered to mesoporous silicon oxide by acetal bonds using graphene quantum dot, is prepared with pH responses
Medicine-carried system；Somebody has prepared the medicine-carried system with optical Response, by using nano graphene oxide to mesoporous two
Silicon oxide nanoparticle is encapsulated.But regrettably, so far still without using nano graphene oxide and mesoporous silicon oxide
Nano-particle combines the relevant report of the controlled drug delivery systems for preparing reduction response.
Content of the invention
The purpose of the present invention is that for above-mentioned the deficiencies in the prior art, there is provided a kind of reduction responsive nano oxidation stone
Black alkene cladding carries medicine mesoporous silicon dioxide nano particle.It is a further object of the present invention to provide a kind of reduction responsive nano oxygen
Graphite alkene cladding carries the preparation method of medicine mesoporous silicon dioxide nano particle.
The purpose of the present invention is achieved through the following technical solutions：
The coating mesoporous silica medicine-carried controlled release nanometer material of one kind reduction responsive nano graphene oxide, is by two sulphur
The nano oxygen fossil of the sub and coating mesoporous Nano particles of silicon dioxide of the mesoporous silicon dioxide nano particle of key, amino and carboxyl modified
Black alkene composition, described mesoporous silicon dioxide nano particle can load medicine, and the particle diameter of mesoporous silicon dioxide nano particle is
50-200nm, mesoporous pore size are 1.5-5.0nm.
The size of described nano graphene oxide is 3-100nm.
Described medicine is water-soluble or oil-soluble medicine.
Described water soluble drug is vitamin C, adriamycin or mitomycin.
The oil-soluble medicine is brufen, taxol, camptothecine, lomustine or ginsenoside.
Above-mentioned reduction responsive nano graphene oxide cladding carries the preparation method of medicine mesoporous silicon dioxide nano particle, bag
Include following steps：
A. the mesoporous silicon oxide for being possible to load medicine is reacted with silane coupler, in its surface grafting amino, is obtained
Amination mesoporous silicon oxide；
B. will be anti-with the compound simultaneously containing disulfide bond, amino and carboxyl for step A gained amination mesoporous silicon oxide
Should, surface grafting disulfide bond is obtained the mesoporous silicon oxide containing disulfide bond；
C., step B gained is contained the method for the mesoporous silicon oxide by physical impregnation of disulfide bond, Jie for carrying medicine is formed
Hole silica；
D. step C gained is carried the amino on the mesoporous silicon oxide after medicine to enter with the carboxyl on nano graphene oxide surface
Row acid amides reacts, and obtains load medicine mesoporous silicon dioxide nano particle for reducing responsive nano graphene oxide cladding.
Above-mentioned reduction responsive nano graphene oxide cladding carries the preparation method of medicine mesoporous silicon dioxide nano particle, tool
Body is comprised the following steps：
A. by 0.1g particle diameters be 50-200nm, mesoporous pore size for 1.5-5.0nm mesoporous silicon dioxide nano particle
(MSNs) ultrasonic disperse in the distilled water of 10ml is subsequently added the acetic acid and 25 μ l silane couplers of 100 μ l, stirs under room temperature
Mix 24 hours, centrifuge washing, obtain amination mesoporous silicon dioxide nano particle (MSNs-NH2)；
B. the compound for containing disulfide bond, amino and carboxyl while by 0.01g is scattered in the PBS cushioning liquid of 10ml
(pH=5.0), the aqueous solution of 1- (3- the dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides of 50-100mg is added afterwards,
After stirring 1 hour under room temperature, by 0.04gMSNs-NH2It is added in above-mentioned solution, stirs 24 hours under room temperature, centrifuge washing,
Obtain the son (MSNs-SS-NH of the mesoporous silicon dioxide nano particle containing disulfide bond2)；
C. drug molecule is diffused into by MSNs-SS-NH using physical impregnation method2Mesopore orbit, then by MSNs-SS-NH2Point
It is scattered in the ethanol solution containing medicine, is stirred at room temperature 24 hours under dark environment, centrifuge washing obtains being loaded with medicine
MSNs-SS-NH2；
D. 1- (the 3- of 10mg, by the nano graphene oxide ultrasonic disperse of 10mg in the distilled water of 10ml, are added afterwards
Dimethylamino-propyl) -3- ethyl-carbodiimide hydrochlorides the aqueous solution, under room temperature stir 1 hour；20mg is loaded with medicine again
MSNs-SS-NH2It is added in above-mentioned mixed liquor, stirs 24 hours under room temperature, centrifuge washing obtains nano graphene oxide
(GO) mesoporous silicon dioxide nano particle for being loaded with medicine for coating.
Described silane coupler is gamma-aminopropyl-triethoxy-silane, γ-aminopropyltrimethoxysilane, 2- ammonia second
Base aminopropyl trimethoxysilane, N- β (aminoethyl)-γ-aminopropyltrimethoxysilane or N- β (aminoethyl)-γ-aminopropyl
Methyl dimethoxysilane.
The compound for containing disulfide bond, amino and carboxyl while described is oxidized form of glutathione or cystine.
Compared with prior art, the beneficial effects of the present invention is：
1. using the high nano graphene oxide of biocompatibility and mesoporous silicon dioxide nano particle, made product life
Thing compatibility is stronger.
2. by the concentration of the particle size, pore size and drug solution of regulation mesoporous silicon dioxide nano particle,
Can effective regulating drug useful load.
3. chemical modification process only needs simple whipping process to can achieve effective cladding of nano graphene oxide, operation
Simply, conveniently.
4. the drug release material prepared by contains disulfide bond, with reduction response, it is possible to achieve medicine is thin in tumour
Quick reduction response release at born of the same parents and " zero release " at the normal cell.
Specific embodiment
The coating mesoporous silica medicine-carried controlled release nanometer material of one kind reduction responsive nano graphene oxide, is by two sulphur
The nano oxygen fossil of the sub and coating mesoporous Nano particles of silicon dioxide of the mesoporous silicon dioxide nano particle of key, amino and carboxyl modified
Black alkene composition, described mesoporous silicon dioxide nano particle can load medicine, and the particle diameter of mesoporous silicon dioxide nano particle is
50-200nm, mesoporous pore size are 1.5-5.0nm.
The size of described nano graphene oxide is 3-100nm.
Described medicine is water-soluble or oil-soluble medicine.
Described water soluble drug is vitamin C, adriamycin or mitomycin.
The oil-soluble medicine is brufen, taxol, camptothecine, lomustine or ginsenoside.
Above-mentioned reduction responsive nano graphene oxide cladding carries the preparation method of medicine mesoporous silicon dioxide nano particle, bag
Include following steps：
A. the mesoporous silicon oxide for being possible to load medicine is reacted with silane coupler, in its surface grafting amino, is obtained
Amination mesoporous silicon oxide；
B. will be anti-with the compound simultaneously containing disulfide bond, amino and carboxyl for step A gained amination mesoporous silicon oxide
Should, surface grafting disulfide bond is obtained the mesoporous silicon oxide containing disulfide bond；
C., step B gained is contained the method for the mesoporous silicon oxide by physical impregnation of disulfide bond, Jie for carrying medicine is formed
Hole silica；
D. step C gained is carried the amino on the mesoporous silicon oxide after medicine to enter with the carboxyl on nano graphene oxide surface
Row acid amides reacts, and obtains load medicine mesoporous silicon dioxide nano particle for reducing responsive nano graphene oxide cladding.
Embodiment 1
A. by 0.1g particle diameters be 100nm, mesoporous pore size for 3nm mesoporous silicon dioxide nano particle (MSNs) ultrasonic disperse
To in the distilled water of 10ml, the gamma-aminopropyl-triethoxy-silane of the acetic acid and 25 μ l of 100 μ l is subsequently added, is stirred under room temperature
24 hours, centrifuge washing obtained amination mesoporous silicon dioxide nano particle (MSNs-NH2)；
B. the oxidized form of glutathione of 0.01g is scattered in (pH=5.0) in the PBS cushioning liquid of 10ml, is added afterwards
The aqueous solution of 1- (3- the dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides of 50mg, stirs 1 hour to activate under room temperature
Carboxyl on oxidized form of glutathione；By 0.04gMSNs-NH2It is added in above-mentioned solution, stirs 24 hours under room temperature, centrifugation
Washing, obtains the son (MSNs-SS-NH of the mesoporous silicon dioxide nano particle containing disulfide bond2)；
C. camptothecin molecule is diffused into by MSNs-SS-NH using the method for simple physical impregnation2Mesopore orbit；Again will
MSNs-SS-NH2It is distributed in the ethanol solution containing camptothecine, is stirred at room temperature 24 hours under dark environment, centrifuge washing,
Obtain the MSNs-SS-NH for being loaded with camptothecine2(CPT@MSNs-SS-NH2)；
D. the 1- of 10mg, by the 10nm nano graphene oxides ultrasonic disperse of 10mg in the distilled water of 10ml, is added afterwards
The aqueous solution of (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, under room temperature stir 1 hour nano oxidized to activate
The carboxyl of graphenic surface；CPT@MSNs-SS-NH by 20mg2It is added in above-mentioned mixed liquor, stirs 24 hours under room temperature,
Centrifuge washing, obtains mesoporous silicon dioxide nano particle (the CPT@MSNs- for being loaded with CPT that nano graphene oxide (GO) is coated
SS-GO).
Embodiment 2
A. by 0.1g particle diameters be 150nm, mesoporous pore size for 5nm mesoporous silicon dioxide nano particle (MSNs) ultrasonic disperse
To in the distilled water of 10ml, the γ-aminopropyltrimethoxysilane of the acetic acid and 25 μ l of 100 μ l is subsequently added, is stirred under room temperature
24 hours, centrifuge washing obtained amination mesoporous silicon dioxide nano particle (MSNs-NH2)；
B. 0.01g cystines are scattered in (pH=5.0) in the PBS cushioning liquid of 10ml, add the 1- (3- of 50mg afterwards
Dimethylamino-propyl) -3- ethyl-carbodiimide hydrochlorides the aqueous solution, under room temperature stir 1 hour so as to activation cystine on
Carboxyl；By 0.04gMSNs-NH2It is added in above-mentioned solution, stirs 24 hours under room temperature, centrifuge washing is obtained containing disulfide bond
Mesoporous silicon dioxide nano particle (MSNs-SS-NH2)；
C. Doxorubicin molecules are diffused into by MSNs-SS-NH using the method for simple physical impregnation2Mesopore orbit；Again will
MSNs-SS-NH2It is distributed in the aqueous solution containing adriamycin, is stirred at room temperature 24 hours under dark environment, centrifuge washing is obtained
To the MSNs-SS-NH for being mounted with adriamycin2(DOX@MSNs-SS-NH2)；
D., by the 100nm nano graphene oxides ultrasonic disperse of 10mg in the distilled water of 10ml, add 10mg's afterwards
The aqueous solution of 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, stirs 1 hour so as to activation nano oxygen under room temperature
The carboxyl on graphite alkene surface；DOX@MSNs-SS-NH by 20mg2It is added in above-mentioned mixed liquor, under room temperature, stirring 24 is little
When, centrifuge washing obtains mesoporous silicon oxide (the DOX@MSNs-SS- for being loaded with DOX that nano graphene oxide (GO) is coated
GO).
Embodiment 3
A. by 0.1g particle diameters be 50nm, mesoporous pore size for 1.5nm mesoporous silicon dioxide nano particle (MSNs) ultrasound point
It is scattered in the distilled water of 10ml, is subsequently added the 2- aminoethylaminopropyl trimethoxy silanes of the acetic acid and 25 μ l of 100 μ l, room temperature
Lower stirring 24 hours, centrifuge washing obtains amination mesoporous silicon dioxide nano particle (MSNs-NH2)；
B. 0.01g oxidizeds form of glutathione are scattered in (pH=5.0) in the PBS cushioning liquid of 10ml, are added afterwards
The aqueous solution of 1- (3- the dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides of 100mg, stirs 1 hour to live under room temperature
Change the carboxyl on oxidized form of glutathione；By 0.04gMSNs-NH2It is added in above-mentioned solution, stirs 24 hours under room temperature, from
The heart is washed, and obtains the son (MSNs-SS-NH of the mesoporous silicon dioxide nano particle containing disulfide bond2)；
C. ibuprofen molecule is diffused into by MSNs-SS-NH using the method for simple physical impregnation2Mesopore orbit；Again will
MSNs-SS-NH2It is distributed in the ethanol solution containing brufen, stirs 24 hours under room temperature condition, centrifuge washing is filled
The MSNs-SS-NH of brufen is carried2(IBU@MSNs-SS-NH2)；
D. the 1- of 10mg, by the 3nm nano graphene oxides ultrasonic disperse of 10mg in the distilled water of 10ml, is added afterwards
The aqueous solution of (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, under room temperature stir 1 hour nano oxidized to activate
The carboxyl of graphenic surface；IBU@MSNs-SS-NH by 20mg2It is added in above-mentioned mixed liquor, stirs 24 hours under room temperature,
Centrifuge washing, obtains the mesoporous silicon oxide (IBU@MSNs-SS-GO) for being loaded with IBU that nano graphene oxide (GO) is coated.
Embodiment 4
A. by 0.1g particle diameters be 200nm, mesoporous pore size for 3nm mesoporous silicon dioxide nano particle (MSNs) ultrasonic disperse
To in the distilled water of 10ml, N- β (aminoethyl)-γ-aminopropyl trimethoxy silicon of the acetic acid and 25 μ l of 100 μ l is subsequently added
Alkane, stirs 24 hours under room temperature, and centrifuge washing obtains amination mesoporous silicon dioxide nano particle (MSNs-NH2)；
B. 0.01g cystines are scattered in (pH=5.0) in the PBS cushioning liquid of 10ml, add the 1- (3- of 50mg afterwards
Dimethylamino-propyl) -3- ethyl-carbodiimide hydrochlorides the aqueous solution, under room temperature stir 1 hour so as to activation cystine on
Carboxyl；By 0.04gMSNs-NH2It is added in above-mentioned solution, stirs 24 hours under room temperature, centrifuge washing is obtained containing disulfide bond
Mesoporous silicon dioxide nano particle (MSNs-SS-NH2)；
C. vitamin C molecules are diffused into by MSNs-SS-NH using the method for simple physical impregnation2Mesopore orbit；Again will
MSNs-SS-NH2In being distributed to containing the ascorbic aqueous solution, stir 24 hours under room temperature condition, centrifuge washing is loaded
Ascorbic MSNs-SS-NH2(VC@MSNs-SS-NH2)；
D. the 1- of 10mg, by the 50nm nano graphene oxides ultrasonic disperse of 10mg in the distilled water of 10ml, is added afterwards
The aqueous solution of (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, under room temperature stir 1 hour nano oxidized to activate
The carboxyl of graphenic surface；VC@MSNs-SS-NH by 20mg2It is added in above-mentioned mixed liquor, stirs 24 hours under room temperature, from
The heart is washed, and obtains the mesoporous silicon oxide (VC@MSNs-SS-GO) for being loaded with VC that nano graphene oxide (GO) is coated.
Embodiment 5
A. by 0.1g particle diameters be 200nm, mesoporous pore size for 3nm mesoporous silicon dioxide nano particle (MSNs) ultrasonic disperse
To in the distilled water of 10ml, N- β (aminoethyl)-γ-aminopropyltriethoxy dimethoxy of the acetic acid and 25 μ l of 100 μ l is subsequently added
Silane, stirs 24 hours under room temperature, and centrifuge washing obtains amination mesoporous silicon dioxide nano particle (MSNs-NH2)；
B. 0.01g oxidizeds form of glutathione are scattered in (pH=5.0) in the PBS cushioning liquid of 10ml, are added afterwards
The aqueous solution of 1- (3- the dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides of 100mg, stirs 1 hour to live under room temperature
Change the carboxyl on oxidized form of glutathione；By 0.04gMSNs-NH2It is added in above-mentioned solution, stirs 24 hours under room temperature, from
The heart is washed, and obtains the son (MSNs-SS-NH of the mesoporous silicon dioxide nano particle containing disulfide bond2)；
C. taxane molecule is diffused into by MSNs-SS-NH using the method for simple physical impregnation2Mesopore orbit.Will
MSNs-SS-NH2It is distributed in the dimethyl sulphoxide solution containing taxol, stirs 24 hours under room temperature condition, centrifuge washing,
Obtain the MSNs-SS-NH for being loaded with taxol2(Tax@MSNs-SS-NH2)；
D. the 1- of 10mg, by the 20nm nano graphene oxides ultrasonic disperse of 10mg in the distilled water of 10ml, is added afterwards
The aqueous solution of (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, under room temperature stir 1 hour nano oxidized to activate
The carboxyl of graphenic surface；Tax@MSNs-SS-NH by 20mg2It is added in above-mentioned mixed liquor, stirs 24 hours under room temperature,
Centrifuge washing, obtains the mesoporous silicon oxide (Tax@MSNs-SS-GO) for being loaded with Tax that nano graphene oxide (GO) is coated.
Embodiment 6
A. by 0.1g particle diameters be 200nm, mesoporous pore size for 3nm mesoporous silicon dioxide nano particle (MSNs) ultrasonic disperse
To in the distilled water of 10ml, N- β (aminoethyl)-γ-aminopropyltriethoxy dimethoxy of the acetic acid and 25 μ l of 100 μ l is subsequently added
Silane, stirs 24 hours under room temperature, and centrifuge washing obtains amination mesoporous silicon dioxide nano particle (MSNs-NH2)；
B. 0.01g oxidizeds form of glutathione are scattered in (pH=5.0) in the PBS cushioning liquid of 10ml, are added afterwards
The aqueous solution of 1- (3- the dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides of 100mg, stirs 1 hour to live under room temperature
Change the carboxyl on oxidized form of glutathione；By 0.04gMSNs-NH2It is added in above-mentioned solution, stirs 24 hours under room temperature, from
The heart is washed, and obtains the son (MSNs-SS-NH of the mesoporous silicon dioxide nano particle containing disulfide bond2)；
C. camptothecin molecule is diffused into by MSNs-SS-NH using the method for simple physical impregnation2Mesopore orbit.Will
MSNs-SS-NH2It is distributed in the ethanol solution containing camptothecine, is stirred at room temperature 24 hours under dark environment, centrifuge washing,
Obtain the MSNs-SS-NH for being loaded with camptothecine2(CPT@MSNs-SS-NH2)；
D. the 1- of 10mg, by the 10nm nano graphene oxides ultrasonic disperse of 10mg in the distilled water of 10ml, is added afterwards
The aqueous solution of (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides, under room temperature stir 1 hour nano oxidized to activate
The carboxyl of graphenic surface；CPT@MSNs-SS-NH by 20mg2It is added in above-mentioned mixed liquor, stirs 24 hours under room temperature,
Centrifuge washing, obtains mesoporous silicon dioxide nano particle (the CPT@MSNs- for being loaded with CPT that nano graphene oxide (GO) is coated
SS-GO).
Claims (9)
1. a kind of reduction responsive nano graphene oxide cladding carries medicine mesoporous silicon dioxide nano particle, it is characterised in that：It is
Nanometer by the sub and coating mesoporous Nano particles of silicon dioxide of the mesoporous silicon dioxide nano particle of disulfide bond, amino and carboxyl modified
Graphene oxide is constituted, and described mesoporous silicon dioxide nano particle can load medicine, mesoporous silicon dioxide nano particle
Particle diameter is 50-200nm, and mesoporous pore size is 1.5-5.0nm.
2. a kind of reduction responsive nano graphene oxide cladding according to claim 1 carries medicine mesoporous silicon dioxide nano
Particle, it is characterised in that：The size of described nano graphene oxide is 3-100nm.
3. a kind of reduction responsive nano graphene oxide cladding according to claim 1 carries medicine mesoporous silicon dioxide nano
Particle, it is characterised in that：Described medicine is water-soluble or oil-soluble medicine.
4. a kind of reduction responsive nano graphene oxide cladding according to claim 3 carries medicine mesoporous silicon dioxide nano
Particle, it is characterised in that：Described water soluble drug is vitamin C, adriamycin or mitomycin.
5. a kind of reduction responsive nano graphene oxide cladding according to claim 3 carries medicine mesoporous silicon dioxide nano
Particle, it is characterised in that：The oil-soluble medicine is brufen, taxol, camptothecine, lomustine or ginsenoside.
6. a kind of reduction responsive nano graphene oxide cladding as claimed in claim 1 carries medicine mesoporous silicon dioxide nano particle
The preparation method of son, it is characterised in that comprise the following steps：
A. the mesoporous silicon oxide for being possible to load medicine is reacted with silane coupler, in its surface grafting amino, amino is obtained
Change mesoporous silicon oxide；
B. by step A gained amination mesoporous silicon oxide and the reaction of the compound containing disulfide bond, amino and carboxyl simultaneously, table
Face is grafted disulfide bond, and the mesoporous silicon oxide containing disulfide bond is obtained；
C., step B gained is contained the method for the mesoporous silicon oxide by physical impregnation of disulfide bond, is formed and is carried mesoporous the two of medicine
Silica；
D. the amino carried step C gained on the mesoporous silicon oxide after medicine carries out acyl with the carboxyl on nano graphene oxide surface
Amine reacts, and obtains load medicine mesoporous silicon dioxide nano particle for reducing responsive nano graphene oxide cladding.
7. a kind of reduction responsive nano graphene oxide cladding according to claim 6 carries medicine mesoporous silicon dioxide nano
The preparation method of particle, it is characterised in that specifically include following steps：
A. by 0.1g particle diameters be 50-200nm, mesoporous pore size for 1.5-5.0nm mesoporous silicon dioxide nano particle (MSNs) surpass
Sound is distributed in the distilled water of 10ml, is subsequently added the acetic acid and 25 μ l silane couplers of 100 μ l, and under room temperature, stirring 24 is little
When, centrifuge washing obtains amination mesoporous silicon dioxide nano particle (MSNs-NH2)；
B. the compound for containing disulfide bond, amino and carboxyl while by 0.01g is scattered in (pH in the PBS cushioning liquid of 10ml
=5.0), afterwards add 50-100mg 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides the aqueous solution, room temperature
After lower stirring 1 hour, by 0.04gMSNs-NH2It is added in above-mentioned solution, stirs 24 hours under room temperature, centrifuge washing is obtained
Mesoporous silicon dioxide nano particle containing disulfide bond (MSNs-SS-NH2)；
C. drug molecule is diffused into by MSNs-SS-NH using physical impregnation method2Mesopore orbit, then by MSNs-SS-NH2It is distributed to
In ethanol solution containing medicine, it is stirred at room temperature 24 hours under dark environment, centrifuge washing obtains being loaded with medicine
MSNs-SS-NH2；
D. 1- (the 3- diformazans of 10mg, by the nano graphene oxide ultrasonic disperse of 10mg in the distilled water of 10ml, are added afterwards
Aminopropyl) -3- ethyl-carbodiimide hydrochlorides the aqueous solution, under room temperature stir 1 hour；20mg is loaded with medicine again
MSNs-SS-NH2It is added in above-mentioned mixed liquor, stirs 24 hours under room temperature, centrifuge washing obtains nano graphene oxide
(GO) mesoporous silicon dioxide nano particle for being loaded with medicine for coating.
8. a kind of reduction responsive nano graphene oxide cladding according to claim 6 carries medicine mesoporous silicon dioxide nano
The preparation method of particle, it is characterised in that：Described silane coupler is gamma-aminopropyl-triethoxy-silane, γ-aminopropyl three
Methoxy silane, 2- aminoethylaminopropyl trimethoxy silanes, N- β (aminoethyl)-γ-aminopropyltrimethoxysilane or N- β
(aminoethyl)-γ-aminopropyltriethoxy dimethoxysilane.
9. a kind of reduction responsive nano graphene oxide cladding according to claim 6 carries medicine mesoporous silicon dioxide nano
The preparation method of particle, it is characterised in that：The compound for containing disulfide bond, amino and carboxyl while described is oxidized form paddy Guang
Sweet peptide or cystine.
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| CN109432053A (en) * | 2018-10-31 | 2019-03-08 | 湖北大学 | A kind of magnetic mesoporous silicon nano controlled drug delivery system of pH response type and preparation method thereof |
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