CN110200944A - A kind of pH/ temperature sensitivity double-response type nano-medicament carrier and its preparation and application - Google Patents
A kind of pH/ temperature sensitivity double-response type nano-medicament carrier and its preparation and application Download PDFInfo
- Publication number
- CN110200944A CN110200944A CN201910635085.3A CN201910635085A CN110200944A CN 110200944 A CN110200944 A CN 110200944A CN 201910635085 A CN201910635085 A CN 201910635085A CN 110200944 A CN110200944 A CN 110200944A
- Authority
- CN
- China
- Prior art keywords
- temperature sensitivity
- mesoporous silicon
- silicon dioxide
- response type
- nano particle
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—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
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a kind of pH/ temperature sensitivity double-response type nano-medicament carrier and its preparation and application, which is the block copolymer in the mesoporous silicon dioxide nano particle sublist face of amino functional by hydrogen bond action package with pH/ temperature sensitivity；Present invention composite nanoparticle obtained can be used as hydrophobic drug carrier and apply in medicine sustained and controlled release system.Composite nanoparticle of the invention has preferable dispersibility, more uniform size and adjustable particle size, and preferable pH/ temperature sensitivity is shown in medicine sustained and controlled release system, therefore the nano-medicament carrier therapeutic field of tumor with good application prospect.
Description
Technical field
The present invention relates to nano-medicament carrier material fields, and in particular to a kind of pH/ temperature sensitivity double-response type is received
Rice pharmaceutical carrier and its preparation and application.
Background technique
Mesoporous silicon dioxide nano particle has high-specific surface area, macropore appearance, morphology controllable, good thermal stability and life
The advantages that object is compatible, while surface silicone hydroxyl abundant provides reactivity site, makes its easy functionalization, passes through Different Strategies
It can prepare with multi-functional inorganic-organic mesoporous silicon oxide composite nano materials, mesoporous silicon dioxide nano composite material
Synthesis and its application in medicine sustained and controlled release have become the hot spot of research, especially there is the dual sound of pH/ temperature sensitivity
The mesoporous material for answering type has broad application prospects in terms of medicine sustained and controlled release as nano-medicament carrier.
Functional macromolecule polymer has good biocompatibility, under extraneous micro-environmental variation signal stimulus,
Physical property can occur to change accordingly, have certain environment-responsive, this intelligent behavior is applied in drug release body
System, can effective regulating medicine release time and position, realize Targeting delivery；But most of polymer machinery performance and stabilization
Property is poor, while lower specific surface keeps its drugloading rate relatively low, these disadvantages are subject to certain restrictions it in practical applications；
With the development of nanotechnology, people are grafted functional macromolecule polymer as control switch on the surface of mesoporous material,
Inorganic-organic mesoporous silicon oxide composite nano materials obtained, both drugloading rate with higher and good stability, together
When to external environment have preferable responsiveness, construct intelligentized drug delivery system；Neetu Singh etc.
(J.Am.Chem.Soc.2011,133,19582-19585) passes through free radical polymerization for polyethylene glycol N- isopropyl acrylamide
Amine (PEG-co-PNIPAM) is wrapped in the surface of meso-porous titanium dioxide nanoparticle, obtains the mesoporous dioxy with temperature sensitivity
SiClx composite nanoparticle, and applied in drug delivery system, with the blank mesoporous two for not wrapping up high molecular polymer
Silicon oxide nanoparticle is compared, and certain temperature sensitive responsiveness and sustained release performance are shown；(the European Journal such as Chen
Of Pharmaceutics and Biopharmaceutics, 2013,85 (3): 406-412) etc. will have pH/ temperature dual
Sensitive polymer poly n-isopropyl acrylamide-polyacrylic acid P (NIPAM-co-AA) is grafted in meso-porous titanium dioxide nanoparticle
Surface, applied in drug delivery system as pharmaceutical carrier, show preferable responsiveness；(the ACS such as Wu
Applied Materials&Interfaces, 2013,5 (21): 10895-10903) will be amino modified after meso-porous titanium dioxide
Silicon is carried out with poly-N-isopropyl acrylamide -18 rouge of polymethylacrylic acid-polyacrylic acid by hydrogen bond action compound, is obtained
Composite nanoparticle in drug delivery system have pH/ temperature doubling sensitivity.Mesoporous dioxy prepared by above method
SiClx composite nanoparticle shows certain environment-responsive in drug delivery system, but is wrapped in mesoporous silicon oxide
The high molecular polymer biocompatibility and biodegradability on surface are poor, are based on current present Research, potential in order to reduce
The toxicity of drug, in recent years, many nature polymer are also applied to medicine sustained and controlled release field, such as chitosan, polylactic acid etc.,
A kind of inexpensive, good biocompatibility and biodegradable high molecular polymer are found, ties it mutually with mesoporous silicon oxide
Close, obtain not only have pH/ temperature doubling sensitivity again biodegradable mesoporous silicon oxide composite nanoparticle with centainly
Realistic meaning and applicable value.
Summary of the invention
In view of the deficiencies of the prior art, the present invention provides a kind of pH/ temperature sensitivity double-response type nanometer medicines
Object carrier and its preparation and application, technical problem to be solved are to filter out a kind of biocompatibility and biodegradability
Good high molecular polymer and mesoporous silicon dioxide nano particle is compound, obtain pH/ temperature sensitivity double-response performance more preferably,
The slow controlled release carrier of more practical hydrophobic drug.
The present invention is to realize goal of the invention, is adopted the following technical scheme that
The present invention discloses a kind of pH/ temperature sensitivity double-response type nano-medicament carrier first, it is characterized in that: institute
Stating double-response type nano-medicament carrier is to pass through hydrogen bond action in the mesoporous silicon dioxide nano particle sublist face of amino functional
Wrap up the block copolymer with pH/ temperature sensitivity.
As a further improvement of the present invention, the block copolymer with pH/ temperature sensitivity is the poly- second of polylactic acid-
Glycol-poly-N-isopropyl acrylamide-acrylic acid PEG-PLA-b-P (NIPAM-co-AA), shown in structural formula such as formula (1):
Wherein, P represents poly-N-isopropyl acrylamide-acrylic acid Poly (NIPAM-co-AA), structural formula such as formula (2) institute
Show:
The invention also discloses the preparation methods of the pH/ temperature sensitivity double-response type nano-medicament carrier, including
Following steps:
Step 1, using mesoporous silicon dioxide nano particle of high-sequential as carrier, with amino-containing silane coupling agent be change
Property agent, its surface is modified, obtain amino functional mesoporous silicon dioxide nano particle；
Step 2, by mesoporous silicon dioxide nano particle of the amino functional with pH/ temperature sensitivity block
The solution of copolymer is mixed, and is stirred at room temperature for 24 hours, then through centrifugation, washing and drying, i.e. acquisition pH/ temperature sensitivity
Double-response type nano-medicament carrier.
As a further improvement of the present invention, the preparation process of mesoporous silicon dioxide nano particle of the high-sequential
Are as follows: by surfactant quaternary ammonium salt CnH2n+1(CH3)3NBr (n=12,14,16 and 18) is mixed with deionized water, is stirred molten
The molar ratio of solution, surfactant and water is 1:10000-20000；1-2mol/L NaOH solution is added, adjusts pH value to 8-
11；Then ethyl orthosilicate is added, the molar ratio of ethyl orthosilicate and surfactant is 1:0.15-0.4；It is warming up to 80
DEG C, 2-4h is reacted, white flock precipitate is generated；Through suction filtration, washing, drying, gained white powder calcines 4-6h at 500 DEG C,
Obtain ball-type mesoporous silicon dioxide nano particle of high-sequential.Gained ball-type mesoporous silicon dioxide nano particle has 2-
The meso-hole structure of the high-sequential of 4nm, spherical particles size is adjustable from 180nm-600nm.
As a further improvement of the present invention, method modified described in step 1 are as follows: by mesoporous silicon dioxide nano particle point
It is dispersed in dehydrated alcohol, acquisition mixed solution, the mass ratio of mesoporous silicon dioxide nano particle and dehydrated alcohol is 1:100-
200；By amino-containing silane coupling agent (gamma-aminopropyl-triethoxy-silane, N- β (aminoethyl) gamma-aminopropyl-triethoxy silicon
Alkane or 3- (2- aminoethylamino) propyl trimethoxy silicane) be added drop-wise in the mixed solution, silane coupling agent with it is mesoporous
The mass ratio of Nano particles of silicon dioxide is 1:20-50；Heating reflux reaction 4h；Products therefrom is dry through suction filtration, washing, vacuum
Dry mesoporous silicon dioxide nano particle to get amino functional.
As a further improvement of the present invention, in step 2, the mesopore silicon dioxide nano material of the amino functional with
The mass ratio of the block copolymer with pH/ temperature sensitivity is 100:5-20.
The invention also discloses the applications of the pH/ temperature sensitivity double-response type nano-medicament carrier, and being will be described
Carrier of the pH/ temperature sensitivity double-response type nanoparticle as hydrophobic drug, and applied in medicine sustained and controlled release body
In system, specific method is: it first by the solution of its stain to hydrophobic drug, is stirred at room temperature, is then centrifuged for, washs and dries,
It is loaded into hydrophobic drug in the mesopore orbit of nano-medicament carrier, obtains the laden composite material of drug.
As a further improvement of the present invention, the pH/ temperature sensitivity double-response type nano-medicament carrier with it is hydrophobic
Property drug mass ratio be 1:3-6.
Compared with the prior art, the beneficial effects of the present invention are embodied in:
1, the present invention selects PEG-PLA-b-P (NIPAM-co-AA) and amino modified mesoporous silicon dioxide nano particle
Compound, biocompatibility and biodegradability are good, and gained composite material has preferable dispersed, more uniform size and can
The particle size of tune, and preferable pH/ temperature sensitivity is shown in medicine sustained and controlled release system, therefore the nano-medicament carrier
Therapeutic field of tumor with good application prospect.
2, nano-medicament carrier preparation process of the invention is simple, at low cost.
Detailed description of the invention
Fig. 1 is the pH/ temperature sensitivity double-response type mesoporous silicon oxide composite nanoparticle prepared in embodiment 2
(P@MSN-180-5) stereoscan photograph；
Fig. 2 is pH/ temperature sensitivity dual responsiveness mesoporous silicon oxide composite nanoparticle (P@prepared by embodiment 4
MSN-500-5 nitrogen adsorption desorption curve (Fig. 2 (a)) and graph of pore diameter distribution (Fig. 2 (b)))；
Fig. 3 is that pH/ temperature sensitivity double-response type mesoporous silicon oxide composite nanoparticle (P@is synthesized in embodiment 6
MSN-180-15) drug release patterns in different environments.
Specific embodiment
Below in conjunction with embodiment, detailed, clear description is carried out to specific embodiments of the present invention, it is clear that institute
The embodiment of description is only a part of the embodiments of the present invention, instead of all the embodiments, based on the embodiment of the present invention, this
The those of ordinary skill in field does not make every other embodiment obtained under the premise of creative labor, belongs to this more
Invent the range of protection.
Embodiment 1
It weighs 1.0g cetyl trimethylammonium bromide to be added in 600mL water, after ultrasound to solution clarification, by 3.0mL
The NaOH solution of 2mol/L is added dropwise in the reaction system, and the ethyl orthosilicate of 5mL is added, and is warming up to 80 DEG C, mechanical stirring
After reacting 2h, the white precipitate of generation is filtered, is washed with deionized water to neutrality, drying for 24 hours, obtains white in 80 DEG C of drying boxes
Powder is sub (MSNs-80) for the ball-type mesoporous silicon dioxide nano particle of 80nm in 550 DEG C of roasting 5h, i.e. acquisition average grain diameter.
It weighs MSNs-80 1.0g to be added in 126mL dehydrated alcohol, 0.05mL 3- (2- aminoethylamino) then is added
Propyl trimethoxy silicane, 70 DEG C of reflux 4h, reaction terminate to wash sample with a large amount of dehydrated alcohol, finally filter 80
DEG C vacuum drying 12h, obtain the mesoporous silicon dioxide nano particle (MSN-80-NH of amino functional2)。
By 50mg copolymer polylactic acid-polyglycol-poly-N-isopropyl acrylamide-acrylic acid (PEG-PLA-b-P
(NIPAM-co-AA)) it is dissolved in 20mL water, 1.0g MSN-80-NH is then added2, at room temperature magnetic agitation for 24 hours, with distillation
Water is centrifuged sample surfaces, is washed, and is dried in vacuo for 24 hours at 50 DEG C, and pH/ temperature sensitivity dual responsiveness Jie is prepared
Hole silica composite nanoparticle (P@MSN-80-5).
Embodiment 2
It using the experimentation of embodiment 1, is different from place and is:, will when synthesizing mesoporous silicon dioxide nanoparticle
The NaOH solution of 4.0mL 2mol/L is added dropwise in reaction system, and the obtained sub- average grain diameter of mesoporous silicon dioxide nano particle is
PH/ temperature sensitivity dual responsiveness mesoporous silicon oxide composite nanoparticle (P@MSN-180-5) is prepared in 180nm.
Embodiment 3
It using the experimentation of embodiment 1, is different from place and is:, will when synthesizing mesoporous silicon dioxide nanoparticle
The NaOH solution of 4.5mL 2mol/L is added dropwise in reaction system, and the obtained sub- average grain diameter of mesoporous silicon dioxide nano particle is
PH/ temperature sensitivity dual responsiveness mesoporous silicon oxide composite nanoparticle (P@MSN-280-5) is prepared in 280nm.
Embodiment 4
It using the experimentation of embodiment 1, is different from place and is:, will when synthesizing mesoporous silicon dioxide nanoparticle
The NaOH solution of 5.0mL 2mol/L is added dropwise in reaction system, and the obtained sub- average grain diameter of mesoporous silicon dioxide nano particle is
PH/ temperature sensitivity dual responsiveness mesoporous silicon oxide composite nanoparticle (P@MSN-500-5) is prepared in 500nm.
Embodiment 5
Using the experimentation of embodiment 2, it is different from place and is: copolymer polylactic acid-polyglycol used-poly- N-
N-isopropylacrylamide-acrylic acid (PEG-PLA-b-P (NIPAM-co-AA)) quality is 100mg, and it is quick that pH/ temperature is prepared
Perceptual dual responsiveness mesoporous silicon oxide composite nanoparticle (P@MSN-180-10).
Embodiment 6
Using the experimentation of embodiment 2, it is different from place and is: copolymer polylactic acid-polyglycol used-poly- N-
N-isopropylacrylamide-acrylic acid (PEG-PLA-b-P (NIPAM-co-AA)) quality is 150mg, and it is quick that pH/ temperature is prepared
Perceptual dual responsiveness mesoporous silicon oxide composite nanoparticle (P@MSN-180-15).
Embodiment 7
Using the experimentation of embodiment 2, it is different from place and is: copolymer polylactic acid-polyglycol used-poly- N-
N-isopropylacrylamide-acrylic acid (PEG-PLA-b-P (NIPAM-co-AA)) quality is 200mg, and it is quick that pH/ temperature is prepared
Perceptual dual responsiveness mesoporous silicon oxide composite nanoparticle (P@MSN-180-20).
Embodiment 8
Using the experimentation of embodiment 1, it is different from place and is: selecting 0.05mL N- β (aminoethyl) γ-ammonia third
It is compound that pH/ temperature sensitivity dual responsiveness mesoporous silicon oxide is prepared as silane coupling agent in ethyl triethoxy silicane alkane
Nanoparticle.
Embodiment 9
It weighs 1.0g dodecyl trimethyl ammonium bromide to be added in 600mL water, after ultrasound to solution clarification, by 3.0mL
The NaOH solution of 2mol/L is added dropwise in the reaction system, and the ethyl orthosilicate of 5mL is added, and is warming up to 80 DEG C, mechanical stirring
After reacting 2h, the white precipitate of generation is filtered, is washed with deionized water to neutrality, drying for 24 hours, obtains white in 80 DEG C of drying boxes
For powder in 550 DEG C of roasting 5h, i.e. acquisition ball-type mesoporous silicon dioxide nano particle is sub (MSNs-1).
MSNs-1 1.0g after weighing roasting is added in 126mL dehydrated alcohol, and 0.05mL 3- (2- amino second is then added
Base amino) propyl trimethoxy silicane, 70 DEG C of reflux 4h, reacting terminates to wash sample with a large amount of dehydrated alcohol, most
Afterwards filter 80 DEG C of vacuum drying 12h, obtain it is amino modified after sample i.e. MSNs-1-NH2。
By 50mg copolymer polylactic acid-polyglycol-poly-N-isopropyl acrylamide-acrylic acid (PEG-PLA-b-P
(NIPAM-co-AA)) it is dissolved in 20mL water, 1.0g MSN-80-NH is then added2, at room temperature magnetic agitation for 24 hours, with distillation
Water is centrifuged sample surfaces, is washed, and is dried in vacuo for 24 hours at 50 DEG C, and pH/ temperature sensitivity dual responsiveness Jie is prepared
Hole silica composite nanoparticle (P@MSN-1-5).
Analysis of experiments is carried out to the product that the various embodiments described above are prepared:
Electronic Speculum characterization is scanned to the product of each embodiment, Fig. 1 is that pH/ temperature sensitivity prepared by embodiment 2 is double
The stereoscan photograph of the responsibility mesoporous silica composite nanoparticle (P@MSN-180-5) of weight, as can be seen from the figure produces
Object has preferable dispersibility, more uniform size, remaining embodiment sample experiments result obtained has same characteristics.
The product of each embodiment is carried out to carry out isothermal nitrogen adsorption desorption test, Fig. 2 is pH/ temperature prepared by embodiment 4
Spend the nitrogen adsorption desorption curve (Fig. 2 of sensibility dual responsiveness mesoporous silicon oxide composite nanoparticle (P@MSN-500-5)
(a)) and graph of pore diameter distribution (Fig. 2 (b)), as can be seen from the figure composite nanoparticle pore diameter range is between 2-4nm, specific surface
For 540m2/g。
By pH/ temperature sensitivity dual responsiveness mesoporous silicon oxide composite nanoparticle (P@prepared by embodiment 6
MSN-180-15 drug loading) is carried out, and investigates its medicine-releasing performance under various circumstances, drug release kinetics curve
As shown in Figure 3.Specific step is as follows for drug loading: above-mentioned composite nanoparticle being dispersed in the solution containing drug, room temperature
For 24 hours, then the system is filtered, is washed for lower stirring, is dried in vacuo 12h, final to obtain the laden composite nanoparticle of drug.
Drug release carries out in 20mL phosphate buffer solution PBS (pH=7.4 and pH=2.0) respectively, and temperature is controlled respectively 25
DEG C and 40 DEG C.The sample tabletting of drug will be loaded, be fitted into bag filter, be placed in certain volume release liquid, maintains water bath with thermostatic control
Concussion.Separated in time pipettes 1mL release liquid and with its absorbance of ultraviolet determination, calculates its accumulative release rate.It is discharged from Fig. 3
As can be seen that the composite nanoparticle shows pH/ temperature dual responsiveness, release temperature in drug delivery system in curve
Under conditions of 40 DEG C, it is slow in pH=2.0 that burst size of the drug in pH=7.4 buffer solution in composite nanoparticle is greater than it
Rush burst size in solution；And in the buffer solution of pH=7.4, temperature is apparently higher than it in 40 DEG C of condition drug release rate
Rate of release under the conditions of 25 DEG C.The composite nano-granule of obtained different-grain diameter and different package amounts in other embodiments
Son equally shows preferable pH/ temperature double-response performance in drug release process.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (10)
1. a kind of pH/ temperature sensitivity double-response type nano-medicament carrier, it is characterised in that: the double-response type nanometer medicine
Object carrier is that have pH/ temperature sensitive by hydrogen bond action package in the mesoporous silicon dioxide nano particle sublist face of amino functional
The block copolymer of property.
2. pH/ temperature sensitivity double-response type nano-medicament carrier according to claim 1, it is characterised in that: described
Block copolymer with pH/ temperature sensitivity is polylactic acid-polyglycol-poly-N-isopropyl acrylamide-acrylic acid PEG-
PLA-b-P (NIPAM-co-AA), shown in structural formula such as formula (1):
Wherein, P represents poly-N-isopropyl acrylamide-acrylic acid Poly (NIPAM-co-AA), shown in structural formula such as formula (2):
3. a kind of preparation method of pH/ temperature sensitivity double-response type nano-medicament carrier as claimed in claim 1 or 2, special
Sign is, includes the following steps:
Step 1, using mesoporous silicon dioxide nano particle of high-sequential as carrier, with amino-containing silane coupling agent be modified
Agent is modified its surface, obtains mesoporous silicon dioxide nano particle of amino functional；
Step 2, by mesoporous silicon dioxide nano particle of the amino functional with pH/ temperature sensitivity block copolymerization
The solution of object is mixed, and is stirred at room temperature for 24 hours, and then through centrifugation, washing and drying, i.e. acquisition pH/ temperature sensitivity is dual
Response type nano pharmaceutical carrier.
4. preparation method according to claim 3, it is characterised in that: the mesoporous silicon dioxide nano particle of the high-sequential
The preparation process of son are as follows: by surfactant quaternary ammonium salt CnH2n+1(CH3)3NBr (n=12,14,16 and 18) and deionized water into
The molar ratio of row mixing, stirring and dissolving, surfactant and water is 1:10000-20000；1-2mol/L NaOH solution is added,
PH value is adjusted to 8-11；Then ethyl orthosilicate is added, the molar ratio of ethyl orthosilicate and surfactant is 1:0.15-
0.4；80 DEG C are warming up to, 2-4h is reacted, generates white flock precipitate；Through suction filtration, washing, drying, gained white powder is at 500 DEG C
Lower calcining 4-6h, i.e. ball-type mesoporous silicon dioxide nano particle of acquisition high-sequential.
5. the preparation method according to claim 4, it is characterised in that: gained ball-type mesoporous silicon dioxide nano particle has
The meso-hole structure of the high-sequential of 2-4nm, spherical particles size is adjustable from 180nm-600nm.
6. preparation method according to claim 3, it is characterised in that: modified method described in step 1 are as follows: by mesoporous dioxy
SiClx nanoparticle is dispersed in dehydrated alcohol, obtains mixed solution, the matter of mesoporous silicon dioxide nano particle and dehydrated alcohol
Amount is than being 1:100-200；
Amino-containing silane coupling agent is added drop-wise in the mixed solution, silane coupling agent and mesoporous silicon dioxide nano particle
Mass ratio be 1:20-50；Heating reflux reaction 4h；Products therefrom is through suction filtration, washing, vacuum drying to get amino functional
Mesoporous silicon dioxide nano particle.
7. preparation method according to claim 3, it is characterised in that: in step 2, the mesoporous dioxy of the amino functional
The mass ratio of SiClx nano material and the block copolymer with pH/ temperature sensitivity is 100:5-20.
8. a kind of application of pH/ temperature sensitivity double-response type nano-medicament carrier as claimed in claim 1 or 2, feature exist
In: it is and to be applied using the pH/ temperature sensitivity double-response type nano-medicament carrier as the carrier of hydrophobic drug
In medicine sustained and controlled release system.
9. application according to claim 8, which is characterized in that specific method is: first that the pH/ temperature sensitivity is double
Weight response type nano pharmaceutical carrier is impregnated into the solution of hydrophobic drug, is stirred at room temperature, is then centrifuged for, washs and dries, make
Hydrophobic drug is loaded into the mesopore orbit of nano-medicament carrier, obtains the laden composite material of drug.
10. application according to claim 8, it is characterised in that: the pH/ temperature sensitivity double-response type Nano medication
The mass ratio of carrier and hydrophobic drug is 1:3-6.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910635085.3A CN110200944A (en) | 2019-07-15 | 2019-07-15 | A kind of pH/ temperature sensitivity double-response type nano-medicament carrier and its preparation and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910635085.3A CN110200944A (en) | 2019-07-15 | 2019-07-15 | A kind of pH/ temperature sensitivity double-response type nano-medicament carrier and its preparation and application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110200944A true CN110200944A (en) | 2019-09-06 |
Family
ID=67797420
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910635085.3A Pending CN110200944A (en) | 2019-07-15 | 2019-07-15 | A kind of pH/ temperature sensitivity double-response type nano-medicament carrier and its preparation and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110200944A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111249467A (en) * | 2020-01-09 | 2020-06-09 | 华东理工大学 | Tumor self-targeting multi-stage response type mesoporous silicon drug delivery system and preparation method thereof |
| CN112494421A (en) * | 2020-12-23 | 2021-03-16 | 华中科技大学 | Slow-release soluble microneedle, preparation method and application |
| CN112680038A (en) * | 2020-12-15 | 2021-04-20 | 南开大学 | Water-based super-hydrophobic nano composite coating with controllable water drop adhesion function and preparation method thereof |
| CN113142199A (en) * | 2021-04-25 | 2021-07-23 | 扬州大学 | Preparation method and application of buprofezin-loaded mesoporous silica nanoparticle controlled release agent |
| CN114106416A (en) * | 2021-12-28 | 2022-03-01 | 滨州学院 | Preparation method and application of dual-response halloysite nano container |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109172542A (en) * | 2018-10-25 | 2019-01-11 | 华南理工大学 | A kind of multistage pH response mesoporous silicon oxide composite nanoparticle and its application |
-
2019
- 2019-07-15 CN CN201910635085.3A patent/CN110200944A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109172542A (en) * | 2018-10-25 | 2019-01-11 | 华南理工大学 | A kind of multistage pH response mesoporous silicon oxide composite nanoparticle and its application |
Non-Patent Citations (5)
| Title |
|---|
| CHANG, BAISONG ET AL.: ""Thermo and pH dual responsive, polymer shell coated, magnetic mesoporous"", 《JOURNAL OF MATERIALS CHEMISTRY》 * |
| SINGH, NEETU ET AL.: ""Bioresponsive Mesoporous Silica Nanoparticles for Triggered Drug Release"", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
| 孙少平等主编: "《高分子材料在纳米给药系统中的应用》", 31 August 2017, 出版发行:黑龙江大学出版社 * |
| 金效齐: ""基于双模型介孔SiO2构筑具有双重环境响应型药物控释性能"", 《中国博士学位论文全文数据库 工程科技Ⅰ辑》 * |
| 金效齐等: ""基于介孔二氧化硅pH/温度响应型复合纳米粒子的制备"", 《第18届全国分子筛学术大会论文集（下）》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111249467A (en) * | 2020-01-09 | 2020-06-09 | 华东理工大学 | Tumor self-targeting multi-stage response type mesoporous silicon drug delivery system and preparation method thereof |
| CN112680038A (en) * | 2020-12-15 | 2021-04-20 | 南开大学 | Water-based super-hydrophobic nano composite coating with controllable water drop adhesion function and preparation method thereof |
| CN112494421A (en) * | 2020-12-23 | 2021-03-16 | 华中科技大学 | Slow-release soluble microneedle, preparation method and application |
| CN112494421B (en) * | 2020-12-23 | 2022-09-20 | 华中科技大学 | Slow-release soluble microneedle, preparation method and application |
| CN113142199A (en) * | 2021-04-25 | 2021-07-23 | 扬州大学 | Preparation method and application of buprofezin-loaded mesoporous silica nanoparticle controlled release agent |
| CN114106416A (en) * | 2021-12-28 | 2022-03-01 | 滨州学院 | Preparation method and application of dual-response halloysite nano container |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110200944A (en) | A kind of pH/ temperature sensitivity double-response type nano-medicament carrier and its preparation and application | |
| CN108046276B (en) | A kind of polyethyleneglycol modified preparation of mesoporous silica nano-particle of carboxy blocking and application thereof | |
| Bai et al. | Synthesis and characterization of paclitaxel-imprinted microparticles for controlled release of an anticancer drug | |
| Jia et al. | pH-responsive polysaccharide microcapsules through covalent bonding assembly | |
| Pan et al. | Thermo-responsive molecularly imprinted nanogels for specific recognition and controlled release of proteins | |
| CN105853365B (en) | A kind of silica-chitosan for having both pH responsiveness and folate-targeted and loading ursolic acid-folic acid nano material and application | |
| Ma et al. | Synthesis and biological response of casein-based silica nano-composite film for drug delivery system | |
| Wang et al. | Facile preparation of magnetic 2-hydroxypropyltrimethyl ammonium chloride chitosan/Fe3O4/halloysite nanotubes microspheres for the controlled release of ofloxacin | |
| CN107854449A (en) | A kind of composite nano-microsphere with medicine controlled releasing performance and its preparation method and application | |
| Guo et al. | Glucose-sensitive polyelectrolyte nanocapsules based on layer-by-layer technique for protein drug delivery | |
| Yang et al. | A facile preparation of targetable pH-sensitive polymeric nanocarriers with encapsulated magnetic nanoparticles for controlled drug release | |
| CN108653238A (en) | A kind of lignin-histidine medicine-carried nano particles and preparation method thereof with pH responses | |
| CN107632002B (en) | Composite fluorescent biosensor and preparation method and application thereof | |
| Li et al. | Intracellular pH-responsive mesoporous hydroxyapatite nanoparticles for targeted release of anticancer drug | |
| CN109172542B (en) | Multi-stage pH response mesoporous silica composite nanoparticle and application thereof | |
| Bach et al. | Poly (glycidyl methacrylate) grafted CdSe quantum dots by surface-initiated atom transfer radical polymerization: Novel synthesis, characterization, properties, and cytotoxicity studies | |
| CN108670960A (en) | A kind of hyaluronic acid oligosaccharide-chitosan microball and the preparation method and application thereof containing Docetaxel | |
| CN111249253B (en) | Preparation method of core-shell structure stimulus response type drug carrier and drug release method | |
| CN107353372A (en) | A kind of preparation method of the uncoupler imprint surface polymer of nNOS PSD 95 based on magnetic mesoporous molecular sieve | |
| CN108641092B (en) | Preparation method of supramolecular polymer composite micelle based on hydrogen bond | |
| CN102936321B (en) | Living polymerization preparation method for polyacrylic acid ball brush and application of polyacrylic acid ball brush | |
| Qin et al. | Polymer-modified halloysite nanotubes with high adhesion and UV-shielding properties for chlopyrifos application on cotton leaves | |
| CN106389342A (en) | Preparation method of hydroxyapatite/tannic acid composite particle capable of adjusting and controlling release speed of methylene blue monomer | |
| CN105497903B (en) | A kind of drug delivery carrier of double control and preparation method thereof based on inorganic nano silicon materials | |
| CN105181662B (en) | A kind of method that qualitative detection is supported on function nano distribution of particles in polysaccharide microsphere |
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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20190906 |
|
| RJ01 | Rejection of invention patent application after publication |