CN101411877A - Method for preparing thermosensitive nano medicament carrier with dual-target magnetism and folacin - Google Patents
Method for preparing thermosensitive nano medicament carrier with dual-target magnetism and folacin Download PDFInfo
- Publication number
- CN101411877A CN101411877A CNA2008102027840A CN200810202784A CN101411877A CN 101411877 A CN101411877 A CN 101411877A CN A2008102027840 A CNA2008102027840 A CN A2008102027840A CN 200810202784 A CN200810202784 A CN 200810202784A CN 101411877 A CN101411877 A CN 101411877A
- Authority
- CN
- China
- Prior art keywords
- nano
- medicament carrier
- folic acid
- magnetic
- preparation
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method for a temperature-sensitive nano medicament carrier with magnetism and folic acid double targets. The preparation method comprises the following steps: carrying out oleophylic modification for surfaces of ferroferric oxide nano particles; coating poly N-isopropyl acrylamide on the surfaces of ferroferric oxide nano particles to prepare compound seed microspheres with hollow cavity structures; coating copolymer of the N-isopropyl acrylamide and methacrylic acid dehydrated glyceride on the surfaces of the compound seed microspheres to prepare nano compound microspheres; making the surfaces of the nano compound microspheres carry with amino; and combining the nano compound microspheres with amino with folic acid to obtain the temperature-sensitive nano medicament carrier. The phase variation temperature of the nano medicament carrier is between 32 and 42 DEG C, and the nano medicament carrier is used for carrying anticancer medicament amycin. The preparation method has the advantages that the preparation technique is clear and comprehensive; the obtained nano medicament carrier has multiple functions of magnetic target, folic acid target, temperature sensitivity, hollow cavity structure, and the like; and the nano medicament carrier shows good application effect in cell experiments, and is a comparatively ideal medicament carrier.
Description
Technical field
The present invention relates to a kind of preparation method of novel thermosensitive nano medicament carrier, especially a kind of preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target, and pass through thermosensitive nano medicament carrier of this preparation method acquisition and uses thereof.
Background technology
According to a large amount of studies show that, folacin receptor be a kind of in multiple cancerous cell extensive excessive existence and can and folate molecule special interactional material takes place.Utilize the distinctive interaction of folic acid and folacin receptor, people modify folic acid the anti-cancer medicament carrier of various nano-scales usually as special targeted molecular, play targeting recognition reaction, thereby improve the transmission efficiency of medicine, can reduce side effects of pharmaceutical drugs simultaneously cancerous cell.
In various carriers, the carrier with cavity structure is because of its distinctive character, and the adjustable permeability of for example bigger interior space dimension and shell loading DNA, has obtained extensive studies and application in the field of protein and various drug molecules.In actual applications, the regulating and controlling carrier is the focus that people study for the penetrating power of foreign molecules always, because carrier is related to the loading and the release of foreign molecules to the penetrating power of foreign molecules, is very important.In order further to improve the permeability of carrier, a kind of more feasible method is exactly a kind of stimulation that can be to external world of design preparation, temperature for example, and the carrier of specific response is made in pH value and magnetic field.Thereby control the penetrating power of carrier for foreign molecules by the adjusting of environmental stimuli.
Based on the magnetic of ferriferrous oxide nano-particle, its functional microsphere material is in cell separation, immobilized enzyme, and the magnetic target drug-carrying, biological fields such as nuclear magnetic resonance all have a wide range of applications.And ferriferrous oxide nano-particle is proved to be just good biocompatibility.Poly-N-isopropyl acrylamide (PNIPAM) is a kind of polymer with temperature-responsive, and it has a lowest critical solution temperature (LCST) about 32 ℃.When temperature less than 32 ℃ the time, PNIPAM shows hydrophilic; When temperature greater than 32 ℃ the time, it shows hydrophobicity.And the LCST of PNIPAM is adjustable in a big way, adds the hydrophilic polymerized monomer LCST that can raise, and can reduce LCST otherwise add the hydrophobicity comonomer.This special temperature-sensitive of PNIPAM makes it all obtain the extensive studies report in the controllable release field of drug delivery and medicine.
Based on above information, a kind of magnetic targeting and folic acid targeting of having concurrently of design preparation, the nano-medicament carrier with cavity structure that has temperature-sensing property simultaneously will be the once fine exploration to the drug delivery field.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target.
Another technical problem to be solved by this invention is to provide a kind of thermosensitive nano medicament carrier with magnetic and folic acid dual-target of above-mentioned preparation method acquisition.
A technical problem more to be solved by this invention is to provide a kind of purposes of above-mentioned thermosensitive nano medicament carrier.
The present invention solves the problems of the technologies described above the technical scheme of being taked: a kind of preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target comprises the steps:
The first step: with the oleophylic modification of ferriferrous oxide nano-particle surface;
Second step: coat poly-N-isopropyl acrylamide (PNIPAM) on the ferriferrous oxide nano-particle surface by the mini-emulsion polymerization method, make the compound seed microsphere of tool cavity structure;
The 3rd step:, make composite nano-microsphere at the copolymer of compound seed microsphere surface by precipitation polymerization process coating N-N-isopropylacrylamide (NIPAM) and methacrylic dehydrated glyceride (GMA);
The 4th step: the composite nano-microsphere surface is with amino;
The 5th step: will combine with folic acid with amino composite nano-microsphere, obtain thermosensitive nano medicament carrier.
The present invention at first uses ferriferrous oxide nano-particle through modifications such as oleic acid as magnetic material, and obtain inside by improved mini-emulsion polymerization method and have cavity structure, be nuclear with the ferriferrous oxide nano-particle, with PNIPAM the compound seed microsphere of shell; Coat the copolymer of NIPAM and GMA again outside the seed microsphere by precipitation polymerization process, further the copolymer with NIPAM and GMA is a shell, obtains the complex microsphere that the surface has epoxide group; Then, the epoxide group of microsphere surface can be used excess of ammonia base reagent open at normal temperatures, obtains the surface and has amino composite nano-microsphere; At last, with the amino reaction on folic acid and complex microsphere surface, carboxyl on the folate molecule and amino reaction generate amido link, thereby folate molecule is received microsphere surface, finally obtain having the thermosensitive nano medicament carrier of magnetic and folic acid dual-target.
Described ferriferrous oxide nano-particle is the ferriferrous oxide nano-particle of superparamagnetism, makes by chemical coprecipitation.
On the basis of such scheme, in the first step, adopt the ferriferrous oxide nano-particle of superparamagnetism, oleophylic is modified as the ferriferrous oxide nano-particle surface is obtained magnetic fluid by oleophylic agent modification, and described oleophylic agent is oleic acid, oleyl amine or three n-octyl oxygen phosphorus (TOPO) etc.
On the basis of such scheme, in second step, ferriferrous oxide nano-particle and the monomeric mass ratio of N-N-isopropylacrylamide (NIPAM) are 1:5～15 in the described compound seed microsphere, and the particle diameter of the compound seed microsphere of acquisition is at 80～120nm.
Wherein, ferriferrous oxide nano-particle and the monomeric mass ratio of N-N-isopropylacrylamide can be specially 1:5, and 6,8,10,12,13 or 15; Particle size distribution can be 80,90,100,110,120nm.
The mini-emulsion polymerization preparation method of compound seed microsphere is specifically as follows:
After the magnetic fluid washing that obtains in the modification of first step ferriferrous oxide nano-particle, add solvent acetic acid butyl ester and azodiisobutyronitrile (AIBN), after being uniformly dispersed, and dodecylbenzene sodium sulfonate (SDBS) solution mixes ultrasonic formation stable emulsion;
With N-N-isopropylacrylamide monomer (NIPAM) and N, N '-methylene-bisacrylamide (MBA) dissolving mixes with described stabilizing solution, carries out the monomeric polymerization of ferriferrous oxide nano-particle and NIPAM again;
The course of reaction condition is: earlier logical nitrogen 20～50 minutes, reacted 3～6 hours down for 70～80 ℃ in reaction temperature again.
Concrete, the time of logical nitrogen can be 20,30,40 or 50 minutes; Reaction temperature can be 70,72,75,78 or 80 ℃, and the response time can be 3,4,5 or 6 hours.
On the basis of such scheme, in the 3rd step, the particle diameter of described composite nano-microsphere is at 180～220nm.Concrete particle size distribution can be 180,190,200,210,220nm.
The copolymer that coats N-N-isopropylacrylamide (NIPAM) and methacrylic dehydrated glyceride (GMA) by precipitation polymerization process outside the seed microsphere obtains being specifically as follows of composite nano-microsphere:
Add N-N-isopropylacrylamide monomer (NIPAM) in the compound seed microsphere dispersion liquid that in second step, obtains, methacrylic dehydrated glyceride (GMA), N, N '-methylene-bisacrylamide (MBA) cross-linking agent, earlier logical nitrogen 20～50 minutes, add the potassium peroxydisulfate initiator, reacted 3～6 hours down for 70～80 ℃ in reaction temperature again.
The time of logical nitrogen is specifically as follows 20,30,40 or 50 minutes; Reaction temperature can be 70,72,75,78 or 80 ℃, and the response time can be 3,4,5 or 6 hours.
On the basis of such scheme, in the 4th step, make the composite nano-microsphere surface with going up amino method be: composite nano-microsphere and amino reagent reacting, described amino reagent is hexamethylene diamine, ethylenediamine, butanediamine or mercaptoethylmaine etc.The following stirring of room temperature spent the night after adding amino reagent, and product separates with magnetic, and it is stand-by to wash repeatedly the back with water.
On the basis of such scheme, in the 5th step, earlier folic acid, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC.HCl), N-hydroxy-succinamide (NHS) are mixed in solvent, carry out priming reaction as mixing in the dimethyl sulfoxide (DMSO), again with the reaction of being with on the amino composite nano-microsphere.
With folic acid and EDC.HCl and NHS mixing stir-activating 0.5～2 hour, generally speaking, folic acid was 1:1.5～2.5:1.5～2.5 with the mol ratio of mixing of EDC.HCl, NHS, and is specifically as follows 1:1.5,1.8,2,2.2 or 2.5:1.5,1.8,2,2.2 or 2.5, preferred 1:2:2.In advance to folic acid activate more help after carboxyl and the reaction of the amino on composite nano-microsphere generation amido link on the folate molecule, thereby folate molecule is received microsphere surface.
Thermosensitive nano medicament carrier at above-mentioned preparation method acquisition with magnetic and folic acid dual-target, described thermosensitive nano medicament carrier has cavity structure, with the ferroso-ferric oxide is nuclear, copolymer with poly-N-isopropyl acrylamide, poly-N-isopropyl acrylamide and methacrylic dehydrated glyceride is a shell, finishing has the folic acid targeted molecular, and particle diameter is at 180～220nm.Concrete particle size distribution can be 180,190,200,210,220nm.This nano-medicament carrier has magnetic response speed faster, and volume can take place at a certain temperature to be changed mutually, and can stable dispersion in water.
On the basis of such scheme, the magnetic saturation intensity scope of thermosensitive nano medicament carrier is 5emu/g～40emu/g; Phase transition temperature is 32～42 ℃.
Concrete, the magnetic saturation intensity scope of thermosensitive nano medicament carrier can be 5,10,15,20,25,30,35 or 40emu/g; Phase transition temperature can be 32,35,38,40 or 42 ℃.
At the purposes of above-mentioned thermosensitive nano medicament carrier, be used to load anticancer drugs, doxorubicin.Thermosensitive nano medicament carrier can pass through hydrogen bond action or physisorption in aqueous solution, load amycin medicine molecule, and its envelop rate and carrying drug ratio can be controlled with pH value easily.The dispose procedure of amycin can be controlled by temperature and the pH value of regulating environment, shows rate of release faster under high temperature and low ph condition.Above-mentioned nano-medicament carrier by will being loaded with medicine and the cancerous cell that has a folacin receptor are cultivated together and are carried out cell experiment, and nano-medicament carrier has embodied good targeting characteristic.
On the basis of such scheme, the percentage by weight of the carrying drug ratio of described anticancer drugs, doxorubicin is 3～60%.Concrete, carrying drug ratio can for: 3,5,10,15,20,25,30,35,40,45,50,55 or 60%.
Excellent effect of the present invention is:
Preparation technology of the present invention is clear comprehensively, and the nano-medicament carrier that obtains has the magnetic targeting, folic acid targeting, multiple functions such as temperature sensitivity and cavity structure.The magnetic targeting of carrier makes carrier to assemble at specific position under the control in magnetic field; The folic acid targeting makes carrier have special target recognition function to cancerous cell; The temperature sensitivity of carrier can be used for realizing the controllable release of the medicine that loaded, can be controlled for the release of drug molecule by thermal stimulus; Thereby the cavity structure of carrier then makes carrier can load more drug molecule to be improved the efficient of drug delivery and reduces side effect; The present invention has shown good effect in cell experiment, be a kind of comparatively ideal pharmaceutical carrier.
Above mentality of designing has covered some basic problems that the drug delivery field is concerned about substantially, so product has comprehensive preferably.
Specific implementation method
Once the present invention is further illustrated by embodiment, but these embodiments do not limit the protection domain of this paper.
A kind of preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target,
Comprise the steps:
The first step: with the oleophylic modification of ferriferrous oxide nano-particle surface:
A certain amount of iron chloride and ferrous chloride (mol ratio 2:1) are dissolved in the water, logical nitrogen half an hour are warmed up to 60 ℃, add proper amount of sodium hydroxide solution, make ferriferrous oxide nano-particle;
In reaction system, drip an amount of oleic acid then slowly, after resulting reaction system was stablized 10 minutes, be heated to 90 ℃ and react half an hour, after reaction naturally cools to room temperature, with the hydrochloric acid solution conditioned reaction system pH to 4 of 1mol/L.Separate with attraction then, product washes with water 5 times, then respectively washs three times with dehydrated alcohol and acetone respectively again, and the product that finally obtains cyclohexane extraction distributed and saved obtains stable magnetic fluid.
Second step: coat poly-N-isopropyl acrylamide on the ferriferrous oxide nano-particle surface, make the compound seed microsphere of tool cavity structure:
Ferriferrous oxide nano-particle and NIPAM monomeric charge mass ratio are 1:10.
0.625g magnetic fluid (solid content 5.6%) behind acetone and absolute ethanol washing, is added 0.5g solvent acetic acid butyl ester and 10mg AIBN, after being uniformly dispersed and SDBS solution (75mg/30ml) mix ultrasonic formation stable emulsion;
Get 0.35g NIPAM, 0.047g MBA is dissolved in the 30ml water and the above-mentioned emulsion mix homogeneously, puts into the 100ml four-necked bottle, behind the logical nitrogen 30min, 76 ℃ down reaction stopped distributed and saved once more after product compound seed microsphere washes with water in 4 hours.
The 3rd step: at Fe
3O
4@PNIPAM compound seed microsphere surface coats the copolymer of N-N-isopropylacrylamide and methacrylic dehydrated glyceride, makes composite nano-microsphere:
To add 0.064g NIPAM in the 25g compound seed microsphere dispersion liquid, 0.02 GMA, 0.01g MBA behind the logical nitrogen 30min, adds 4mg potassium peroxydisulfate initiator, reacts 4 hours down at 76 ℃, and product separates with magnetic, and it is stand-by to wash the back with water.
The 4th step: it is amino that the composite nano-microsphere surface is with:
The Fe for preparing
3O
4In the @PNIPAM-co-PGMA composite nano-microsphere dispersion liquid, add to stir under the excessive hexamethylene diamine room temperature and spend the night, product separates with magnetic, and it is stand-by to wash repeatedly the back with water;
The 5th step: will combine with folic acid with amino composite nano-microsphere, obtain thermosensitive nano medicament carrier:
Mol ratio is the folic acid of 1:2:2, NHS, EDC is dissolved in a certain amount of dimethyl sulfoxide (DMSO), stir-activating 1 hour joins above-mentioned solution in the preprepared microsphere dispersion liquid then, adds the triethylamine catalyst, the lucifuge reaction is spent the night, product separates with magnetic, and after washing with water, and unreacted molecule is removed in dialysis.
Application examples
Get the thermosensitive nano medicament carrier 5mg that makes among the embodiment, the amycin that adds 5mg, be made into the solution of 10ml, after solution is adjusted to certain pH 5～10, room temperature stirs down and spends the night product centrifugalize, lyophilization, make the thermosensitive nano medicament carrier that is mounted with anticancer amycin, the percentage by weight of the carrying drug ratio of anticancer drugs, doxorubicin is 5～50%.
Claims (10)
1, a kind of preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target is characterized in that comprising the steps:
The first step: with the oleophylic modification of ferriferrous oxide nano-particle surface;
Second step: coat poly-N-isopropyl acrylamide on the ferriferrous oxide nano-particle surface, make the compound seed microsphere of tool cavity structure;
The 3rd step: the copolymer at compound seed microsphere surface coating N-N-isopropylacrylamide and methacrylic dehydrated glyceride makes composite nano-microsphere;
The 4th step: it is amino that the composite nano-microsphere surface is with;
The 5th step: will combine with folic acid with amino composite nano-microsphere, obtain thermosensitive nano medicament carrier.
2, the preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target according to claim 1, it is characterized in that: in the first step, adopt the ferriferrous oxide nano-particle of superparamagnetism, oleophylic is modified as ferriferrous oxide nano-particle surface by oleophylic agent modification, and described oleophylic agent is a kind of in oleic acid, oleyl amine, the three n-octyl oxygen phosphorus.
3, the preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target according to claim 1, it is characterized in that: in second step, ferriferrous oxide nano-particle and the monomeric mass ratio of N-N-isopropylacrylamide are 1:5～15 in the described compound seed microsphere, and particle diameter is at 80～120nm.
4, according to claim 1 or 3 described preparation methoies with thermosensitive nano medicament carrier of magnetic and folic acid dual-target, it is characterized in that: in second step, the preparation method of compound seed microsphere is:
After the washing of the magnetic fluid that obtains in the modification of first step ferriferrous oxide nano-particle, add solvent and azodiisobutyronitrile, after being uniformly dispersed and dodecylbenzene sodium sulfonate solution mix ultrasonic formation stable emulsion;
With N-N-isopropylacrylamide monomer and N, N '-methylene-bisacrylamide dissolving mixes with described stabilizing solution, carries out ferriferrous oxide nano-particle and the monomeric polymerization of N-N-isopropylacrylamide again;
The course of reaction condition is: earlier logical nitrogen 20～50 minutes, reacted 3～6 hours down for 70～80 ℃ in reaction temperature again.
5, the preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target according to claim 1 is characterized in that: in the 3rd step, the particle diameter of described composite nano-microsphere is at 180～220nm.
6, the preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target according to claim 1, it is characterized in that: in the 4th step, make the composite nano-microsphere surface with going up amino method be: composite nano-microsphere and amino reagent reacting, described amino reagent are a kind of in hexamethylene diamine, ethylenediamine, butanediamine, the mercaptoethylmaine.
7, the preparation method with thermosensitive nano medicament carrier of magnetic and folic acid dual-target according to claim 1, it is characterized in that: in the 5th step, earlier folic acid, 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, N-hydroxy-succinamide are mixed in solvent and carry out priming reaction, amino with band again composite nano-microsphere reaction.
8, the thermosensitive nano medicament carrier that obtains at the described preparation method of one of claim 1～7 with magnetic and folic acid dual-target, with the ferroso-ferric oxide is nuclear, copolymer with N-N-isopropylacrylamide and methacrylic dehydrated glyceride is the cavity structure of shell, finishing has the folic acid targeted molecular, and particle diameter is at 180～220nm.
9, the thermosensitive nano medicament carrier with magnetic and folic acid dual-target according to claim 8, it is characterized in that: the magnetic saturation intensity scope of thermosensitive nano medicament carrier is 5emu/g～40emu/g; Phase transition temperature is 32～42 ℃.
10, at the purposes of claim 8 or 9 described thermosensitive nano medicament carriers, be used to load anticancer drugs, doxorubicin, the percentage by weight of the carrying drug ratio of anticancer drugs, doxorubicin is 3～60%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008102027840A CN101411877A (en) | 2008-11-14 | 2008-11-14 | Method for preparing thermosensitive nano medicament carrier with dual-target magnetism and folacin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2008102027840A CN101411877A (en) | 2008-11-14 | 2008-11-14 | Method for preparing thermosensitive nano medicament carrier with dual-target magnetism and folacin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101411877A true CN101411877A (en) | 2009-04-22 |
Family
ID=40592755
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA2008102027840A Pending CN101411877A (en) | 2008-11-14 | 2008-11-14 | Method for preparing thermosensitive nano medicament carrier with dual-target magnetism and folacin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101411877A (en) |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101940791A (en) * | 2010-08-27 | 2011-01-12 | 天津医科大学 | Dually-targeted pH-sensitive antineoplastic drug carrier material as well as preparation and application thereof |
| WO2011020294A1 (en) * | 2009-08-17 | 2011-02-24 | 中国人民解放军军事医学科学院毒物药物研究所 | Magnetic nanoparticles having novel core-shell structure and ph responsiveness, and use thereof |
| CN102000350A (en) * | 2010-11-30 | 2011-04-06 | 厦门大学 | Folic acid receptor targeting type nano gold particles and preparation method thereof |
| CN102085375A (en) * | 2011-01-28 | 2011-06-08 | 同济大学 | In-situ magnetically-heated temperature-sensitive targeted nano drug carrier for reversal of multi-drug resistance in tumors |
| CN102166162A (en) * | 2011-01-31 | 2011-08-31 | 中山大学 | Tooth whitening complex with temperature sensitive magnetic targets and preparation and operation method thereof |
| CN101707109B (en) * | 2009-09-25 | 2011-10-05 | 南京邮电大学 | Functional superparamagnetic nano particle with uniform particle size and preparation method thereof |
| CN104087555A (en) * | 2014-07-16 | 2014-10-08 | 江苏东博生物医药有限公司 | Folic acid targeting magnetic color-developing nanoparticles and preparation method thereof |
| CN104109690A (en) * | 2014-06-19 | 2014-10-22 | 中山大学附属第一医院 | Functional nano gene transfer material and preparation method and application thereof |
| CN106310261A (en) * | 2016-10-21 | 2017-01-11 | 新乡医学院 | Preparation method of composite nano material with magnetism and folic acid double targeting |
| CN106421813A (en) * | 2016-10-21 | 2017-02-22 | 新乡医学院 | Drug-loaded nanoparticle with double targeting function and preparation method and application thereof |
| CN107375245A (en) * | 2017-07-21 | 2017-11-24 | 浙江理工大学 | A kind of polymer nano-particle preparation method of the load cancer therapy drug with excellent control-release function |
| CN107551271A (en) * | 2017-08-28 | 2018-01-09 | 上海长海医院 | A kind of dual intelligent targeted nano granules of magnetic ROS and preparation method thereof |
| CN108329442A (en) * | 2018-02-09 | 2018-07-27 | 西北工业大学 | A kind of CuO@PNIPAm temperature sensitive composite materials and preparation method |
-
2008
- 2008-11-14 CN CNA2008102027840A patent/CN101411877A/en active Pending
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011020294A1 (en) * | 2009-08-17 | 2011-02-24 | 中国人民解放军军事医学科学院毒物药物研究所 | Magnetic nanoparticles having novel core-shell structure and ph responsiveness, and use thereof |
| CN101707109B (en) * | 2009-09-25 | 2011-10-05 | 南京邮电大学 | Functional superparamagnetic nano particle with uniform particle size and preparation method thereof |
| CN101940791A (en) * | 2010-08-27 | 2011-01-12 | 天津医科大学 | Dually-targeted pH-sensitive antineoplastic drug carrier material as well as preparation and application thereof |
| CN102000350A (en) * | 2010-11-30 | 2011-04-06 | 厦门大学 | Folic acid receptor targeting type nano gold particles and preparation method thereof |
| CN102000350B (en) * | 2010-11-30 | 2012-08-15 | 厦门大学 | Folic acid receptor targeting type nano gold particles and preparation method thereof |
| CN102085375B (en) * | 2011-01-28 | 2012-12-05 | 同济大学 | In-situ magnetically-heated temperature-sensitive targeted nano drug carrier for reversal of multi-drug resistance in tumors |
| CN102085375A (en) * | 2011-01-28 | 2011-06-08 | 同济大学 | In-situ magnetically-heated temperature-sensitive targeted nano drug carrier for reversal of multi-drug resistance in tumors |
| CN102166162B (en) * | 2011-01-31 | 2016-08-03 | 中山大学 | There is teeth whitening complex and preparation, the operational approach of temperature sensitive magnetic target tropism |
| CN102166162A (en) * | 2011-01-31 | 2011-08-31 | 中山大学 | Tooth whitening complex with temperature sensitive magnetic targets and preparation and operation method thereof |
| CN104109690B (en) * | 2014-06-19 | 2017-04-26 | 中山大学附属第一医院 | Functional nano gene transfer material and preparation method and application thereof |
| CN104109690A (en) * | 2014-06-19 | 2014-10-22 | 中山大学附属第一医院 | Functional nano gene transfer material and preparation method and application thereof |
| CN104087555A (en) * | 2014-07-16 | 2014-10-08 | 江苏东博生物医药有限公司 | Folic acid targeting magnetic color-developing nanoparticles and preparation method thereof |
| CN106421813B (en) * | 2016-10-21 | 2019-07-26 | 新乡医学院 | Medicine-carried nano particles and its preparation method and application with dual-target function |
| CN106421813A (en) * | 2016-10-21 | 2017-02-22 | 新乡医学院 | Drug-loaded nanoparticle with double targeting function and preparation method and application thereof |
| CN106310261A (en) * | 2016-10-21 | 2017-01-11 | 新乡医学院 | Preparation method of composite nano material with magnetism and folic acid double targeting |
| CN106310261B (en) * | 2016-10-21 | 2019-10-01 | 新乡医学院 | Preparation method with magnetic and folic acid dual-target composite nano materials |
| CN107375245A (en) * | 2017-07-21 | 2017-11-24 | 浙江理工大学 | A kind of polymer nano-particle preparation method of the load cancer therapy drug with excellent control-release function |
| CN107375245B (en) * | 2017-07-21 | 2019-10-08 | 浙江理工大学 | A kind of polymer nano-particle preparation method of the load anticancer drug with excellent control-release function |
| CN107551271A (en) * | 2017-08-28 | 2018-01-09 | 上海长海医院 | A kind of dual intelligent targeted nano granules of magnetic ROS and preparation method thereof |
| CN108329442A (en) * | 2018-02-09 | 2018-07-27 | 西北工业大学 | A kind of CuO@PNIPAm temperature sensitive composite materials and preparation method |
| CN108329442B (en) * | 2018-02-09 | 2020-05-01 | 西北工业大学 | CuO @ PNIPAm temperature-sensitive composite material and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101411877A (en) | Method for preparing thermosensitive nano medicament carrier with dual-target magnetism and folacin | |
| Wang et al. | Microgels in biomaterials and nanomedicines | |
| Zheng et al. | pH and thermal dual-responsive nanoparticles for controlled drug delivery with high loading content | |
| Chang et al. | Thermo and pH dual responsive, polymer shell coated, magnetic mesoporous silica nanoparticles for controlled drug release | |
| Bysell et al. | Microgels and microcapsules in peptide and protein drug delivery | |
| Gui et al. | Encapsulating magnetic and fluorescent mesoporous silica into thermosensitive chitosan microspheres for cell imaging and controlled drug release in vitro | |
| CN102142310B (en) | Preparation method of nano magnetic polymer composite microspheres | |
| Gui et al. | Embedding fluorescent mesoporous silica nanoparticles into biocompatible nanogels for tumor cell imaging and thermo/pH-sensitive in vitro drug release | |
| CN103627004A (en) | Double-hydrophilic hyperbranched polymer, as well as preparation method and application thereof | |
| CN103254442B (en) | Disulfide bond linked polyester comb-type graft copolymer as well as preparation method and application thereof | |
| Liu et al. | Multilayer magnetic composite particles with functional polymer brushes as stabilizers for gold nanocolloids and their recyclable catalysis | |
| Tian et al. | Diselenide-crosslinked zwitterionic nanogels with dual redox-labile properties for controlled drug release | |
| CN103087257B (en) | Preparation method for pH and temperature dual-sensitive ion micro-hydrogel | |
| CN104436199A (en) | Preparation method of porous ferroferric oxide composite nanometre microspheres efficiently loaded with pharmorubicin | |
| CN1454924A (en) | Multifunctional organic-inorganic composite polymeric microball and preparing method thereof | |
| Han et al. | Dual responsive molecularly imprinted polymers based on UiO-66-DOX for selective targeting tumor cells and controlled drug release | |
| CN104958258A (en) | Substance-encapsulating vesicle and process for producing the same | |
| Richter et al. | Effect of pH, co-monomer content, and surfactant structure on the swelling behavior of microgel-azobenzene-containing surfactant complex | |
| Su et al. | Recent advances in applied fluorescent polymeric gels | |
| CN100573750C (en) | Double cladding water-based magnetofluid and preparation method thereof | |
| CN111249253A (en) | Preparation method of core-shell structure stimulus response type drug carrier and drug release method | |
| Sahiner et al. | 4-Vinylpyridine-based smart nanoparticles with N-isopropylacrylamide, 2-hydroxyethyl methacrylate, acrylic acid, and methacrylic acid for potential biomedical applications | |
| Sahiner et al. | Soft core-shell polymeric nanoparticles with magnetic property for potential guided drug delivery | |
| Talavat et al. | Thermodynamic computational calculations for preparation 5-fluorouracil magnetic moleculary imprinted polymers and their application in controlled drug release | |
| CN103386135A (en) | Preparation method of multifunctional medicine carrier integrating magnetism, fluorescence and thermosensitivity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Open date: 20090422 |