CN102580642A - Method for preparing high-magnetization chitosan nanospheres - Google Patents
Method for preparing high-magnetization chitosan nanospheres Download PDFInfo
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- CN102580642A CN102580642A CN201210060861XA CN201210060861A CN102580642A CN 102580642 A CN102580642 A CN 102580642A CN 201210060861X A CN201210060861X A CN 201210060861XA CN 201210060861 A CN201210060861 A CN 201210060861A CN 102580642 A CN102580642 A CN 102580642A
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Abstract
The invention provides a method for preparing high-magnetization chitosan nanospheres. according to the invention, an improved ultrasonic emulsification pre-crosslinking technique is adopted, namely, a chitosan solution in which superparamagnetic nanoparticles are dispersed is taken as a water phase, and liquid paraffin is taken as an oil phase, a high-magnetization and particle-size-controlled chitosan nanosphere is obtained through adjusting the composition of the oil and water phases and carrying out mixing, ultrasonic dispersion and ultrasonic pre-crosslinking,. The preparation method provided by the invention is simple, high in efficiency and low in cost; the highest saturation magnetization of the obtained chitosan nanosphere can be more than 45 emu/g; and the method has great application potentials in the fields of biological medicines, enzyme engineering and magnetic separation.
Description
Technical field
The invention belongs to nano meter biomaterial and field of pharmaceutical preparations, specifically is to adopt ultrasonic emulsification precrosslink legal system to be equipped with the method for the chitosan nano ball of the ultra paramagnetic nano particle of parcel.
Background technology
Magnetic macromolecular microsphere has important application prospects in fields such as cell separation purifying, enzyme immobilization, medicine conveying, biological detection, receives extensive concern (Adv Drug Deliv Rev, 2008,60:1252-1265 in recent years; Biomateria, 2005,26:3995-4021).Magnetic nano particles such as tri-iron tetroxide are assembled owing to attraction between the particle dipole easily, have limited its actual application value.For biocompatibility and the dispersion stabilization that improves superparamagnetic nanoparticle, adopt surfactant or macromolecular material that it is modified usually.Be divided into by the different magnetic macromolecular microspheres of structure: 1. shell/nuclear formula, outer shell is a macromolecular material, inner nuclear layer is a magnetic material; 2. nuclear/shell-type, outer shell is a magnetic material, inner nuclear layer is a macromolecular material; 3. shell/nuclear/shell-type, outer and internal layer is a macromolecular material, the intermediate layer is a magnetic material.Wherein with the research of first kind shell/nuclear formula polymer microsphere with use more.Macromolecular material commonly used comprises synthetic material (like polyethylene glycol, polystyrene, polymethyl methacrylate etc.) and natural macromolecular material (like shitosan, cellulose, starch etc.).Natural macromolecular material is owing to its biocompatibility biomedicine field fortunately is widely used, and wherein shitosan receives attention widely in recent years because its excellent biological compatibility, hypotoxicity, biodegradability and output are enriched.
The preparation method of shell/nuclear formula magnetic macromolecular microsphere mainly contains three kinds at present: investment, monomer polymerization method and in-situ method.Monomer polymerization comprise again suspension polymerisation, emulsion polymerisation, dispersin polymerization (biochemistry and biophysics progress, 2010,37:433-440).The magnetic particle wider distribution of investment preparation, out-of-shape and be difficult to control, in-situ polymerization is complicated, and the magnetic microsphere magnetic content that obtains is lower.Monomer polymerization method is a kind of common method for preparing magnetic macromolecular microsphere; Suspension polymerisation generally is used to prepare the micron order microballoon; Dispersin polymerization generally adopts artificial synthetic high polymer to prepare micron order to the nanoscale microballoon; But artificial synthetic high polymer is relatively poor aspect biocompatibility, has limited the biologic applications of magnetic nano-balls.People such as Shen (Colloids Surf B:Biointerfaces; 2009; 68:1-6) reported a kind of shitosan magnetic nanosphere that adopts emulsion polymerization to prepare the load 5-fluorouracil; Particle diameter 100 ± 20nm, but the specific saturation magnetization of this nanosphere has only 3.4emu/g, in practical application, has the not strong problem of magnetic responsiveness.
The present invention adopts a kind of improved ultrasonic emulsification cross-linking method, with tri-iron tetroxide (Fe
3O
4) nano particle is for examining, shitosan is a shell, obtains a kind of magnetic content height through changing reaction condition, the shitosan magnetic nanosphere of particle size range controlled (100-1000nm) has potential using value at technical field of bioengineering.
Summary of the invention
The present invention is intended to overcome the prior art deficiency, provides a kind of simple to operate, the preparation method of the shitosan magnetic nanosphere that the scale that is easy to is amplified, and the nanosphere particle diameter that this method obtains is controlled, and good biocompatibility can be widely used in biotechnology and field of medicaments.
The technology path that the present invention takes is:
1. prepare superparamagnetism Fe through chemical coprecipitation
3O
4Nano particle further adopts natrium citricum to modify and makes water-based magnetic fluid.
2. get that water-based magnetic fluid mixes as water with chitosan-acetic acid solution in an amount of step 1, slowly inject the oil phase that is added with surfactant after ultrasonic 10 minutes, mechanical agitation is more than 15 minutes under given pace.
The emulsion that obtains in the step 2 is further ultrasonic in ultrasonic cell disruption instrument 3., in ultrasonic, drip crosslinking agent precrosslink, stop ultrasonic after a period of time.After the gained emulsion continued to stir a period of time at a certain temperature, use benzinum, isopropyl alcohol, second alcohol and water centrifuge washing successively, promptly get target product.For the ease of storing, also can adopt freeze-drying to obtain chitosan magnetic nanosphere powder.
The present invention is applicable to preparation nanoscale (100-1000nm) magnetic microsphere.Used macromolecular material is a shitosan, but is not limited to shitosan, can also be other natural polysaccharides such as glucan, starch, cellulose etc.
Superparamagnetism Fe in the step 1 of the present invention
3O
4Nano particle is self-control, particle size range 9.6-22.4nm.But be not limited to Fe
3O
4, can also be MnFe
2O
4, γ-Fe
2O
3Etc. ultra paramagnetic nano particle.
Fe in the step 2 of the present invention
3O
4Nano particle and chitosan mass are than scope 1; 1～1; 4, the chitosan molecule weight range is 5000-1,000,000 ten thousand, and used oil phase can be atoleine, castor oil, olive oil, soybean wet goods, or the mixture of they and benzinum.Optimum condition is Fe
3O
4Nano particle and chitosan mass are than 1; 1, chitosan molecule amount 5000, oil phase is an atoleine.
Ultrasonic cell disruption instrument ultrasonic power scope 100w-800W in the step 3 of the present invention, 25-50 ℃ of cross-linking reaction temperature range, cross-linking reaction time 6-24 hour.Optimum condition is: ultrasonic power 500W, 40 ℃ of cross-linking reaction temperature, cross-linking reaction time 12 hours.
Technology path 3 among the present invention is committed steps; Its characteristics are to add crosslinking agent in the ultrasonic dispersion process; Make nanosphere carry out precrosslink earlier, precrosslink time range 10min-60min helps to keep the sphericity and the high magnetic content of chitosan nano ball like this; Conventional method chitosan sphere degree difference or not balling-up have been avoided, the shortcoming that coated magnetic nanoparticle is few.Again through the further crosslinked good nanosphere of sphericity that just can obtain in the later stage whipping process.
The technique effect that the present invention produces:
The invention provides the crosslinked method for preparing the chitosan magnetic nanosphere of a kind of ultrasonic emulsification.Fe
3O
4But nano particle both can have been bought also laboratory self-control, and the particle diameter of nanosphere can be controlled through changing conditions such as ultrasonic power, chitosan molecule amount and oil phase viscosity, good reproducibility, and the preparation method is simple, and efficient is high, and cost is low.The saturation magnetization of gained shitosan magnetic nanosphere reaches as high as more than the 45emu/g.Having at biological medicine, enzyme engineering, magnetic separation field very greatly should be potential.
Description of drawings
Fig. 1 is transmission electron microscope (TEM) photo of the shitosan magnetic nanosphere of embodiment 1 preparation
The specific embodiment
Embodiment one
(Mw 5 2% shitosan; 000) the nano ferriferrous oxide particle aqueous solution 1ml of acetum 1ml and 10mg/ml mixes; Ultrasonic 30 minutes, slowly be added drop-wise in the atoleine that contains 4%Span80 at certain following above-mentioned solution of stir speed (S.S.) then, continue to stir 15 minutes.With the colostric fluid that obtains in ultrasonic cell disruption instrument ultrasonic 30 minutes, power 500W dripped the 4ml glutaraldehyde solution after ultrasonic 15 minutes, and it is tentatively crosslinked that the chitosan nano ball is carried out.After the ultrasonic end preliminary crosslinked emulsion is transferred in the there-necked flask, under agitation continued 40 ℃ of temperature crosslinked 12 hours.Reaction is used benzinum, isopropyl alcohol, ethanol and pure water centrifuge washing after finishing successively, promptly obtains wrapping up Fe
3O
4The chitosan magnetic nano particle, average grain diameter 174nm (figure one).
Embodiment two
(Mw 50 2% shitosan; 000) the nano ferriferrous oxide particle aqueous solution 1ml of acetum 1ml and 20mg/ml mixes; Ultrasonic 30 minutes, slowly be added drop-wise in the atoleine that contains 4%Span80 at certain following above-mentioned solution of stir speed (S.S.) then, continue to stir 15 minutes.With the colostric fluid that obtains in ultrasonic cell disruption instrument ultrasonic 30 minutes, power 400W dripped the 4ml glutaraldehyde solution after ultrasonic 15 minutes, and it is tentatively crosslinked that the chitosan nano ball is carried out.After the ultrasonic end preliminary crosslinked emulsion is transferred in the there-necked flask, under agitation continued 50 ℃ of temperature crosslinked 12 hours.Reaction is used benzinum, isopropyl alcohol, ethanol and pure water centrifuge washing after finishing successively, promptly obtains the chitosan magnetic nano particle, average grain diameter 360nm.
Embodiment three
(Mw 200 2% shitosan; 000) the nano ferriferrous oxide particle aqueous solution 1ml of acetum 1ml and 15mg/ml mixes; Ultrasonic 30 minutes; Slowly be added drop-wise in the olive oil/benzinum (volume ratio 8/2) that contains 4%Span80 at certain following above-mentioned solution of stir speed (S.S.) then, continue to stir 15 minutes.With the colostric fluid that obtains in ultrasonic cell disruption instrument ultrasonic 30 minutes, power 500W dripped the 4ml glutaraldehyde solution after ultrasonic 15 minutes, and it is tentatively crosslinked that the chitosan nano ball is carried out.After the ultrasonic end preliminary crosslinked emulsion is transferred in the there-necked flask, under agitation continued 40 ℃ of temperature crosslinked 24 hours.Reaction is used benzinum, isopropyl alcohol, ethanol and pure water centrifuge washing after finishing successively, promptly obtains the chitosan magnetic nano particle, average grain diameter 870nm.
Claims (8)
1. method for preparing high magnetic content chitosan nano ball.It is characterized in that, be water with the chitosan solution that is dispersed with ultra paramagnetic nano particle, adopts a kind of improved ultrasonic emulsification cross-linking method; Through regulating the profit phase composition; By stirring and ultrasonic dispersion, be aided with ultrasonic precrosslink, obtain a kind of magnetic content height, the controlled chitosan nano ball of particle diameter.
2. method according to claim 1 is characterized in that described magnetic nano-particle has superparamagnetism, and composition can be Fe
3O
4, MnFe
2O
4, γ-Fe
2O
3Deng, particle diameter is less than 30nm.
3. method according to claim 1 is characterized in that, described chitosan molecule weight range is 5k-1000K, is preferably 5k-200k.
4. method according to claim 1 is characterized in that described oil phase is not limited to atoleine, can also be the mixture of olive oil, soybean oil, castor oil and they and benzinum.
5. method according to claim 1 is characterized in that, profit phase volume ratio scope is 100: 1-20: 1, be preferably 50: 1-30: 1.
6. method according to claim 1 is characterized in that the power bracket of ultrasonic cell disruption instrument is 100W-800W, is preferably 300W-500W.The mechanical agitation speed range is 100-2000rpm, preferred 300-800rpm.
7. method according to claim 1 is characterized in that, ultrasonic precrosslink time range 10-120 minute is preferably 30-60 minute.
8. method according to claim 1 is characterized in that, the crosslinking temperature scope is 25-50 ℃ after the mechanical agitation, is preferably 40-45 ℃, back crosslinking time 6-24 hour, is preferably 12 hours.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103824671A (en) * | 2014-03-12 | 2014-05-28 | 中国石油大学(华东) | Nano magnetic fluid for monitoring fracturing crack and preparing method of nano magnetic fluid |
| CN104258822A (en) * | 2014-10-22 | 2015-01-07 | 天津工业大学 | Chitosan and chitosan quaternary ammonium salt composite magnetic microsphere and preparation method thereof |
| CN104622845A (en) * | 2015-01-02 | 2015-05-20 | 吉林大学 | Preparation method of chitosan microcapsules containing magnetic nano particles inside |
| CN105294908A (en) * | 2015-11-20 | 2016-02-03 | 云南健牛生物科技有限公司 | Synthesis method and applications of magnetic nano high-molecular polymer |
| CN114573038A (en) * | 2022-03-21 | 2022-06-03 | 同济大学 | Granular magnetic drive micro motor and magnetic control preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101748113A (en) * | 2009-11-26 | 2010-06-23 | 黑龙江八一农垦大学 | Method for preparing immobilized glucose isomerase with composite magnetic chitosan microballoon spheres |
| CN101831031A (en) * | 2010-05-12 | 2010-09-15 | 东华大学 | Acrylamide copolymer containing halothane and phosphoric acid ester as well as preparation method and application thereof |
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2012
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101748113A (en) * | 2009-11-26 | 2010-06-23 | 黑龙江八一农垦大学 | Method for preparing immobilized glucose isomerase with composite magnetic chitosan microballoon spheres |
| CN101831031A (en) * | 2010-05-12 | 2010-09-15 | 东华大学 | Acrylamide copolymer containing halothane and phosphoric acid ester as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 鲍世韵等: "卡铂碳包铁纳米壳聚糖微球的制备和特征", 《中国现代应用药物杂志》 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103824671A (en) * | 2014-03-12 | 2014-05-28 | 中国石油大学(华东) | Nano magnetic fluid for monitoring fracturing crack and preparing method of nano magnetic fluid |
| CN103824671B (en) * | 2014-03-12 | 2016-07-06 | 中国石油大学(华东) | A kind of nanometer magnetofluid for induced fracture monitoring and preparation method thereof |
| CN104258822A (en) * | 2014-10-22 | 2015-01-07 | 天津工业大学 | Chitosan and chitosan quaternary ammonium salt composite magnetic microsphere and preparation method thereof |
| CN104258822B (en) * | 2014-10-22 | 2016-05-11 | 天津工业大学 | Shitosan and chitosan quaternary ammonium salt composite magnetic microballoon and preparation method |
| CN104622845A (en) * | 2015-01-02 | 2015-05-20 | 吉林大学 | Preparation method of chitosan microcapsules containing magnetic nano particles inside |
| CN105294908A (en) * | 2015-11-20 | 2016-02-03 | 云南健牛生物科技有限公司 | Synthesis method and applications of magnetic nano high-molecular polymer |
| CN114573038A (en) * | 2022-03-21 | 2022-06-03 | 同济大学 | Granular magnetic drive micro motor and magnetic control preparation method thereof |
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|---|---|
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Effective date of registration: 20221025 Address after: 255214 Liangzhuang Sanquan mountain, Chengdong sub district office, Boshan District, Zibo City, Shandong Province Patentee after: ZIBO KANGBEI MEDICAL DEVICES Co.,Ltd. Address before: 266580 No. 66 Changjiang West Road, Qingdao economic and Technological Development Zone, Shandong Patentee before: CHINA University OF PETROLEUM (EAST CHINA) |