CN103041409A - Preparation method of pH and thermal dual-sensitive lipidosome loaded with magnetic carbon quantum dots on internal water phase - Google Patents
Preparation method of pH and thermal dual-sensitive lipidosome loaded with magnetic carbon quantum dots on internal water phase Download PDFInfo
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Abstract
The invention relates to a preparation method of pH and thermal dual-sensitive lipidosome loaded with magnetic carbon quantum dots on an internal water phase, which concretely comprises the following steps of: 1) preparing nano ferroferric oxide by a co-precipitation method, carrying out surface modification by polyethyleneimine, preparing carbon quantum dots by a microwave pyrolysis method, and adding the carbon quantum dots into the modified magnetic particle solution to form the magnetic carbon quantum dots; and 2) loading the magnetic carbon quantum dots into the internal water phase of the lipidosome by a low-pressure film formation-high-pressure incubation method, and grafting the pH and heat sensitivity triblock copolymer on the surface of the lipidosome by hydrophobic effect to prepare the lipidosome modified by nano particles and polymer. Compared with the prior art, the preparation method is simple and lower in cost; the prepared product can be developed into a diagnosis therapeutic agent with functions of magnetic targeting, fluorescence imaging or tracing; and the medicine carrying system of pH and thermal controlled-release medicine has important reference value for developing other types of multifunctional medicine carriers.
Description
Technical field
The invention belongs to biomaterial and nanometer medicine technical field, be specifically related to the pH of interior water carried magnetic carbon quantum dot and the preparation method of hot Lazer's property liposome.
Background technology
Liposome refers to that by phospholipid be the vesicle that film material and additives form, and has similar biomembranous bilayer structure, can seal water solublity and fat-soluble medicine in capsule and becomes a kind of novel pharmaceutical carrier.The solvent of liposome---phospholipid is the proper constituent of organism, can degrade avirulence and immunogenicity through biotransformation in vivo.In view of it has the raising medicine stability, reduce drug dose, reduce toxicity, alleviate immunoreation, delay to discharge, reduce digestion rate in the body, change the advantages such as medicine distributes in vivo, liposome is considered at present one of pharmaceutical carrier of tool development prospect, can be widely used in the clinical treatment of tumor, infectious disease, cardiovascular disease and dermatosis etc.
Semiconductor-quantum-point (such as CdSe, CdS, InAs etc.) presents growing trend because of its unique optical property application in modern biotechnology, but the defective of its existence is also fairly obvious, harsh such as synthesis condition, cost is higher, have bio-toxicity and environmental hazard etc., limited the application in life sciences.At present, carbon source material is synthesized in a large number, and shown in a lot of fields using value as high performance material, especially be similar to semi-conductive luminous carbon quantum dot, one comes out, namely with advantages such as its good optical property, synthetic convenience, abundant raw material and toxicity are little, be applied to the bio-science fields such as fluorescent labeling, imaging, sensing.
Modify by the liposome phospholipid bilayer being carried out functional polymer (such as pH and hot Lazer's property block copolymer), then inorganic nanoparticles (such as nanometer gold, ferrum oxide, quantum dot etc.) load is entered in the interior water and bilayer of liposome, obtain a kind of lipidosome drug carrier of multifunction.The composite system of this novel liposome-nano-particle can be used for optics, magnetic resonance, surface plasma resonance imaging, and the fields such as the fluorescent labeling of active somatic cell and tissue and spike show huge application prospect.
In recent years, the related work person is devoted to develop the research of multi-functional lipidosome drug carrier always, especially aspect liposome-nano-particle complex, obtained successively a series of progress, the correlational study achievement (for example has been published on the internal authority periodical; Al-Jamal W.T., Kostarelos K.Liposome-nanoparticlehybrids for multifunctional diagnostic and therapeutic application.Nanomedicine.2007,2,85~98.; Xie J., Huang J., Li X., Sun S., Chen X.Iron oxide nanoparticle platform forbiomedical applications.Curr.Med.Chem.2009,16,1278~1294.; Smith A.M., Nie S.Semiconductor nanocrystals:structure, properties, and band gap engineering.Acc.Chem.Res.2009,43,190~200.; Pan J., Wan D., Gong J.PEGylated liposome coated QDs/mesoporous silica core-shell nanoparticles for molecular imaging.Chem.Commun.2011,47,3442~3444.).
So far, the existing Chinese patent report of the preparation method of relevant multi-functional lipidosome drug carrier.For example, it is film that the employing film dispersion methods such as Chu Maoquan are made lipid, and then quantum dot adds ethyl orthosilicate for the liposome of nuclear, form silicon dioxide at surface of liposome, make the silicon dioxide microsphere (publication number: CN101362066A) of liposome embedded quantum dots.He Rong etc. are dispersed in alcohol liposome inside with water solublity semiconductor-quantum-point and 5-fluorouracil, adopt the thin film extruder respectively by polycarbonate membrane, have prepared nano alcohol liposome (publication number: CN101327189A).Chang Jin etc. carry quantum dot and cancer therapy drug with the inner bag of Poly(D,L-lactide-co-glycolide microsphere, the outside coats the cation high molecular liposome that lysine/chitosan/octadecyl quaternary ammonium salt/cholesterol is prepared from, and makes a kind of drug carried microsphere system (publication number: CN102525941A) of core/shell structure.
Although related to the preparation method of the functionalization liposome of load quantum dot in above document and the patent, but some crucial technical problem still needs to be resolved hurrily, such as complicated process of preparation, and the toxicity of quantum dot, liposome multi-functional, and the controllability of drug release etc.Therefore, develop a kind of prepare simple, cost is low, the liposome of multifunction, for the basic research of development high-quality pharmaceutical carrier and use finally all that tool is of great significance.Up to now, there is not yet the liposome that pH and hot Lazer's property polymer surfaces are modified, water load carbon quantum dot in the Hydrothermal Synthesis/nano ferriferrous oxide composite particles, and the relevant Chinese patent report with the Multifunction liposome that integrates fluorescence, magnetic, pH and heat sensitivity.
Summary of the invention
Purpose of the present invention is exactly to provide a kind of method simple for the defective that overcomes above-mentioned prior art existence, the pH of the interior water carried magnetic carbon quantum dot quick, that cost is low and the preparation method of hot Lazer's property liposome.
Purpose of the present invention can be achieved through the following technical solutions: a kind of pH of interior water carried magnetic carbon quantum dot and the preparation method of hot Lazer's property liposome is characterized in that the method specifically may further comprise the steps:
(1) dissolving iron chloride, ferrous sulfate and thioglycolic acid formation homogenizing aqueous solution to a large amount of black particles occurring, are nano ferriferrous oxide in alkali condition and 65 ℃ of lower reactions; Under ultrasonication, dropwise add polymine, form the magnetic nano particle of positively charged;
(2) glucose and Polyethylene Glycol are dissolved in the deionized water, change microwave reactor reaction a period of time over to, make the water-soluble carbon quantum dot solution; Under ultrasonication, the carbon quantum dot solution is dropwise added in the magnetic nano particle system that step (1) obtains, form magnetic carbon quantum dot composite particles by Electrostatic Absorption;
(3) polyacrylic acid PAA, dodecyl amine DDA and cross-linking agent I are dissolved in the organic solvent I, at certain temperature I carboxylic-amine reaction occuring generates the PAA-DDA graft polymers, this polymer, NIPA NIPAM and cross-linking agent II are dissolved in the organic solvent II, at certain temperature II polymerization reaction take place, generate PNIPAM-PAA-DDA triblock copolymer PNAD;
(4) lecithin, cholesterol, PNAD are dissolved in the mixed liquor of chloroform/methanol with certain mass ratio, evacuation in Rotary Evaporators makes the solvent rear film forming of volatilizing fully, adds deionized water, under magnetic agitation, film is come off, make the liposome suspension;
(5) step (4) gained liposome suspension is put into the autoclave that places water bath with thermostatic control with step (2) gained composite particles aqueous solution, pass into carbon dioxide, under certain temperature and pressure, stir hatching; Hatching is cooled to room temperature after finishing, and slowly carbon dioxide gas namely gets the target liposome solutions.
Iron chloride described in the step (1), ferrous sulfate and thioglycolic acid concentration ratio are 1: 1: 2~5: 1: 6, alkali condition is pH7~8, magnetic nano particle is of a size of 10~30nm, and the addition of polymine is 0.1~0.5% of described homogenizing aqueous solution quality.
Glucose sugar described in the step (2) is 1~5 with the mass volume ratio of Polyethylene Glycol: 5~25g/mL, the microwave power of described microwave reactor are 540W, and the response time is 1~10min.
PNIPAM, PAA, DDA monomer mole ratio are 94: 1: 5~79: 1: 20 among the PNIPAM-PAA-DDA triblock copolymer PNAD described in the step (3), cross-linking agent I is dicyclohexylcarbodiimide DDC, organic solvent I is N, N '-dimethyl formamide DMF, temperature I is 20~90 ℃, and cross-linking agent II is azodiisobutyronitrile AIBN, and organic solvent II is 1,4-dioxane, temperature II are 50~80 ℃.
The mass ratio of lecithin described in the step (4), cholesterol, PNAD is 1: 1: 1~5: 1: 0.1, and the volume ratio of chloroform/methanol is 1: 1~3: 1, and the rotary evaporation temperature is 35~45 ℃.
The mass ratio of the composite particles aqueous solution described in the step (5) and liposome suspension is 1: 5~1: 10, and bath temperature is 40~50 ℃, and setting pressure is 10~30MPa, and the stirring brooding time is 20~50min.
Effect of the present invention is: the composite particles of selecting low toxicity carbon quantum dot and super-paramagnetic ferriferrous oxide is the function nano grain, the block polymer decorated liposome of pH and hot Lazer's property is carrier, be written into the function nano grain at interior aqueous phase, make the Multifunction liposome that integrates fluorescence, magnetic, pH and thermal sensitivity.Compared with prior art, the inventive method is simple, cost is lower, the multi-functional liposome of preparation can develop into has the magnetic targeting, the diagnoses and treatment agent of fluorescence imaging or tracking function, the medicine-carried system of pH and hot controlled release drug has important reference value for the multi-functional drug carriers that develops other type.
Description of drawings
Fig. 1 is the structural representation of multi-functional liposome;
Fig. 2 is uv-visible absorption spectra and the fluorescence emission spectrum of multi-functional liposome;
Fig. 3 is the hysteresis curve of multi-functional liposome;
Fig. 4 is the relation curve that the size of multi-functional liposome changes with pH value of solution;
Fig. 5 is the relation curve that the absorbance of multi-functional liposome changes with solution temperature.
The specific embodiment
The present invention is described in detail below in conjunction with the drawings and specific embodiments.
Embodiment 1
The pH of interior water carried magnetic carbon quantum dot and the structure of hot Lazer's property liposome are as shown in Figure 1, detailed preparation process is as follows: under quick magnetic agitation, the DMF solution that is dissolved with 1mol DDC is dropwise added in the 10mL DMF solution that is dissolved with 0.1mol PAA and 1mol DDA, form mixed solution, then at 60 ℃ of lower reaction 24h, obtain PAA carboxyl percent grafting and be 20% polymer P AA-DDA.Next, take by weighing 90mgNIPAM, 10mg PAA-DDA and 5mgAIBN and be dissolved in Isosorbide-5-Nitrae-dioxane, make PNIPAM-PAA-DDA triblock copolymer PNAD at 70 ℃ of lower reaction 12h.
0.2mol iron chloride, 0.1mol ferrous sulfate and 0.3mol thioglycolic acid are dissolved in the 100mL deionized water, regulating pH of mixed is 7.5, in magnetic agitation and 65 ℃ of lower reactions, make a large amount of black ferroferric oxide nanoparticles, dripping polymine to mass fraction is 0.1%.With changing microwave reactor over to behind the 5mL Polyethylene Glycol PEG-200 dissolving 1g glucose, under 540W power, react 5min, make the carbon quantum dot, then it is dropped in the magnetic particle solution, under ultrasonication, form the magnetic particle of carbon quantum dot surface adsorption.
Take by weighing 200mg lecithin, 100mg cholesterol, 50mg PNAD and be dissolved in 50mL chloroform/methanol (2/1) mixed liquor, be evaporated to film forming 41 ℃ of lower rotations.Adding 5mL water under magnetic agitation comes off film, form suspension, add 2g magnetic carbon quantum dot solution, place the autoclave of 40 ℃ of waters bath with thermostatic control, pass into carbon dioxide, keeping the still internal pressure is 15MPa, hatching 30min, be cooled at last room temperature, discharge gas reactor, obtain pH and hot Lazer's property liposome solutions of interior water carried magnetic carbon quantum dot.
Adopt ultraviolet-visible spectrophotometer and spectrofluorophotometer to measure respectively uv-visible absorption spectra and the fluorescence emission spectrum (as shown in Figure 2) of liposome, adopt vibration sample gaussmeter to measure the hysteresis curve (as shown in Figure 3) of liposome, the relation curve (as shown in Figure 4) that the hydrodynamics size that adopts dynamic light scattering to measure liposome changes with system pH adopts ultraviolet-visible spectrophotometer to measure the absorbance of liposome with the relation curve (as shown in Figure 5) of system variations in temperature.
Embodiment 2
Under quick magnetic agitation, the DMF solution that is dissolved with 1mol DDC is dropwise added in the 10mLDMF solution that is dissolved with 0.1mol PAA and 1.5mol DDA, form mixed solution, then at 70 ℃ of lower reaction 24h, obtain PAA carboxyl percent grafting and be 30% polymer P AA-DDA.Next, take by weighing 85mg NIPAM, 15mgPAA-DDA and 5mg AIBN is dissolved in Isosorbide-5-Nitrae-dioxane, make PNIPAM-PAA-DDA triblock copolymer PNAD at 70 ℃ of lower reaction 12h.
0.1mol iron chloride, 0.05mol ferrous sulfate and 0.15mol thioglycolic acid are dissolved in the 100mL deionized water, regulating pH of mixed is 7.5, in magnetic agitation and 65 ℃ of lower reactions, make a large amount of black ferroferric oxide nanoparticles, dripping polymine to mass fraction is 0.1%.With changing microwave reactor over to behind the 10mLPEG-200 dissolving 2g glucose, under 540W power, react 5min, make the carbon quantum dot, then it is dropped in the magnetic particle solution, under ultrasonication, form the magnetic particle of carbon quantum dot surface adsorption.
Take by weighing 100mg lecithin, 50mg cholesterol, 25mg PNAD and be dissolved in 25mL chloroform/methanol (2/1) mixed liquor, be evaporated to film forming 41 ℃ of lower rotations.Adding 5mL water under magnetic agitation comes off film, form suspension, add 1g magnetic carbon quantum dot solution, place the autoclave of 40 ℃ of waters bath with thermostatic control, pass into carbon dioxide, keeping the still internal pressure is 20MPa, hatching 30min, be cooled at last room temperature, discharge gas reactor, obtain pH and hot Lazer's property liposome solutions of interior water carried magnetic carbon quantum dot.The characterizing method of liposome is with embodiment 1.
Embodiment 3
Under quick magnetic agitation, the DMF solution that is dissolved with 1mol DDC is dropwise added in the 10mLDMF solution that is dissolved with 0.1mol PAA and 2.0mol DDA, form mixed solution, then at 70 ℃ of lower reaction 24h, obtain PAA carboxyl percent grafting and be 40% polymer P AA-DDA.Next, take by weighing 85mg NIPAM, 15mg PAA-DDA and 10mgAIBN and be dissolved in Isosorbide-5-Nitrae-dioxane, make PNIPAM-PAA-DDA triblock copolymer PNAD at 70 ℃ of lower reaction 12h.
0.1mol iron chloride, 0.05mol ferrous sulfate and 0.15mol thioglycolic acid are dissolved in the 100mL deionized water, regulating pH of mixed is 7.5, in magnetic agitation and 65 ℃ of lower reactions, make a large amount of black ferroferric oxide nanoparticles, dripping polymine to mass fraction is 0.1%.With changing microwave reactor over to behind the 15mL PEG-200 dissolving 3g glucose, under 540W power, react 5min, make the carbon quantum dot, then it is dropped in the magnetic particle solution, under ultrasonication, form the magnetic particle of carbon quantum dot surface adsorption.
Take by weighing 100mg lecithin, 50mg cholesterol, 25mg PNAD and be dissolved in 25mL chloroform/methanol (2/1) mixed liquor, be evaporated to film forming 41 ℃ of lower rotations.Adding 5mL water under magnetic agitation comes off film, form suspension, add 1g magnetic carbon quantum dot solution, place the autoclave of 40 ℃ of waters bath with thermostatic control, pass into carbon dioxide, keeping the still internal pressure is 25MPa, hatching 30min, be cooled at last room temperature, discharge gas reactor, obtain pH and hot Lazer's property liposome solutions of interior water carried magnetic carbon quantum dot.The characterizing method of liposome is with embodiment 1.
Embodiment 4
Under quick magnetic agitation, the DMF solution that is dissolved with 1mol DDC is dropwise added in the 10mL DMF solution that is dissolved with 0.1mol PAA and 0.5mol DDA, form mixed solution, then at 70 ℃ of lower reaction 24h, obtain PAA carboxyl percent grafting and be 10% polymer P AA-DDA.Next, take by weighing 80mg NIPAM, 20mgPAA-DDA and 5mg AIBN is dissolved in Isosorbide-5-Nitrae-dioxane, make PNIPAM-PAA-DDA triblock copolymer PNAD at 70 ℃ of lower reaction 12h.
0.3mol iron chloride, 0.15mol ferrous sulfate and 0.45mol thioglycolic acid are dissolved in the 100mL deionized water, regulating pH of mixed is 7.5, in magnetic agitation and 65 ℃ of lower reactions, make a large amount of black ferroferric oxide nanoparticles, dripping polymine to mass fraction is 0.1%.With changing microwave reactor over to behind the 20mL PEG-200 dissolving 4g glucose, under 540W power, react 5min, make the carbon quantum dot, then it is dropped in the magnetic particle solution, under ultrasonication, form the magnetic particle of carbon quantum dot surface adsorption.
Take by weighing 50mg lecithin, 25mg cholesterol, 15mg PNAD and be dissolved in 20mL chloroform/methanol (2/1) mixed liquor, be evaporated to film forming 41 ℃ of lower rotations.Adding 5mL water under magnetic agitation comes off film, form suspension, add 0.5g magnetic carbon quantum dot solution, place the autoclave of 40 ℃ of waters bath with thermostatic control, pass into carbon dioxide, keeping the still internal pressure is 30MPa, hatching 30min, be cooled at last room temperature, discharge gas reactor, obtain pH and hot Lazer's property liposome solutions of interior water carried magnetic carbon quantum dot.The characterizing method of liposome is with embodiment 1.
Embodiment 5
A kind of pH of interior water carried magnetic carbon quantum dot and the preparation method of hot Lazer's property liposome is characterized in that the method specifically may further comprise the steps:
(1) dissolving iron chloride, ferrous sulfate and thioglycolic acid form the homogenizing aqueous solution, wherein iron chloride, ferrous sulfate and thioglycolic acid concentration ratio are 1: 1: 2, regulate the pH7 of aqueous solution, to a large amount of black particles occurring, be nano ferriferrous oxide 65 ℃ of lower reactions; Dropwise add polymine under ultrasonication, the addition of polymine is 0.1% of described homogenizing aqueous solution quality, forms the magnetic nano particle of positively charged;
(2) glucose and Polyethylene Glycol are 1 by mass volume ratio: 5g/mL is dissolved in the deionized water, changes microwave reactor reaction 1min over to, and the microwave power of microwave reactor is 540W, makes the water-soluble carbon quantum dot solution; Under ultrasonication, the carbon quantum dot solution is dropwise added in the magnetic nano particle system that step (1) obtains, form magnetic carbon quantum dot composite particles by Electrostatic Absorption;
(3) polyacrylic acid PAA, dodecyl amine DDA and DDC are dissolved among the DMF, at 20 ℃ carboxylic-amine reaction occuring generates the PAA-DDA graft polymers, this polymer, NIPA NIPAM and AIBN are dissolved in 1, in the 4-dioxane, at 50 ℃ of polymerization reaction take places, generate PNIPAM-PAA-DDA triblock copolymer PNAD, PNIPAM, PAA, DDA monomer mole ratio are 94: 1: 5 among the gained PNIPAM-PAA-DDA triblock copolymer PNAD
(4) lecithin, cholesterol, PNAD were dissolved in the mixed liquor (volume ratio of chloroform/methanol was as 1: 1) of chloroform/methanol as 1: 1: 1 take mass ratio, evacuation in Rotary Evaporators, the rotary evaporation temperature is 35 ℃, make the solvent rear film forming of volatilizing fully, add deionized water, under magnetic agitation, film is come off, make the liposome suspension;
(5) be to put into the autoclave of the water bath with thermostatic control that places 40 ℃ at 1: 5 with step (4) gained liposome suspension in mass ratio with step (2) gained composite particles aqueous solution, pass into carbon dioxide, under 40 ℃ and 10MPa pressure, stir hatching 20min; Hatching is cooled to room temperature after finishing, and slowly carbon dioxide gas namely gets the target liposome solutions.
Embodiment 6
A kind of pH of interior water carried magnetic carbon quantum dot and the preparation method of hot Lazer's property liposome is characterized in that the method specifically may further comprise the steps:
(1) dissolving iron chloride, ferrous sulfate and thioglycolic acid form the homogenizing aqueous solution, wherein iron chloride, ferrous sulfate and thioglycolic acid concentration ratio are 5: 1: 6, regulate the pH8 of aqueous solution, to a large amount of black particles occurring, be nano ferriferrous oxide 65 ℃ of lower reactions; Dropwise add polymine under ultrasonication, the addition of polymine is 0.5% of described homogenizing aqueous solution quality, forms the magnetic nano particle of positively charged;
(2) glucose and Polyethylene Glycol are that 5~25g/mL is dissolved in the deionized water by mass volume ratio, change microwave reactor reaction 10min over to, and the microwave power of microwave reactor is 540W, makes the water-soluble carbon quantum dot solution; Under ultrasonication, the carbon quantum dot solution is dropwise added in the magnetic nano particle system that step (1) obtains, form magnetic carbon quantum dot composite particles by Electrostatic Absorption;
(3) polyacrylic acid PAA, dodecyl amine DDA and DDC are dissolved among the DMF, at 90 ℃ carboxylic-amine reaction occuring generates the PAA-DDA graft polymers, this polymer, NIPA NIPAM and AIBN are dissolved in 1, in the 4-dioxane, at 80 ℃ of polymerization reaction take places, generate PNIPAM-PAA-DDA triblock copolymer PNAD, PNIPAM, PAA, DDA monomer mole ratio are 79: 1: 20 among the gained PNIPAM-PAA-DDA triblock copolymer PNAD
(4) lecithin, cholesterol, PNAD were dissolved in the mixed liquor (volume ratio of chloroform/methanol was as 3: 1) of chloroform/methanol as 5: 1: 0.1 take mass ratio, evacuation in Rotary Evaporators, the rotary evaporation temperature is 35~45 ℃, make the solvent rear film forming of volatilizing fully, add deionized water, under magnetic agitation, film is come off, make the liposome suspension;
(5) be to put into the autoclave of the water bath with thermostatic control that places 50 ℃ at 1: 10 with step (4) gained liposome suspension in mass ratio with step (2) gained composite particles aqueous solution, pass into carbon dioxide, under 50 ℃ and 30MPa pressure, stir hatching 50min; Hatching is cooled to room temperature after finishing, and slowly carbon dioxide gas namely gets the target liposome solutions.
The above only is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.
Claims (6)
1. the pH of water carried magnetic carbon quantum dot and the preparation method of hot Lazer's property liposome in one kind is characterized in that the method specifically may further comprise the steps:
(1) dissolving iron chloride, ferrous sulfate and thioglycolic acid formation homogenizing aqueous solution to a large amount of black particles occurring, are nano ferriferrous oxide in alkali condition and 65 ℃ of lower reactions; Under ultrasonication, dropwise add polymine, form the magnetic nano particle of positively charged;
(2) glucose and Polyethylene Glycol are dissolved in the deionized water, change microwave reactor reaction a period of time over to, make the water-soluble carbon quantum dot solution; Under ultrasonication, the carbon quantum dot solution is dropwise added in the magnetic nano particle system that step (1) obtains, form magnetic carbon quantum dot composite particles by Electrostatic Absorption;
(3) polyacrylic acid PAA, dodecyl amine DDA and cross-linking agent I are dissolved in the organic solvent I, at certain temperature I carboxylic-amine reaction occuring generates the PAA-DDA graft polymers, this polymer, NIPA NIPAM and cross-linking agent II are dissolved in the organic solvent II, at certain temperature II polymerization reaction take place, generate PNIPAM-PAA-DDA triblock copolymer PNAD;
(4) lecithin, cholesterol, PNAD are dissolved in the mixed liquor of chloroform/methanol with certain mass ratio, evacuation in Rotary Evaporators makes the solvent rear film forming of volatilizing fully, adds deionized water, under magnetic agitation, film is come off, make the liposome suspension;
(5) step (4) gained liposome suspension is put into the autoclave that places water bath with thermostatic control with step (2) gained composite particles aqueous solution, pass into carbon dioxide, under certain temperature and pressure, stir hatching; Hatching is cooled to room temperature after finishing, and slowly carbon dioxide gas namely gets the target liposome solutions.
2. the pH of a kind of interior water carried magnetic carbon quantum dot according to claim 1 and the preparation method of hot Lazer's property liposome, it is characterized in that, iron chloride described in the step (1), ferrous sulfate and thioglycolic acid concentration ratio are 1: 1: 2~5: 1: 6, alkali condition is pH7~8, magnetic nano particle is of a size of 10~30nm, and the addition of polymine is 0.1~0.5% of described homogenizing aqueous solution quality.
3. the pH of a kind of interior water carried magnetic carbon quantum dot according to claim 1 and the preparation method of hot Lazer's property liposome, it is characterized in that, glucose sugar described in the step (2) is 1~5 with the mass volume ratio of Polyethylene Glycol: 5~25g/mL, the microwave power of described microwave reactor is 540W, and the response time is 1~10min.
4. the pH of a kind of interior water carried magnetic carbon quantum dot according to claim 1 and the preparation method of hot Lazer's property liposome, it is characterized in that, PNIPAM, PAA, DDA monomer mole ratio are 94: 1: 5~79: 1: 20 among the PNIPAM-PAA-DDA triblock copolymer PNAD described in the step (3), cross-linking agent I is dicyclohexylcarbodiimide DDC, organic solvent I is N, N '-dimethyl formamide DMF, temperature I is 20~90 ℃, cross-linking agent II is azodiisobutyronitrile AIBN, organic solvent II is 1,4-dioxane, temperature II are 50~80 ℃.
5. the pH of a kind of interior water carried magnetic carbon quantum dot according to claim 1 and the preparation method of hot Lazer's property liposome, it is characterized in that, the mass ratio of lecithin described in the step (4), cholesterol, PNAD is 1: 1: 1~5: 1: 0.1, the volume ratio of chloroform/methanol is 1: 1~3: 1, and the rotary evaporation temperature is 35~45 ℃.
6. the pH of a kind of interior water carried magnetic carbon quantum dot according to claim 1 and the preparation method of hot Lazer's property liposome, it is characterized in that, the mass ratio of the composite particles aqueous solution described in the step (5) and liposome suspension is 1: 5~1: 10, bath temperature is 40~50 ℃, setting pressure is 10~30MPa, and the stirring brooding time is 20~50min.
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CN107384370A (en) * | 2017-07-21 | 2017-11-24 | 浙江理工大学 | A kind of preparation method for the nanoparticle for being embedded with the carbon quantum dot based on sugarcane synthesis |
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