CN101564380A - Magnetic liposome and method for preparing same - Google Patents
Magnetic liposome and method for preparing same Download PDFInfo
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- CN101564380A CN101564380A CNA2009100227175A CN200910022717A CN101564380A CN 101564380 A CN101564380 A CN 101564380A CN A2009100227175 A CNA2009100227175 A CN A2009100227175A CN 200910022717 A CN200910022717 A CN 200910022717A CN 101564380 A CN101564380 A CN 101564380A
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Abstract
The invention discloses a magnetic liposome and a method for preparing the same. The magnetic liposome wraps medicine inside the liposome; and magnetic particles are coated outside the liposome. The preparation method comprises the following steps that: a yolk lecithin solution and a cholesterin solution are mixed in an eggplant-shaped bottle according to the molar ratio of 2:1 to 2.5:1; the mixture is subjected to rotary evaporation to form a liposome film; then a phosphate buffering solution is used to carry out full hydration on the liposome film to obtain the liposome of which the surface is provided with negative charges; then, cationic polyelectrolyte-poly diallyl dimethyl ammonium chloride, anionic polyelectrolyte which is sodium polystyrene sulfonate and cationic polyelectrolyte which is poly diallyl dimethyl ammonium chloride are subjected to alternate adsorption; and finally, through the charge action and a self-assembling method, Fe3O4 magnetic particles of which the surfaces are provided with negative charges are deposited on the surface of the liposome to obtain the magnetic liposome. As the inside of the liposome is packed with the medicine, the magnetic particles are deposited on the surface of the liposome and a finite space of the inner space of the liposome is totally packed with the medicine, the packing amount of the medicine is improved and the magnetic content is simultaneously improved.
Description
Technical field
The present invention relates to a kind of liposome, particularly magnetic liposome.The preparation method that also relates to magnetic liposome.
Background technology
The Chinese invention patent of document 1 " publication number is CN100998563 " discloses a kind of preparation method of drug loaded magnetic liposome, at first the doxorubicin medicine dissolution is formed doxorubicin magnetic liquid in the magnetic liquid for preparing, with L-α-PHOSPHATIDYL ETHANOLAMINE, cholesterol, L-α-phosphatidylcholine makes liposome membrane by 7: 2: 1 weight ratio, again doxorubicin magnetic liquid is added in the eggplant-shape bottle that forms liposome membrane, at room temperature carrying out vortex vibration 30min comes off fully until thin film, first liquid poured in vitro carry out Ultrasonic Pulverization discontinuous pulses 20min, leave standstill and formed magnetic pegylated liposomal doxorubicin in 12 hours.
The Chinese invention patent of document 2 " publication number is CN1559439 " discloses a kind of preparation method of drug loaded magnetic liposome, at first adopt thin film rotary evaporator to form a uniform liposome membrane at the eggplant-shape bottle inwall, the suspension of preparation arsenicum and manganese-zinc ferrite magnetic nano particle, this suspension is added in the above-mentioned eggplant-shape bottle that contains thin film, 40 ± 5 ℃ of isothermal vibration to thin film come off, and multigelation and supersound process make nanometer arsenicum magnetic liposome for 3 times.
The disclosed magnetic lipid body structure of above document as shown in Figure 2, liposome 3 together is wrapped in its inside with magnetic particle 2 and medicine 1, there are some limitation in this structure.The first, magnetic content is not high, magnetic responsiveness is low.Because the inner space of the phospholipid bilayer of liposome, particularly small unilamellar vesicle (SUV) is limited, causes only having more a spot of magnetic particle can wrap in liposome interior; And magnetic particle density is big, free settling, when the liposome hydration forms vesicle, is difficult to evenly coat wherein.The second, the bag carrying capacity of medicine is low.Because the liposome interior space is limited, when magnetic particle occupies wherein, cause the bag carrying capacity of medicine to descend.
Summary of the invention
The low deficiency of bag carrying capacity of, medicine low for the liposome magnetic content that overcomes art methods preparation, the invention provides a kind of magnetic liposome, bag medicine carrying thing in the liposome, magnetic particle is deposited on surface of liposome, can in the bag carrying capacity that improves medicine, improve magnetic content.The present invention also provides the preparation method of this magnetic liposome.
The technical solution adopted for the present invention to solve the technical problems: a kind of magnetic liposome, comprise medicine, liposome and magnetic particle, be characterized in that described liposome interior is a medicine, surface of liposome is a magnetic particle.
A kind of preparation method of above-mentioned magnetic liposome is characterized in comprising the steps:
(a) respectively Ovum Gallus domesticus Flavus lecithin, cholesterol are dissolved in volume ratio methanol: in chloroform=1: 2 mixed solvent, obtain the Ovum Gallus domesticus Flavus lecithin solution of 0.1g/mL and the cholesterol solution of 0.1g/mL respectively, Ovum Gallus domesticus Flavus lecithin solution and cholesterol solution are mixed with 2: 1～2.5: 1 mol ratio in eggplant-shape bottle, and rotary evaporation forms liposome membrane;
(b) be that 7.4 phosphate buffered solution joins in the eggplant-shape bottle that forms liposome membrane with pH, the cumulative volume of Ovum Gallus domesticus Flavus lecithin solution and cholesterol solution and the volume ratio of phosphate buffered solution are 1: 4～1: 10, use vortex mixer to revolve and mix 20～40min, use the high speed dispersion homogenizer to disperse 5～10min, fully hydration centrifugal washing later on is 2～3 times, obtains the liposome that the surface has negative electricity;
(c) surface that step (b) is obtained has electronegative liposome and is dispersed in the diallyl dimethyl ammoniumchloride aqueous solution that concentration is 0.8～1.2mg/ (ml 0.5M NaCl), the mass ratio of liposome and diallyl dimethyl ammoniumchloride aqueous solution is 1: 60～1: 100, centrifugal washing behind standing adsorption 20～40min;
(d) liposome that step (c) is obtained is dispersed in the kayexalate aqueous solution that concentration is 0.3～0.6mg/ (ml 0.5M NaCl), the mass ratio of liposome and kayexalate aqueous solution is 1: 60～1: 100, centrifugal washing behind standing adsorption 20～40min;
(e) liposome that step (d) is obtained is dispersed in the diallyl dimethyl ammoniumchloride aqueous solution that concentration is 0.8～1.2mg/ (ml 0.5M NaCl), the mass ratio of liposome and diallyl dimethyl ammoniumchloride aqueous solution is 1: 60～1: 100, centrifugal washing behind standing adsorption 20～40min;
(f) with mass percentage concentration 2%, have the Fe of negative electricity
3O
4Nanoparticle magnetic fluid thin liquid slowly adds in the liposome that step (e) obtains, and the mass ratio of liposome and magnetic fluid thin liquid is 1: 0.8～1: 2.5, separates behind standing adsorption 20～40min, obtains magnetic liposome.
The invention has the beneficial effects as follows: because bag medicine carrying thing in the liposome, magnetic particle is deposited on surface of liposome, and the spatial confined space of liposome interior is all wrapped the medicine carrying thing, has improved the bag carrying capacity of medicine, has improved magnetic content simultaneously.
Below in conjunction with drawings and Examples the present invention is elaborated.
Description of drawings
Fig. 1 is the structural representation of magnetic liposome of the present invention.
Fig. 2 is the structural representation of prior art magnetic liposome.
Fig. 3 is the TEM photo of magnetic liposome of the present invention.
The specific embodiment
With reference to Fig. 1, Fig. 3, the structure of magnetic liposome of the present invention is, liposome 3 inside are medicines 1, and liposome 3 surfaces are magnetic particles 2.Can be clear that the medicine of liposome interior and the magnetic particle on surface from the TEM photo of magnetic liposome.
Embodiment 1: respectively Ovum Gallus domesticus Flavus lecithin, cholesterol were dissolved in methanol-chloroform mixed organic solvents (1: 2, v/v) in, obtain the Ovum Gallus domesticus Flavus lecithin solution of 0.1g/mL and the cholesterol solution of 0.1g/mL, 10mL Ovum Gallus domesticus Flavus lecithin solution and 2.5mL cholesterol solution are mixed in eggplant-shape bottle, and rotary evaporation forms liposome membrane.50mL phosphate buffered solution (pH, 7.4) is added in the eggplant-shape bottle that forms liposome membrane, and the use vortex mixer revolves and mixes 20min, uses the high speed dispersion homogenizer to disperse 5min, and fully hydration centrifugal washing later on is 2 times, obtains the liposome that the surface has negative electricity.The liposome 1g that above-mentioned surface is had negative electricity is dispersed in the diallyl dimethyl ammoniumchloride aqueous solution that 60mL concentration is 0.8mg/ (ml 0.5M NaCl) centrifugal washing behind the standing adsorption 20min; Redispersion is in the kayexalate aqueous solution of 0.5mg/ (ml 0.5M NaCl) in 60mL concentration, centrifugal washing behind the standing adsorption 20min; Redispersion is in the diallyl dimethyl ammoniumchloride aqueous solution of 0.8mg/ (ml 0.5M NaCl) in 60mL concentration, centrifugal washing behind the standing adsorption 20min.With 1g concentration is that 2% magnetic fluid thin liquid slowly adds in the above-mentioned liposome, separates behind the standing adsorption 20min, obtains magnetic liposome.
Embodiment 2: respectively Ovum Gallus domesticus Flavus lecithin, cholesterol were dissolved in methanol-chloroform mixed organic solvents (1: 2, v/v) in, obtain the Ovum Gallus domesticus Flavus lecithin solution of 0.1g/mL and the cholesterol solution of 0.1g/mL, 10mL Ovum Gallus domesticus Flavus lecithin solution and 2mL cholesterol solution are mixed in eggplant-shape bottle, and rotary evaporation forms liposome membrane.60mL phosphate buffered solution (pH, 7.4) is added in the eggplant-shape bottle that forms liposome membrane, and the use vortex mixer revolves and mixes 30min, uses the high speed dispersion homogenizer to disperse 6min, and fully hydration centrifugal washing later on is 3 times, obtains the liposome that the surface has negative electricity.The liposome 1g that above-mentioned surface is had negative electricity is dispersed in the diallyl dimethyl ammoniumchloride aqueous solution that 70mL concentration is 1mg/ (ml 0.5M NaCl) centrifugal washing behind the standing adsorption 20min; Redispersion is in the kayexalate aqueous solution of 0.4mg/ (ml 0.5M NaCl) in 70mL concentration, centrifugal washing behind the standing adsorption 20min; Redispersion is in the diallyl dimethyl ammoniumchloride aqueous solution of 1mg/ (ml 0.5M NaCl) in 70mL concentration, centrifugal washing behind the standing adsorption 20min.With 1.5g concentration is that 2% magnetic fluid thin liquid slowly adds in the above-mentioned liposome, separates behind the standing adsorption 20min, obtains magnetic liposome.
Embodiment 3: respectively Ovum Gallus domesticus Flavus lecithin, cholesterol were dissolved in methanol-chloroform mixed organic solvents (1: 2, v/v) in, obtain the Ovum Gallus domesticus Flavus lecithin solution of 0.1g/mL and the cholesterol solution of 0.1g/mL, 10mL Ovum Gallus domesticus Flavus lecithin solution and 2mL cholesterol solution are mixed in eggplant-shape bottle, and rotary evaporation forms liposome membrane.70mL phosphate buffered solution (pH, 7.4) is added in the eggplant-shape bottle that forms liposome membrane, and the use vortex mixer revolves and mixes 30min, uses the high speed dispersion homogenizer to disperse 8min, and fully hydration centrifugal washing later on is 2 times, obtains the liposome that the surface has negative electricity.The liposome 1g that above-mentioned surface is had negative electricity is dispersed in the diallyl dimethyl ammoniumchloride aqueous solution that 70mL concentration is 1.2mg/ (ml 0.5M NaCl) centrifugal washing behind the standing adsorption 30min; Redispersion is in the kayexalate aqueous solution of 0.5mg/ (ml 0.5M NaCl) in 70mL concentration, centrifugal washing behind the standing adsorption 30min; Redispersion is in the diallyl dimethyl ammoniumchloride aqueous solution of 1.2mg/ (ml 0.5M NaCl) in 70mL concentration, centrifugal washing behind the standing adsorption 30min.With 1.8g concentration is that 2% magnetic fluid thin liquid slowly adds in the above-mentioned liposome, separates behind the standing adsorption 30min, obtains magnetic liposome.
Embodiment 4: respectively Ovum Gallus domesticus Flavus lecithin, cholesterol were dissolved in methanol-chloroform mixed organic solvents (1: 2, v/v) in, obtain the Ovum Gallus domesticus Flavus lecithin solution of 0.1g/mL and the cholesterol solution of 0.1g/mL, 10mL Ovum Gallus domesticus Flavus lecithin solution and 2.5mL cholesterol solution are mixed in eggplant-shape bottle, and rotary evaporation forms liposome membrane.With 60mL phosphate buffered solution (pH, 7.4) add in the eggplant-shape bottle that forms liposome membrane, use vortex mixer to revolve and mix 40min, use the high speed dispersion homogenizer to disperse 10min, fully hydration centrifugal washing later on is 3 times, obtains the liposome that the surface has negative electricity.The liposome 1g that above-mentioned surface is had negative electricity is dispersed in the diallyl dimethyl ammoniumchloride aqueous solution that 80mL concentration is 1.2mg/ (ml 0.5M NaCl) centrifugal washing behind the standing adsorption 40min; Redispersion is in the kayexalate aqueous solution of 0.6mg/ (ml 0.5M NaCl) in 80mL concentration, centrifugal washing behind the standing adsorption 40min; Redispersion is in the diallyl dimethyl ammoniumchloride aqueous solution of 1.2mg/ (ml 0.5M NaCl) in 80mL concentration, centrifugal washing behind the standing adsorption 40min.With 2.5g concentration is that 2% magnetic fluid thin liquid slowly adds in the above-mentioned liposome, separates behind the standing adsorption 40min, obtains magnetic liposome.
In the process of preparation magnetic liposome, the related various proportions of said method, concentration range, time range have been carried out repeatedly trial-production, all obtained good effect.
Claims (2)
1, a kind of magnetic liposome comprises medicine, liposome and magnetic particle, it is characterized in that: described liposome interior is a medicine, and surface of liposome is a magnetic particle.
2, the preparation method of the described magnetic liposome of a kind of claim 1 is characterized in that comprising the steps:
(a) respectively Ovum Gallus domesticus Flavus lecithin, cholesterol are dissolved in volume ratio methanol: in chloroform=1: 2 mixed solvent, obtain the Ovum Gallus domesticus Flavus lecithin solution of 0.1g/mL and the cholesterol solution of 0.1g/mL respectively, Ovum Gallus domesticus Flavus lecithin solution and cholesterol solution are mixed with 2: 1～2.5: 1 mol ratio in eggplant-shape bottle, and rotary evaporation forms liposome membrane;
(b) be that 7.4 phosphate buffered solution joins in the eggplant-shape bottle that forms liposome membrane with pH, the cumulative volume of Ovum Gallus domesticus Flavus lecithin solution and cholesterol solution and the volume ratio of phosphate buffered solution are 1: 4～1: 10, use vortex mixer to revolve and mix 20～40min, use the high speed dispersion homogenizer to disperse 5～10min, fully hydration centrifugal washing later on is 2～3 times, obtains the liposome that the surface has negative electricity;
(c) surface that step (b) is obtained has electronegative liposome and is dispersed in the diallyl dimethyl ammoniumchloride aqueous solution that concentration is 0.8～1.2mg/ (ml 0.5M NaCl), the mass ratio of liposome and diallyl dimethyl ammoniumchloride aqueous solution is 1: 60～1: 100, centrifugal washing behind standing adsorption 20～40min;
(d) liposome that step (c) is obtained is dispersed in the kayexalate aqueous solution that concentration is 0.3～0.6mg/ (ml 0.5M NaCl), the mass ratio of liposome and kayexalate aqueous solution is 1: 60～1: 100, centrifugal washing behind standing adsorption 20～40min;
(e) liposome that step (d) is obtained is dispersed in the diallyl dimethyl ammoniumchloride aqueous solution that concentration is 0.8～1.2mg/ (ml 0.5M NaCl), the mass ratio of liposome and diallyl dimethyl ammoniumchloride aqueous solution is 1: 60～1: 100, centrifugal washing behind standing adsorption 20～40min;
(f) with mass percentage concentration 2%, have the Fe of negative electricity
3O
4Nanoparticle magnetic fluid thin liquid slowly adds in the liposome that step (e) obtains, and the mass ratio of liposome and magnetic fluid thin liquid is 1: 0.8～1: 2.5, separates behind standing adsorption 20～40min, obtains magnetic liposome.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102114411A (en) * | 2011-01-18 | 2011-07-06 | 湖南师范大学 | Lecithin magnetic nano-composite and preparation method and application thereof |
| CN110571005A (en) * | 2019-09-27 | 2019-12-13 | 广西科技大学 | Immobilized metal ion-magnetic liposome and preparation method and application thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102114411A (en) * | 2011-01-18 | 2011-07-06 | 湖南师范大学 | Lecithin magnetic nano-composite and preparation method and application thereof |
| CN110571005A (en) * | 2019-09-27 | 2019-12-13 | 广西科技大学 | Immobilized metal ion-magnetic liposome and preparation method and application thereof |
| CN110571005B (en) * | 2019-09-27 | 2021-01-01 | 广西科技大学 | Immobilized metal ion-magnetic liposome and preparation method and application thereof |
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Effective date of registration: 20140813 Address after: 226600, Cambridge Road, Haian Development Zone, Haian County, Jiangsu, Nantong province 2 Patentee after: Nantong Cambridge Olein Co., Ltd. Patentee after: Northwestern Polytechnical University Address before: 710072 Xi'an friendship West Road, Shaanxi, No. 127 Patentee before: Northwestern Polytechnical University Effective date of registration: 20140813 Address after: 226600, Cambridge Road, Haian Development Zone, Haian County, Jiangsu, Nantong province 2 Patentee after: Nantong Cambridge Olein Co., Ltd. Patentee after: Northwestern Polytechnical University Address before: 710072 Xi'an friendship West Road, Shaanxi, No. 127 Patentee before: Northwestern Polytechnical University |
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