CN102920659B - Thermosensitive self-assembled liposome and preparation method thereof - Google Patents
Thermosensitive self-assembled liposome and preparation method thereof Download PDFInfo
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- CN102920659B CN102920659B CN201210454377.5A CN201210454377A CN102920659B CN 102920659 B CN102920659 B CN 102920659B CN 201210454377 A CN201210454377 A CN 201210454377A CN 102920659 B CN102920659 B CN 102920659B
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Abstract
The invention relates to a thermosensitive self-assembled liposome and a preparation method thereof, and the component of the liposome is phosphatidyl choline. The preparation method comprises: (1) enabling the phosphatidyl choline and poly N-isopropyl acrylamide to be dissolved in solvent, mixing and stirring and obtaining electronic injection stock solution, wherein mass ratio of the poly N-isopropyl acrylamide and the phosphatidyl choline is 1-5:10, and massic volume ratio of the poly N-isopropyl acrylamide and organic solvent is 1.0-2-0 grams:10-15 milliliters; and (2) carrying out electrostatic spray to the electronic injection stock solution, dropping high purity water and drying by distillation after vacuum drying, and obtaining the self-assembled liposome. The liposome has actual applications in drug controlled release; and the method is simple and rapid, the operation is safe, so that the thermosensitive self-assembled liposome and the preparation method thereof are suitable for relatively large-scale generation, and have a good application prospect.
Description
Technical field
The invention belongs to liposome and preparation field thereof, particularly a kind of temperature sensitive self assembly liposome and preparation method thereof.
Background technology
Molecular self-assembling is exactly that molecule and molecule are under equilibrium condition, because being subject to intermolecular non-covalent bonding force, as hydrogen bond, electrostatic interaction, hydrophobic lipotropism, π-π
interact, the spontaneous combination of Van der Waals force, form and have that structure is clear and definite, the process of the molecule aggregate of stable performance.
Self-assembling technique is the more emerging problem in modern scientific research field, and utilizing self assembly to synthesize new material has huge potentiality manufacturing on the controlled new material of high-quality, domain character.Self-assembled material is one of most important field of 21 century Materials Science and Engineering, and self-assembling technique, as the emerging processing and manufacturing technology of a class, has broad application prospects.
Phosphatidylcholine is a kind of amphiphatic molecule, hydrophilic head and hydrophobic afterbody, consists of.Phosphatidylcholine is the main component of phospholipid, is also the important component of function of human body, and phosphatidyl choline transmits the instruction of brain rapidly, and information transmission speed is faster, and memory is stronger; There is emulsification function simultaneously, unnecessary fat can be turned to less emulsion droplet and excrete.Therefore utilize the compatibility of phosphatidylcholine and organism and amphipathic, be widely used in recent years the preparation of pharmaceutical carrier and self-assembling nanoparticles.Phosphatidylcholine first can not form self assembly liposome in normal condition, only in relative external environment, just can excite self-assembling function.
Poly-N-isopropyl acrylamide is a kind of typical temperature sensitivity macromolecule, current research shows that poly-N-isopropyl acrylamide chain has an obvious phase change near 32 ℃, 32 ℃ of following polymer chains exist with the random coil form stretching, higher than 32 ℃ of polymer chains, can be curled into the bead of collapsing, this temperature is called as minimum critical solution temperature (LCST).
Electrostatic spray obtains people's extensive concern in recent years as a kind of new method of preparing microsphere, utilize the Macromolecule Prodrug microsphere that electrostatic spray method makes aspect medicament slow release, to have good therapeutic effect.The cardinal principle of electrostatic spray be macromolecular solution under the pushing of syringe pump, thereby enter into high voltage electric field, be split into many tiny droplets, thereby droplet solvent evaporation in course of injection forms needed microsphere.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of temperature sensitive self assembly liposome and preparation method thereof, and self assembly liposome prepared by the method is having practical application aspect the medicine controlled releasing in later stage; The inventive method is simple, quick, handling safety is applicable to fairly large generation, has a good application prospect.
A kind of temperature sensitive self assembly liposome of the present invention, the component of described liposome is phosphatidylcholine.
The preparation method of a kind of temperature sensitive self assembly liposome of the present invention, comprising:
(1) phosphatidylcholine, poly-N-isopropyl acrylamide are dissolved in solvent, mix, stir, obtain EFI stock solution, wherein the mass ratio of poly-N-isopropyl acrylamide and phosphatidylcholine is 1 ~ 5:10, and the mass volume ratio of poly-N-isopropyl acrylamide and organic solvent is 1.0 ~ 2.0g:10 ~ 15mL;
(2) above-mentioned EFI stock solution is carried out to electrostatic spray, drip high purity water after vacuum drying, evaporate to dryness, obtains self assembly liposome.
In described step (1), solvent is chloroform and/or dehydrated alcohol.
In described step (2), the technological parameter of electrostatic spray is: flow velocity 0.5-1.2mL/h, and dash receiver is 10-25cm from the distance of EFI mouth, and voltage is 8-18kv, and ambient temperature is 15-25 ℃, and ambient humidity is 45-80%.
In described step (2), electrostatic spray number of times is 3 ~ 4 times.
The volume that drips high purity water in described step (2) is 2-10mL.
In described step (2), evaporate to dryness temperature is 4 ~ 45 ℃.
Gained liposome of the present invention is, in the temperature environment higher than 32 ℃, self assembly occurs, and forms self assembly liposome.
beneficial effect
(1) the self assembly liposome that prepared by the present invention is having practical application aspect the medicine controlled releasing in later stage;
(2) simple, quick, the handling safety of the inventive method is applicable to fairly large production, has a good application prospect.
Accompanying drawing explanation
Fig. 1 is the stereoscan photograph of EFI PNIPAm/PC microsphere in embodiment 1;
Fig. 2 is the temperature sensitive self assembly liposome of the embodiment 2 gained stereoscan photograph at 24 ℃;
Fig. 3 is the temperature sensitive self assembly liposome of the embodiment 3 gained stereoscan photograph at 45 ℃.
The specific embodiment
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.In addition should be understood that those skilled in the art can make various changes or modifications the present invention after having read the content of the present invention's instruction, these equivalent form of values fall within the application's appended claims limited range equally.
Embodiment 1
Take the phosphatidylcholine of 0.05g, be dissolved in 5ml chloroform, add 0.5g poly-N-isopropyl acrylamide, on magnetic stirring apparatus, at room temperature stir, obtain temperature sensitive polymer EFI stock solution.
The EFI stock solution preparing is imported in administrator (5mL syringe), adopt No. 9 injection needles as playpipe, connect the positive pole of high voltage power supply, aluminium foil microsphere receiver sheet connects negative pole.Electrostatic spray process conditions are: voltage 8kv, and flow velocity 1.0mL/h, dash receiver is apart from 20cm, 25 ℃ of temperature, air humidity 45%.Both obtained temperature sensitive polymer microsphere.The observation figure of this polymer microballoon under Electronic Speculum as shown in Figure 1.
Embodiment 2
Take the phosphatidylcholine of 0.1g, be dissolved in ethanol and the chloroform (ethanol: chloroform=1:1), add 0.5g poly-N-isopropyl acrylamide, at room temperature stir, obtain temperature sensitive polymer EFI stock solution of 5ml on magnetic stirring apparatus.
The EFI stock solution preparing is imported in administrator (5ml syringe), adopt No. 9 injection needles as playpipe, connect the positive pole of high voltage power supply, aluminium foil microsphere receiver sheet connects negative pole.Electrostatic spray process conditions are: voltage 16kv, and flow velocity 1.0mL/h, dash receiver is apart from 25cm, 15 ℃ of temperature, air humidity 80%.Both obtained temperature sensitive polymer microsphere.After vacuum drying, drip high purity water 2ml, natural evaporate to dryness at 24 ℃, with scanning electron microscopic observation, result is as shown in Figure 2.
Embodiment 3
Take the ketoprofen polyvinyl ester of 0.2g, be dissolved in 10ml ethanol and chloroform (ethanol: chloroform=6:4), add 1g poly-N-isopropyl acrylamide, at room temperature stir, obtain temperature sensitive polymer EFI stock solution on magnetic stirring apparatus.
The EFI stock solution preparing is imported in administrator (5ml syringe), adopt No. 9 injection needles as playpipe, connect the positive pole of high voltage power supply, aluminium foil microsphere receiver sheet connects negative pole.Electrostatic spray process conditions are: voltage 18kv, and flow velocity 0.5mL/h, dash receiver is apart from 10cm, 20 ℃ of temperature, air humidity 57%.Both obtained temperature sensitive polymer microsphere.After vacuum drying, drip high purity water 10ml, 45 ℃ of natural evaporates to dryness, with scanning electron microscopic observation, result is as shown in Figure 3.
Claims (5)
1. a preparation method for temperature sensitive self assembly liposome, comprising:
(1) phosphatidylcholine, poly-N-isopropyl acrylamide are dissolved in organic solvent, mix, stir, obtain EFI stock solution, wherein the mass ratio of poly-N-isopropyl acrylamide and phosphatidylcholine is 1～5:10, and the mass volume ratio of poly-N-isopropyl acrylamide and organic solvent is 1.0～2.0g:10～15mL; Wherein organic solvent is chloroform and/or dehydrated alcohol;
(2) above-mentioned EFI stock solution is carried out to electrostatic spray, drip high purity water after vacuum drying, evaporate to dryness, obtains self assembly liposome.
2. the preparation method of a kind of temperature sensitive self assembly liposome according to claim 1, it is characterized in that: in described step (2), the technological parameter of electrostatic spray is: flow velocity 0.5-1.2mL/h, dash receiver is 10-25cm from the distance of EFI mouth, voltage is 8-18kv, ambient temperature is 15-25 ℃, and ambient humidity is 45-80%.
3. the preparation method of a kind of temperature sensitive self assembly liposome according to claim 1, is characterized in that: in described step (2), electrostatic spray number of times is 3～4 times.
4. the preparation method of a kind of temperature sensitive self assembly liposome according to claim 1, is characterized in that: the volume that drips high purity water in described step (2) is 2-10mL.
5. the preparation method of a kind of temperature sensitive self assembly liposome according to claim 1, is characterized in that: in described step (2), evaporate to dryness temperature is 4～45 ℃.
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| CN103211765A (en) * | 2013-05-09 | 2013-07-24 | 东华大学 | Preparation method of medicine-carrying temperature-sensitive self-assembly lipidosome |
| CN109864968A (en) * | 2019-03-14 | 2019-06-11 | 陕西师范大学 | A kind of amido organosilicon liposome/temperature-sensitive hydrogel composite material for encapsulating water soluble drug |
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| DE10242367A1 (en) * | 2002-09-12 | 2004-03-18 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Thermolabile liposomes with good stability in serum, e.g. for release of drugs or contrast agents in hyperthermic areas around tumors, formed from phosphatidyl choline(s) and phosphatidyl oligoglycerol |
| EP2210590A1 (en) * | 2009-01-26 | 2010-07-28 | Academisch Medisch Centrum | Drug delivery system for use in the treatment of vascular and vessel-related pathologies |
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