CN106619517A - Preparation method of organic-inorganic network double-reinforced compound liposome - Google Patents
Preparation method of organic-inorganic network double-reinforced compound liposome Download PDFInfo
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- CN106619517A CN106619517A CN201710022774.8A CN201710022774A CN106619517A CN 106619517 A CN106619517 A CN 106619517A CN 201710022774 A CN201710022774 A CN 201710022774A CN 106619517 A CN106619517 A CN 106619517A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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Abstract
The invention discloses a preparation method of organic-inorganic network double-reinforced compound liposome. The method utilizes organic siloxane, containing ultraviolet-polymerizable functional groups, as a silicon source; the method comprises the steps of introducing the silicon source into a hydrophobic lipid bilayer, carrying out in situ hydrolysis-condensation reaction to generate a C=C-containing silica shell, and then promoting the C=C to polymerize by means of ultraviolet irradiation so as to obtain the organic-inorganic network double-reinforced compound liposome. The preparation method is environment-friendly in used raw materials, less in consumption of the organic siloxane, simple in preparation method and mild in reaction conditions; furthermore, the obtained liposome has good stability, and has wide application prospect in the field of biological medicines and especially in the aspect of using the liposome as a drug carrier.
Description
Technical field
The invention belongs to Bio-Nano-Materials technical field, and in particular to a kind of by containing ultraviolet light polymerizable functional group
Organosiloxane is introduced into hydrophobic lipid bilayer, and one-step method prepares liposome/organosilicon composite microcapsule, and is polymerized by ultraviolet radioactive
The method for forming the complex liposome of the dual reinforcing of organic-inorganic network.
Background technology
Liposome is that phospholipid bilayer is dispersed in water the near-spherical to be formed, and has the closing capsule of internal water cavity
Bubble, with good biocompatibility and can carry various hydrophilic and hydrophobic substance.Grind in 20 century 70s, Bangham etc.
The person of studying carefully studies liposome first as drug carrier system, however, liposome extremely unstable itself is susceptible to fusion
Aggregation.This be due to the oxidation and hydrolysis of phosphatide, bilayer merges aggregation increases the permeability of liposome, so as to medicine occur
The phenomenons such as thing leakage.In order to improve the stability of liposome, scientists have respectively miscellaneous by organic and inorganic and organic and inorganic
Change material carries out surface modification to it.For example, Sylvie B é gu seminars (Chem.Commun., 2003,640-641) report
A kind of preparation method of liposome/silica composite microcapsule, i.e., with liposome as soft template, then introduce silicon source
(TEOS), by its sol-gel process, layer of silicon dioxide shell is coated on the template, and be by this material designation
“liposil”；(the Colloids Surf.B such as Cao Zhong:Biointerfaces, 2014,116,327-333) propose one kind newly
Strategy preparing the liposome with high stability, will carbonate network structure be coated on silicon substrate complex liposome and formed
A kind of ceramic mould liposome of hybrid inorganic-organic.In lipid composite made above, two-step reaction is all at least needed, grasped
Make process complexity and the structure of liposome itself is easily destroyed in preparation process.Based on this, inventor be located research group
(ACS Appl.Mater.Interfaces, 2015,7,25039-25044) it is proposed that one kind directly prepared with one-step method it is compound
The system of lipid microcapsule, i.e., using the hydrophobic property inside phospholipid bilayer, during liposome is prepared, will be oil loving
TEOS confinements are encapsulated in lipid bilayer the condensation that is hydrolyzed, and in-situ deposition forms silica shell, so as to prepare fat
Plastid/silica composite microcapsule.But the lipid composite microcapsule room temperature for preparing of the method is melted completely after placing 5～6 days
Aggregation is closed, stability still has much room for improvement.
The content of the invention
The technical problem to be solved is that a kind of simple to operate, reaction condition of offer is gentle and stability is more preferable
The dual reinforcing of organic and inorganic network complex liposome preparation method.
The technical scheme that solution above-mentioned technical problem is adopted is made up of following step：
1st, liposome/organosilicon composite microcapsule is prepared
In mass ratio it is 1 by cholesterol, phosphatide, organosiloxane:4:0.8～1.2 adds in chloroform, and mixing is equal
It is even, chloroform is removed in 35～45 DEG C of rotary evaporations, the PBS that 0.01mol/L pH value is 7 is added, courage is solid
Alcohol is 1mg with the quality-volume ratio of phosphate buffer:0.3～0.5mL, 35～45 DEG C of aquations are simultaneously ultrasonic 30～45 minutes, obtain
The liposome of organosiloxane is encapsulated in lipid bilayer；Adjusted with the ammoniacal liquor that pH value is 10 and encapsulate in lipid bilayer organosiloxane
The pH value of liposome is stirred at room temperature reaction 6～8 days to 8～9, obtains liposome/organosilicon composite microcapsule.
2nd, the complex liposome of the dual reinforcing of organic and inorganic network is prepared
By the liposome for obtaining/organosilicon composite microcapsule centrifugation, the gained precipitation phosphorus that 0.01mol/L pH value is 7
Phthalate buffer washs colourless to supernatant, adds light trigger, is uniformly dispersed, and using ultraviolet radiation, obtains final product organic and inorganic
The complex liposome of the dual reinforcing of network.
Above-mentioned organosiloxane is 3- propyl methacrylate trimethicones；Described light trigger is 2,4,6- tri-
Methyl benzoyl-diphenyl phosphine oxide；Described phosphatide is egg yolk lecithin or soybean lecithin.
In above-mentioned steps 2, preferred organosiloxane is 1 with the mass ratio of light trigger:0.005～0.02.
In above-mentioned steps 2, further preferably adopt wavelength for 365nm ultraviolet light irradiation 5～30 minutes.
The invention has the advantages that：
1st, the present invention adopts phosphatide, cholesterol, organosiloxane for raw material, and the hydrophobic direct step of organosiloxane is drawn
Enter in hydrophobic lipid bilayer, hydrolysis-condensation reaction generation silica shell, and titanium dioxide occur by the way that organosiloxane is in situ
Silicon shell contains ultraviolet polymerisable functional group C=C, and C=C is polymerized under ultraviolet irradiation, and the organic-inorganic network of formation is dual to be added
Solid complex liposome.
2nd, raw materials used environmental protection of the invention, preparation method is simple, and reaction condition is gentle, workable, double from fat
Organosiloxane is introduced in layer, the amount of required organosiloxane is less.
3rd, micro-capsule remains to keep good pattern after present invention gained liposome room temperature is placed 22 days, stablizes with good
Property, the fields such as the long-term preservation of medicine are can be applicable to, and polytype is prepared to the later stage for the present invention and functional characteristic is combined
Liposome provides thinking.
Description of the drawings
Fig. 1 is the scanning electron microscope (SEM) photograph of liposome/organosilicon composite microcapsule prepared by embodiment 1.
Fig. 2 is the scanning electron microscope (SEM) photograph of the complex liposome of the dual reinforcing of organic and inorganic network prepared by embodiment 1.
Fig. 3 is the energy dispersion X-ray spectrogram of liposome/organosilicon composite microcapsule prepared by embodiment 1.
Fig. 4 is that embodiment 1 prepares liposome/organosilicon composite microcapsule (curve 1) and the dual reinforcing of organic and inorganic network
The infrared spectrogram of complex liposome (curve 2).
Fig. 5 is sweeping after the complex liposome room temperature of the dual reinforcing of organic and inorganic network prepared by embodiment 1 is placed 22 days
Retouch electron microscope.
Fig. 6 is the scanning electron microscope (SEM) photograph of liposome/organosilicon composite microcapsule prepared by embodiment 2.
Fig. 7 is the scanning electron microscope (SEM) photograph of liposome/organosilicon composite microcapsule prepared by embodiment 3.
Fig. 8 is the scanning electron microscope (SEM) photograph of the complex liposome of the dual reinforcing of organic and inorganic network prepared by embodiment 4.
Fig. 9 is the scanning electron microscope (SEM) photograph of the complex liposome of the dual reinforcing of organic and inorganic network prepared by embodiment 5.
Specific embodiment
With reference to the accompanying drawings and examples the present invention is described in more detail, but protection scope of the present invention is not limited only to
These embodiments.
Embodiment 1
1st, liposome/organosilicon composite microcapsule is prepared
25mg cholesterol, 100mg egg yolk lecithins, 25mg 3- propyl methacrylates trimethicone are added
In 10mL chloroforms, room temperature ultrasonic mixing is uniform, and in 40 DEG C of rotary evaporations chloroforms are removed, and obtains one layer of homogeneous transparent
Film, is subsequently adding the PBS that 10mL 0.01mol/L pH value is 7,40 DEG C of aquations 30 minutes, then 35～40
Ultrasound 40 minutes at DEG C, supersonic frequency is 100Hz, power is 100W, obtains encapsulating 3- propyl methacrylates three in lipid bilayer
The liposome of methylsiloxane, is adjusted with the ammoniacal liquor that pH value is 10 and encapsulate in lipid bilayer 3- propyl methacrylate trimethyl silica
The pH value of the liposome of alkane is stirred at room temperature reaction 7 days to 8～9, obtains liposome/organosilicon composite microcapsule.
2nd, the complex liposome of the dual reinforcing of organic and inorganic network is prepared
The liposome for obtaining/organosilicon composite microcapsule is separated with 4000 revs/min of centrifugation, the precipitation for obtaining is used
It is colourless to supernatant that 0.01mol/L pH value is that 7 PBS is washed, and adds the trimethylbenzene first of 0.25mg 2,4,6-
Acyl group-diphenyl phosphine oxide, stirs, adopt wavelength for 365nm ultraviolet light irradiation 15 minutes, obtain organic and inorganic net
The complex liposome of the dual reinforcing of network.
Using ESEM, energy dispersion X-ray spectrum and infrared spectrometer respectively to liposome obtained above/organic
Silicon composite microcapsule, the complex liposome of the dual reinforcing of organic and inorganic network are characterized, as a result such as Fig. 1～4.Can by Fig. 1 and 2
See, after ultraviolet irradiation polymerization, pattern is in still club shaped structure to liposome/organosilicon composite microcapsule, and size does not have significant change.Root
According to Fig. 3 know prepared liposome/organosilicon composite microcapsule really contain Si elements, although intensity be not it is very high, this be due to
During preparing sample, the amount for introducing organic silicon source is just especially few, but can illustrate silica with reference to scanning electron microscopic picture
Shell has been formed.From fig. 4, it can be seen that compared to liposome/organosilicon composite microcapsule (curve 1), organic and inorganic network is dual to be added
Solid complex liposome (curve 2) in 1648cm-1The stretching vibration absworption peak intensity of place's correspondence C=C double bonds substantially weakens a lot,
Functions group C=C there occurs polymerisation by ultraviolet irradiation, forms one layer of inorganic grid and strengthens lipid again
Body.
After the complex liposome room temperature of the dual reinforcing of organic and inorganic network of above-mentioned preparation is placed 22 days, using scanning
Electronic Speculum is characterized, and as a result sees Fig. 5.As seen from the figure, complex liposome pattern still keeps good after room temperature is placed 22 days, illustrates it
With good stability.
Embodiment 2
Preparing in liposome/organosilicon composite microcapsule step 1 in embodiment 1, by 3- propyl methacrylate trimethyls
The consumption of siloxanes increases to 30mg, and other steps of the step are same as Example 1, obtain liposome/organosilicon be combined it is micro-
Capsule (see Fig. 6).The step of the present embodiment prepares the complex liposome of organic and inorganic network dual reinforcing 2 is same as Example 1.
Embodiment 3
Preparing in liposome/organosilicon composite microcapsule step 1 in embodiment 1, by 3- propyl methacrylate trimethyls
The consumption of siloxanes is reduced to 20mg, and other steps of the step are same as Example 1, obtain liposome/organosilicon be combined it is micro-
Capsule (see Fig. 7).The step of the present embodiment prepares the complex liposome of organic and inorganic network dual reinforcing 2 is same as Example 1.
Embodiment 4
The step of the present embodiment prepares liposome/organosilicon composite microcapsule is same as Example 1.Preparing organic and inorganic
In the complex liposome step 2 of the dual reinforcing of network, adopt wavelength for 365nm ultraviolet light irradiation 5 minutes, the step other
Step is same as Example 1, obtains the complex liposome (see Fig. 8) of the dual reinforcing of organic and inorganic network.
Embodiment 5
The step of the present embodiment prepares liposome/organosilicon composite microcapsule is same as Example 1.Preparing organic and inorganic
In the complex liposome step 2 of the dual reinforcing of network, adopt wavelength for 365nm ultraviolet light irradiation 30 minutes, the step its
His step is same as Example 1, obtains the complex liposome (see Fig. 9) of the dual reinforcing of organic and inorganic network.
Claims (4)
1. the preparation method of the complex liposome of the dual reinforcing of a kind of organic and inorganic network, it is characterised in that it is by following step
Composition：
(1) liposome/organosilicon composite microcapsule is prepared
In mass ratio it is 1 by cholesterol, phosphatide, organosiloxane:4:0.8～1.2 adds in chloroform, is well mixed,
35～45 DEG C of rotary evaporations remove chloroform, add the PBS that 0.01mol/LpH values are 7, cholesterol and phosphorus
Quality-the volume ratio of phthalate buffer is 1mg:0.3～0.5mL, 35～45 DEG C of aquations are simultaneously ultrasonic 30～45 minutes, obtain fat double
The liposome of organosiloxane is encapsulated in layer；The liposome that organosiloxane is encapsulated in lipid bilayer is adjusted with the ammoniacal liquor that pH value is 10
PH value to 8～9, reaction is stirred at room temperature 6～8 days, obtain liposome/organosilicon composite microcapsule；
(2) complex liposome of the dual reinforcing of organic and inorganic network is prepared
By the liposome for obtaining/organosilicon composite microcapsule centrifugation, the gained precipitation phosphate that 0.01mol/L pH value is 7
Buffer solution to supernatant is colourless, adds light trigger, is uniformly dispersed, and using ultraviolet radiation, obtains final product organic and inorganic network
The complex liposome of dual reinforcing；
Above-mentioned organosiloxane is 3- propyl methacrylate trimethicones；Described light trigger is 2,4,6- trimethyls
Benzoyl-diphenyl phosphine oxide.
2. the preparation method of the complex liposome of the dual reinforcing of organic and inorganic network according to claim 1, its feature exists
In：In step (1), described phosphatide is egg yolk lecithin or soybean lecithin.
3. the preparation method of the complex liposome of the dual reinforcing of organic and inorganic network according to claim 1, its feature exists
In：In step (2), the organosiloxane is 1 with the mass ratio of light trigger:0.005～0.02.
4. the preparation method of the complex liposome of the dual reinforcing of organic and inorganic network according to claim 1, its feature exists
In：In step (2), adopt wavelength for 365nm ultraviolet light irradiation 5～30 minutes.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1127909A1 (en) * | 2000-02-24 | 2001-08-29 | Société de Technologie Michelin | Composition of curable rubber, suitable to produce a tire and tire containing this composition |
| CN103881005A (en) * | 2014-03-18 | 2014-06-25 | 陕西师范大学 | Light-curing preparation method of rare earth bonded fluorescent gel glass |
| CN104146987A (en) * | 2014-07-28 | 2014-11-19 | 陕西师范大学 | Simple preparation method of lipidosome/silicon dioxide composite nanocapsules |
| CN105037662A (en) * | 2015-06-30 | 2015-11-11 | 陕西师范大学 | Preparation method of europium-bonded fluorescent nano silica microsphere through light curing |
-
2017
- 2017-01-12 CN CN201710022774.8A patent/CN106619517B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1127909A1 (en) * | 2000-02-24 | 2001-08-29 | Société de Technologie Michelin | Composition of curable rubber, suitable to produce a tire and tire containing this composition |
| CN103881005A (en) * | 2014-03-18 | 2014-06-25 | 陕西师范大学 | Light-curing preparation method of rare earth bonded fluorescent gel glass |
| CN104146987A (en) * | 2014-07-28 | 2014-11-19 | 陕西师范大学 | Simple preparation method of lipidosome/silicon dioxide composite nanocapsules |
| CN105037662A (en) * | 2015-06-30 | 2015-11-11 | 陕西师范大学 | Preparation method of europium-bonded fluorescent nano silica microsphere through light curing |
Non-Patent Citations (1)
| Title |
|---|
| QI JING-JING ET AL.: ""Encapsulation and release of doxorubicin from silica-coated liposome"", 《JOURNAL OF CLINICAL REHABILITATIVE TISSUE ENGINEERING RESEARCH》 * |
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