CN105250238B - Carry polyethylene glycol-ceramide micella and the preparation method and application thereof of salinomycin - Google Patents
Carry polyethylene glycol-ceramide micella and the preparation method and application thereof of salinomycin Download PDFInfo
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- CN105250238B CN105250238B CN201510725278.XA CN201510725278A CN105250238B CN 105250238 B CN105250238 B CN 105250238B CN 201510725278 A CN201510725278 A CN 201510725278A CN 105250238 B CN105250238 B CN 105250238B
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Abstract
The present invention relates to pharmaceutical technology field, specifically a kind of polyethylene glycol ceramide micella for carrying salinomycin, which is：Using polyethylene glycol ceramide as carrier, the micella of salinomycin is contained.The present invention also provides the preparation methods of the micella, and are preparing the application in treating liver-cancer medicine.The novel load salinomycin polyethylene glycol ceramide micella of the present invention can improve chemotherapeutics salinomycin curative effect, it can reach the effect of liver cancer targeting stem cell and liver cancer cells while reducing poisonous side effect of medicine, this is a kind of new strategy of liver cancer treatment, utilize the advantage of small particle micellar carrier, Nano medication targeting therapy on tumor is prepared, is had broad application prospects.
Description
Technical field
The present invention relates to pharmaceutical technology fields, specifically, being a kind of polyethylene glycol-nerve of new preparation load salinomycin
The method of amide micella, it can be with liver cancer targeting stem cell, to achieve the purpose that effect a radical cure liver cancer.
Background technology
Liver cancer is global 5th common cancer, is also the second largest common killer of China's cancer, 50% or more the whole world
Liver cancer is happened at China.It is clinically one of most common malignant tumour, and incidence has the tendency that rising year by year at present.Liver cancer
It is the vicious behaviour tumour of high invasion, grade malignancy is high, disease progression is fast, and early stage non-evident sympton, causes most of medical
It is later so that it is treated, and difficulty is big, weak curative effect, and case fatality rate is high.Therefore, the prevention and treatment of liver cancer are the one of China's medical research
Item important and pressing task.
The treatment means of liver cancer include mainly surgical intervention (i.e. operation excision), interventional treatment, radiotherapy, Chinese medicine now
Chinese medicine and immunization therapy, and excision of performing the operation is still the preferred option of liver cancer treatment so far.For most of excision that cannot perform the operation
Mid and late liver cancer patient, using a variety of methods, comprehensive, sequential therapy is current most effective measure.But due to individual it is special
Property so that how multiple means select, and how to arrange in pairs or groups to reach optimum curative effect as to solve the problems, such as at present.Currently used for
Only for differentiated tumour cell, it can kill this kind of cell, make the first-line drug needle of liver cancer treatment within a short period of time
Gross tumor volume, which reduces, even to disappear, however is difficult to eradicate the recurrence of liver cancer, cannot be treated from the root cause to liver cancer.Therefore it controls
Tumor recurrence and transfer are still a great problem in liver cancer treatment after treatment.
Tumor stem cell (CSCs), which is sub-fraction present in tumor tissues, has high proliferative capacity and self-renewing
The cell colony of ability is the subgroup that can generate tumour cell, crucial work is played in the generation, transfer, recurrence of tumour
With.Therefore, it is very crucial to the effect of tumor stem cell in the therapeutic process of tumour.Although current researchers are to this
Many strategies are proposed, the elimination of tumor stem cell is still highly difficult.Traditional chemotherapeutics such as Doxorubicin and Japanese yew
Alcohol can kill most tumors cell, but act on extremely weak or even drug resistance to tumor stem cell, so as to cause Tumor Stem in tumour
The raising of cell proportion.Researcher identifies several old drugs (such as salinomycin, diformazan pair by the methods of high flux screening
Guanidine, curcumin, disulfiram) have the function of to resisting tumour stem cells.Salinomycin is chosen in this method as resisting tumour stem cells
Drug is contained in polyethylene glycol-ceramide micella, effectively kills tumor stem cell.
Salinomycin is a kind of broad spectrum antibiotic, is clinically mainly used for preventing and treating the globidiosis of domestic animal, poultry, also normal
As feed addictive in animal productiong medium and long-term applications.Salinomycin (Salinomycin, SAL) is called Salinomycin, excellent element
Essence, Surrey Nuo Maxin, it is a kind of monocarboxylic acid generated by the fermented culture of streptococcus albus (Streptomycesaldus)
Polyethers ionophore type antibiotics have the function of sterilization, antibacterial, anticoccidial, have suppression to most of gram-positive bacterias
It makes and uses.Recent studies have shown that salinomycin can be not only used for the coccidiosis of livestock, also have very to tumor of breast stem cell
Strong lethal effect.2009,《Cell》On publish an article, find the salinomycin energy that is screened from 16,000 compounds
The highly selective human breast carcinoma CSC killed with mouse, and its effect is 100 times higher than classic chemotherapy drug taxol.Subsequently
The study found that salinomycin not only has killing effect to breast cancer CSC, to other many tumor stem cell (liver cancer, prostates
Cancer) all have killing effect.Salinomycin becomes a kind of broad-spectrum anti-tumor stem cell drugs, by the extensive concern of researcher,
Show very strong potential applicability in clinical practice.
Although salinomycin is a kind of effective antitumour stem cell drugs, still have to Common tumors cell to be added
By force, and its toxic side effect is larger, and the clinical application that the two disadvantages result in salinomycin is seriously hampered.Administering drug combinations are
A kind of that Treated with Chemotherapeutic Drugs object is carried out united administering mode, clinical treatment usually needs administering drug combinations to can be only achieved raising chemotherapy
Curative effect of medication and reduction toxic and side.And ceramide (Ceramide) be one kind by sphingol and Fatty acid compositions
Lipid molecular, have significant chemotherapy sensitizing effect.It is multinomial that researches show that it can significantly increase the therapeutic effect of chemotherapeutics,
Our early-stage study results show that Pegylation ceramide (PEG-ceramide) can form micellar structure, and micella is a kind of
Surfactant molecule forms the shape and the spatial arrangement of molecule wherein of special aggregation after its concentration is more than critical value
Nano medication.In aqueous solution, the hydrophilic group of molecule is outwards towards water phase, and hydrophobic group is then with Van der Waals force close-packed arrays.
Salinomycin water solubility is poor, and direct drug injection, stronger to the toxic side effect of body, meanwhile, circulation time in vivo
Also shorter, it is unfavorable for oncotherapy.Therefore there is an urgent need to a kind of carriers can effectively contain free drug salinomycin, high-effective penetrating
Inside tumor and selectively killing tumor cell reduce the drug accumulation of non-target organs, reduce the toxic side effect to body,
Extend circulation time in vivo.It is reported that by ceramide Pegylation, the ability of adriamycin inducing cell can be enhanced.
Polyethylene glycol-ceramide is amphipathic molecule copolymer, has hydrophilic and hydrophobic section, is easy to form small particle micella, therefore
With the possibility for being prepared into carrier and containing salinomycin.And small particle micella (<30nm) monocyte can be not only escaped to gulp down
The effect of biting extends circulation time in vivo, increases accumulation of the drug in solid tumor, also has tumor tissues Thief zone ability, can have
It infiltrates through inside tumor tissues to effect, release drug achievees the purpose that tumors destroyed stem cell.Using PEG-ceramide as carrier
It contains salinomycin and is prepared into targeting and permeability that micella of the grain size less than 30nm can reinforce drug to tumour, eliminate liver cancer
Cell and stem cell.
Chinese patent literature CN104257628A discloses a kind of load salinomycin micella and its preparation method and application, be with
DSPE-PEG2000-CRGDK copolymers are carrier, contain the micella of Salinomycin Sodium.There is no literature reported on PEG- at present
Ceramide is that carrier contains the micella of salinomycin preparation for liver cancer cells and stem cell progress target administration.
Invention content
The purpose of the present invention is to provide a kind of new salinomycins that carries to have the small particle glue of high targeting and penetrating power
Beam and preparation method thereof.It is a further object to provide the micellas to prepare the application in treating liver-cancer medicine.
The present invention selects new type antineoplastic medicine salinomycin, it is contained with PEG-ceramide to the targeting medicine for liver cancer
Object is treated.
Technical scheme of the present invention includes：
One, the preparation of the polyethylene glycol of novel load salinomycin-ceramide micella；
Two, novel carrier micelle penetrates the detection of liver-cancer stem cell ability in vitro；
Three, the external anti-liver cancer and anti-Stem Cell Activity of carrier micelle.
The first aspect of the present invention, provides a kind of polyethylene glycol-ceramide micella carrying salinomycin, which is：With
Polyethylene glycol-ceramide is carrier, contains salinomycin, grain size is the micella of 11 ± 3nm (optimal is 11nm), and the salt is mould
Element is 1 with carrier molar ratio:4.
The second aspect of the present invention provides a kind of preparation side of polyethylene glycol-ceramide micella of above-mentioned load salinomycin
Method includes the following steps：Polyethylene glycol-ceramide is dissolved in chloroform, salinomycin is separately taken, is dissolved in methanol, by two
Kind solution mixes, and decompression rotary evaporation removes organic solvent at 37 DEG C, forms dry film；PH is added into rotary evaporation bottle
7.4 phosphate buffer is simultaneously full of nitrogen, aquation 30min；The polycarbonate membrane for crossing 200nm removes non-encapsulated salinomycin.
Preferably, include the following steps：Polyethylene glycol-ceramide of 5mg is dissolved in 3ml chloroforms, is separately taken
The salinomycin of 0.454mg is dissolved in 1ml methanol, and two kinds of solution are mixed, and decompression rotary evaporation 0.5--2h is (optimal at 37 DEG C
For 2h) organic solvent is removed, form dry film.The phosphate buffer of pH 7.4 is added into rotary evaporation bottle and is full of nitrogen
Gas, aquation 30min.The polycarbonate membrane for crossing 200nm removes non-encapsulated salinomycin.
In order to find best salinomycin encapsulation rate, salinomycin is carried out with PEG-ceramide carrier qualities ratio excellent
Change.Optimization method is：Prepare different mol ratio example (such as 1:2、1:3、1:4) polyethylene glycol-ceramide glue of load salinomycin
Beam surveys its encapsulation rate, show that salinomycin and carrier molar ratio are 1:When 4, the novel carrier micelle salinomycin encapsulation rate of preparation is most
It is good.
In addition, for polyethylene glycol-ceramide and salinomycin have been selected different solvents, polyethylene glycol-nerve respectively
Amide is dissolved in chloroform, and salinomycin is dissolved in methanol, and advantage is by two kinds of organic solvents, chloroforms and methanol with 3：1 ratio
Example mixing, can make salinomycin and carrier material form best dispersed film, the carrier micelle packet obtained after later stage PBS aquations
Envelope rate is higher, and particle size dispersion is evenly.If can also form film with other reagents such as acetonitrile dissolving salinomycin, but dissolved with methanol
As a result more preferably.Hydration process is full of nitrogen, can prevent oxidation of drug；The phosphate buffer of pH 7.4 is selected, gained glue is prepared
Beam uniform particle diameter, and meet animal and human body vivo environment.
The third aspect of the present invention, the polyethylene glycol-ceramide micella for providing the novel load salinomycin of above-mentioned preparation exist
Prepare the application in treatment liver-cancer medicine.
Polyethylene glycol-ceramide micella of the load salinomycin specifically targets differentiated liver-cancer stem cell and common
Liver cancer cells.
(1) present invention prepares the detection of the novel micella of gained high targeting and penetrating power in vitro
Present invention laser confocal microscope detects in liver cancer cells and liver-cancer stem cell to containing fluorescent material micella
Intake ability, to evaluate the outer targeting of glue bundle body and penetrating power.Laser confocal microscope can be to glimmering in liver-cancer stem cell
The weak carry out qualitative analysis of light intensity.
(2) present invention prepares the outer anti-liver cancer and anti-of the novel load salinomycin glue bundle body of gained and liver-cancer stem cell activity
The present invention measures cell in the cell survival rate after the processing of different pharmaceutical concentration, to evaluate drug using CCK-8 methods
With the cytotoxicity of drug-carrying nanometer particle.The survivorship curve of cell after logarithm is simulated, calculate cell IC50 come quantitative comparison its
Cytotoxicity size.
The invention has the advantages that：
Novel load salinomycin polyethylene glycol-ceramide micella of the present invention can improve the treatment of chemotherapeutics salinomycin
Effect can reach the effects of liver cancer targeting stem cell and liver cancer cells while reducing poisonous side effect of medicine, this is that a kind of liver cancer is controlled
The new strategy for the treatment of.It utilizes the advantage of small particle micellar carrier, prepares Nano medication targeting therapy on tumor, has wide application
Foreground.
Description of the drawings
Fig. 1 film dispersion methods prepare novel load medicine PEG-ceramide micellas.
Fig. 2 carry the characterization of polyethylene glycol-ceramide micella of salinomycin, wherein A is the aquation particle diameter distribution of micella
Figure；B is the aquation potential image of micella；C is the transmission electron microscope picture of micella.
The screening of Fig. 3 salinomycins and polyethylene glycol-ceramide collaboration ratio.
The fluorescent value intensity of Fig. 4 hepatocellular carcinoma H22s and stem cell intake PECF.
Fig. 5 laser co-focusings detect the intake ability of liver cancer and liver-cancer stem cell to micella, wherein A takes the photograph for liver cancer cells
Take novel load fluorescent material micella；B is that liver-cancer stem cell absorbs novel load fluorescent material micella；C is that liver-cancer stem cell is unicellular
Suspension absorbs novel load fluorescent material micella.
Fig. 6 carry the half-inhibition concentration of salinomycin micella and free salinomycin to liver cancer cells and liver-cancer stem cell
(IC50), wherein A is the half-inhibition concentration for carrying salinomycin micella and free salinomycin to liver cancer cells；B is to carry salinomycin glue
The half-inhibition concentration of beam and free salinomycin to liver-cancer stem cell.
Specific implementation mode
It elaborates to specific implementation mode provided by the invention with reference to embodiment.
Material and instrument
Laser granulometry, Malvern Instr Ltd. of Britain；
R series rotary evaporators, Shensheng Science ＆ Tech. Co., Ltd., Shanghai；
CRGDK line peptides, gill biochemistry Co., Ltd；
1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy
(polyethylene glycol) -2000] (ammonium salt) (DSPE-mPEG2000), Avanti Polar
Lipids；
PEG-ceramide, Shanghai Yan Yi Bioisystech Co., Ltd；
Salinomycin, Sigma Co., USA；
HPLC chromatogram purity>93.8%；
Bag filter (molecular cut off 1000), upper sea green bird Biological Development Co., Ltd；
Phosphate buffer (PBS), Hyclone companies of the U.S.；
Acetonitrile and tetrahydrofuran are chromatographically pure, other reagents are that analysis is pure；
Basic fibroblast growth factor (bFGF), prospec companies of Israel；
Endothelial growth factors (EGF), insulin, prospec companies of Israel；
Fetal calf serum, pancreatin, green chain be dual anti-, B27 additives, Gibico companies of the U.S.；
Other chemical reagent are purchased from Shanghai Chinese medicines group；
Du Shi phosphate buffers (D-PBS), Thermo companies of the U.S.；
A ten thousandth electronic balance AL104, Mei Teletuo benefit company；
Ten a ten thousandth electronic balance MS205DU, Mei Teletuo benefit companies；
Transmission electron microscope JEM2100F, Japanese JEOL companies；
Zetasizer nano ZS laser particle size analyzers, Malvern company of Britain；
Shimadzu high performance liquid chromatograph LC-20A, Japanese Shimadzu Corporation.
Embodiment 1:Carry the preparation of polyethylene glycol-ceramide micella of salinomycin
5mg PEG-ceramide are dissolved in 3ml chloroforms, 0.454mg salinomycins is separately taken to be dissolved in 1ml methanol, it will
Above two solution mixes, and decompression rotary evaporation 2h removes organic solvent at 37 DEG C, forms dry film.2mL is added into bottle
The phosphate buffer of pH 7.4 is simultaneously full of nitrogen, aquation 30min.It crosses 200nm polycarbonate membranes and removes non-encapsulated salinomycin
(Fig. 1).
For the micella grain size prepared by film dispersion method at 11nm (Fig. 2A), transmission electron microscope (Fig. 2 C) shows system of the present invention
Standby novel carrier micelle is spherical shape, and has typical nucleocapsid structure.It is novel to show prepared by the present invention by the experiment
PEG-ceramide self-assembled micelles have specific microstructure.
Fact Example 2：The determination of the carrier micelle of optimization ratio
(1) cell inoculation：Hepatoma Hep G 2 cells are inoculated in 96 orifice plates；
(2) experiment packet and medicine preparation：Experiment is divided into 1:2,1:3,1:4 (salinomycins：Polyethylene glycol-ceramide
Molar ratio) 3 groups, the carrier micelle of three kinds of ratios is prepared, respectively 3 doubling dilution, nine concentration successively；
(3) dosing：The drug of each concentration 100uL of each group is added 96 orifice plates respectively, is placed in 5% by 12h after cell is adherent
CO2, 37 DEG C of incubators incubation 48h；
(4) add CCK-8, be placed in microplate reader and survey its OD value, calculate cell killing efficiency；
(5) medication combined index-cell killing efficiency collection of illustrative plates is drawn：Compusyn softwares are relied on, calculates and draws two kinds
Killing-efficiency (Fraction affected, fa) of association index (Combination Index, the CI) value of drug to cell
Mapping, screening obtain salinomycin (SAL) and cooperate with ratio to HepG2 cells with polyethylene glycol-ceramide (PEG-ceramide)
Example.
By above-mentioned experiment, we obtain the CI-fa curves such as Fig. 3, it is known that 1:2 and 1:There is more preferably two medicines when 4
Synergistic killing effect.
Embodiment 3:Laser co-focusing detects liver cancer cells and liver-cancer stem cell to containing the intake energy of fluorescent material micella
Power
(1) preparation containing fluorescent material micella.400 μ g PECF fluorescent materials are dissolved in 1ml methanol, by 5mg
PEG-ceramide is dissolved in 3ml chloroforms, and the micella containing fluorescent material is prepared into using film dispersion method.
(2) liver cancer cells detect the intake ability of fluorescent material micella：Paving 5 × 105A HepG2Cell is copolymerized in laser
In burnt ware, 37 DEG C are placed in, 5%CO2Incubator in overnight incubation.After cell is adherent, reject culture medium is separately added into blank training
Support base (Control), free fluorescent material PECF (Free PECF), the polyethylene glycol-ceramide micellar solution for carrying PECF
(PECF-PEG-CRM-M) and carry PECF DSPE-PEG micellar solutions (PECF-DSPE-PEG-M).Drug is incubated 2 at 37 DEG C
After hour, twice with PBS rinses, add DAPI to dye 5min, PBS is added to wash twice, is eventually adding 500 μ LPBS and cell is resuspended, swash
Light copolymerization is burnt to observe its fluorescence intensity.
(3) liver-cancer stem cell detects the intake ability of fluorescent material micella：Take a certain amount of microsphere and microsphere list
Cell suspension is separately added into blank cultures, free fluorescent material PECF, the poly- second two for carrying PECF in laser co-focusing ware
Alcohol-ceramide micellar solution and the DSPE-PEG micellar solutions for carrying PECF, are subsequently placed at 37 DEG C, 5%CO2Incubator in incubate
It educates 2 hours, twice with PBS centrifuge washings, adds DAPI to dye 5min, PBS is added to wash twice, be eventually adding 0.5ml PBS transfers
To observing its fluorescence intensity in laser co-focusing ware.
By comparing intracellular Fluorescence brightness in liver cancer cells and stem cell fluorescent value (see Fig. 4) and laser co-focusing (see
Fig. 5), it can be seen that fluorescent value is apparently higher than its control group in liver cancer cells and liver-cancer stem cell.And the fluorescent value of liver-cancer stem cell
And fluorescent brightness is apparently higher than liver cancer cells, illustrates that liver-cancer stem cell is more stronger than liver cancer cells to the intake ability of micella.
Embodiment 4:Carry the activity analysis of the outer anti-liver cancer and anti-of salinomycin glue bundle body
(1) for adherent HepG2Cell strain
By the HepG of logarithmic phase2Cell is digested through pancreatin, single cell suspension is made with serum-containing media resuspension, adjustment is thin
Born of the same parents' density is to 3 × 104A/mL is inoculated in the density in 3000/hole in 96 orifice plates, i.e., the unicellular outstanding of 100uL is added per hole
Liquid, the cell being inoculated with is in 37 DEG C, 5%CO2Under conditions of overnight incubation, wait for cell growth to proper density.
After cell pellet overnight is adherent, every hole culture medium is abandoned in suction, and it is diluted to be separately added into 100 μ l culture mediums then to each hole
The polypeptide drug-loaded micelle solution of various concentration, concentration are respectively 333.333,111.111,37.037,12.346,4.115,1.372,
0.457,0.152,0.051 μM, 96 orifice plates are placed in carbon dioxide constant incubator relaying by 3 secondary orifices of each concentration after dosing
Continuous culture 48h.Set the blank control wells for being not added with cell and the negative control hole without any processing simultaneously.It is small after incubation 48h
Supernatant is abandoned in heart suction, and the CCK-8 solution that 100 μ l a concentration of 10% are added per hole is incubated 2h again.Microplate reader is subsequently placed in 450nm
Measure each hole OD values.Cells survival rate (%)=(experimental group OD values-blank control group OD values)/(negative control group OD values-sky
White group control OD values) × 100.
(2) for the HepG2 stem cells of suspension
By the HepG of logarithmic phase2Single cell suspension is made after pancreatin digests in cell, is resuspended with serum free medium, obtains list
Cell suspension is inoculated in the density in 3000/hole in 96 orifice plates, i.e., the single cell suspension of 100uL is added per hole, has been inoculated with
Cell is in 37 DEG C, 5%CO2Under conditions of cultivate for 24 hours, wait for cell growth to proper density.
The 100 diluted drugs of μ L culture mediums are separately added into each hole, final concentration is respectively 111.111,37.037,
12.346,4.115,1.372,0.457,0.152,0.051,0.017 μM, 3 secondary orifices are set per hole, carbon dioxide is returned after dosing
Continue to cultivate 48h in incubator.Set the blank control wells (fresh culture) for being not added with cell and without any processing simultaneously
Negative control hole.After being incubated 48h, 20 μ lCCK-8 solution are added to every hole and are incubated 4h again.Microplate reader is subsequently placed in survey in 450nm
Fixed each hole OD values.Cells survival rate (%)=(experimental group OD values-blank control group OD values)/(negative control group OD values-blank
Control group OD values) × 100%
Fig. 6 shows free salinomycin, novel load salinomycin micella and traditional carrier micelle to HepG2Cell and Tumor Stem
Cytotoxicity can obtain following result：
(1) salinomycin, novel load salinomycin micella and traditional carrier micelle are to HepG2The toxicity of cell and tumor stem cell
With concentration dependent, increased with the concentration of salinomycin, cell survival rate is remarkably decreased.
(2) compared with HepG2Attached cell, HepG2Tumor stem cell has higher sensibility to salinomycin and its micella,
Show the effect of salinomycin has more preferably the treatment of liver-cancer stem cell.
(3) no matter novel load salinomycin micella is to HepG2The inhibiting effect of attached cell or stem cell is better than free
Salinomycin group illustrates that the novel carrier micelle can enhance inhibition and the lethal effect to liver cancer cells.
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry
Personnel are it should be appreciated that the present invention is not limited to the above embodiments, and the above embodiments and description only describe this
The principle of invention, various changes and improvements may be made to the invention without departing from the spirit and scope of the present invention, these changes
Change and improvement all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and its
Equivalent defines.
Claims (4)
1. a kind of polyethylene glycol-ceramide micella carrying salinomycin, which is characterized in that the micella is：With polyethylene glycol-nerve
Amide is carrier, contains salinomycin, and grain size is the micella of 11 ± 3nm, and the salinomycin is 1 with carrier molar ratio:4；It is made
Preparation Method includes the following steps：Polyethylene glycol-ceramide is dissolved in chloroform, salinomycin is separately taken, is dissolved in methanol, it will
Two kinds of solution mix, and decompression rotary evaporation removes organic solvent at 37 DEG C, forms dry film；PH is added into rotary evaporation bottle
7.4 phosphate buffer is simultaneously full of nitrogen, aquation 30min；The polycarbonate membrane for crossing 200nm removes non-encapsulated salinomycin.
2. a kind of preparation method for the polyethylene glycol-ceramide micella carrying salinomycin, which is characterized in that the micella is：With poly-
Ethylene glycol-ceramide is carrier, contains salinomycin, and grain size is the micella of 11 ± 3nm, the salinomycin and carrier molar ratio
It is 1:4；Preparation method includes the following steps：Polyethylene glycol-ceramide is dissolved in chloroform, salinomycin is separately taken, is dissolved
In methanol, two kinds of solution are mixed, decompression rotary evaporation removes organic solvent at 37 DEG C, forms dry film；It is steamed to rotation
It sends out the phosphate buffer that pH 7.4 is added in bottle and is full of nitrogen, aquation 30min；Cross the polycarbonate membrane removal of 200nm not
The salinomycin of encapsulating.
3. a kind of polyethylene glycol-ceramide micella as described in claim 1 carrying salinomycin is preparing treatment liver-cancer medicine
In application.
4. polyethylene glycol-ceramide the micella according to claim 3 for carrying salinomycin is in preparing treatment liver-cancer medicine
Application, which is characterized in that polyethylene glycol-ceramide micella of the load salinomycin targets differentiated liver-cancer stem cell
With common liver cancer cells.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7422902B1 (en) * | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| CN104257628A (en) * | 2014-09-15 | 2015-01-07 | 中国人民解放军第二军医大学 | Salinomycin-loaded micelle as well as preparation method and application thereof |
-
2015
- 2015-10-30 CN CN201510725278.XA patent/CN105250238B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7422902B1 (en) * | 1995-06-07 | 2008-09-09 | The University Of British Columbia | Lipid-nucleic acid particles prepared via a hydrophobic lipid-nucleic acid complex intermediate and use for gene transfer |
| CN104257628A (en) * | 2014-09-15 | 2015-01-07 | 中国人民解放军第二军医大学 | Salinomycin-loaded micelle as well as preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| Co-delivery of doxorubicin and PEGylated C16-ceramide by nanoliposomes for enhanced therapy against multidrug resistance;Xiao Su et al;《Nanomedicine》;20150618;第10卷(第13期);第2033-2050页，尤其是第2039页右栏第1段，第2046页左栏倒数第2段 * |
| 穿膜肽修饰盐霉素胶束的制备与表征;毛骁丽等;《中国新药杂志》;20141231;第23卷(第23期);第2812-2816页，尤其是第2813页第2、3.1节，第2815页第4节 * |
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