CN108403632A - A kind of temperature ＆ reduction sensitive carries the preparation method of medicine Pluronic F127 base nano-micelles - Google Patents
A kind of temperature ＆ reduction sensitive carries the preparation method of medicine Pluronic F127 base nano-micelles Download PDFInfo
- Publication number
- CN108403632A CN108403632A CN201810218275.0A CN201810218275A CN108403632A CN 108403632 A CN108403632 A CN 108403632A CN 201810218275 A CN201810218275 A CN 201810218275A CN 108403632 A CN108403632 A CN 108403632A
- Authority
- CN
- China
- Prior art keywords
- pluronic
- micelles
- medicine
- temperature
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- 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
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- A61K31/585—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to the preparation methods that a kind of temperature ＆ reduction sensitives carry medicine Pluronic F127 base nano-micelles, including：Prepared by the HOOC F127 COOH of carboxylated, prepared by the HOOC F127 COOH nano-micelles for being loaded with Bufalin, prepared by crosslinked load medicine Pluronic F127 base nano-micelles.Pluronic F127, maleic anhydride and the 2-aminoethyl disulfide dihydrochloride that the present invention uses all are the extraordinary biomaterials of biocompatibility, will not generate toxicity to body；The novel medicine carrying material of the present invention has the characteristics that the characteristics of microenvironment realizes reduced form release in the temperature sensitive drugloading rate for improving micella and response cancer cell, can be used for antitumor research, there is good practical value.
Description
Technical field
The invention belongs to tumor microenvironment responsive nano field of material preparation, more particularly to a kind of temperature ＆ restores Lazer
Sense carries the preparation method of medicine Pluronic F127 base nano-micelles.
Background technology
Bufalin is a kind of cardioactive steroid, it is that have anti-swell in traditional Chinese medicine cinobufagin injection
One of the main active of tumor effect.Bufalin it is verified that have very strong antitumous effect, including：Inhibit cancer cell
Proliferation, induce Carcinoma cell differentiation, cancer cell specific induction of apoptosis to destroy cell growth cycle, inhibit tumor angiogenesis etc..Together
When, Bufalin takes part in complicated cell signaling pathway, realizes the selectivity control to cancer cell multiplication, normal cell
Unaffected, to realize the targeting killing to cancer cell.Bufalin be also steroid receptors co-activation factor S RC-1 and
The inhibitor of SRC-3, the growth of cancer cell can be inhibited with the concentration of nanomole grade by imparting Bufalin.
Triblock copolymer Pluronic F127 as medicament without physiological activity, no hemolytic, to no skin irritation,
Small toxicity is ratified by U.S. Food and Drug Administration, since it has the critical micelle concentration of temperature-responsive,
PluronicF127 variations based on temperature are easy to be self-assembly of micella or disintegration.Based on this characteristic, Pluronic F127
The micella of formation is used for containing a series of hydrophobic drug.In order to improve the colloidal stability of carrier micelle, drug is prevented not
The release in advance of tumour target position is reached, cystamine can be used to carry out micella surface-crosslinked, not only increase micella in this way
Stability, while responding the Targeting delivery that the high reduction potential of cancer cell realizes drug.
Invention content
Technical problem to be solved by the invention is to provide a kind of temperature ＆ reduction sensitives to carry medicine Pluronic F127 bases
The preparation method of nano-micelle, this method is easy to operate, and reaction condition is mild, and the load medicine of micella is improved by temperature sensitivity
Amount, reduction sensitivity realize the Targeting delivery of drug, and prepared sensitive carrier micelle shows targeted therapy of cancer
Wide foreground.
A kind of temperature ＆ reduction sensitives of the present invention carry the preparation method of medicine Pluronic F127 base nano-micelles, specifically
Steps are as follows：
(1) maleic anhydride is added in the Pluronic F127 solution containing pyridine, is reacted under nitrogen protection, purified,
Dialysis, freeze-drying, obtains the HOOC-F127-COOH of carboxylated, the wherein molar ratio of maleic anhydride and Pluronic F127
It is 8:1-12:1；
(2) by HOOC-F127-COOH and Bufalin Bufalin in step (1) with mass ratio be 5:1-15:1 be dissolved in it is molten
In agent, stirring evaporates solvent, obtains polymer medicine film, with deionized water aquation, is vortexed, continues to be stirred to react under the conditions of 4 DEG C
Night dialyses under the conditions of 37 DEG C, is freeze-dried, obtains the HOOC-F127-COOH nano-micelles for being loaded with Bufalin, wherein Bufalin
Mass ratio with solvent is 1:500-1:300, HOOC-F127-COOH and deionized water mass ratio be 1:50-1:30；
(3) the HOOC-F127-COOH nano-micelles for being loaded with Bufalin in step (2) are distributed in solvent, NHS is added
And EDCHCl, it activates under nitrogen protection overnight, 2-aminoethyl disulfide dihydrochloride reaction is then added, dialyses, freeze-drying is crosslinked
Load medicine Pluronic F127 base nano-micelles, HOOC-F127-COOH, NHS, EDCHCl and cystamine wherein in step (2)
The molar ratio of dihydrochloride is 1:1-3:1-3:1, the mass ratio of HOOC-F127-COOH and solvent is 1 in step (2):300-1:
200。
The solvent of the Pluronic F127 solution containing pyridine is toluene, the volume ratio of toluene and pyridine in the step (1)
It is 18:1-22:1.
The temperature reacted in the step (1) is room temperature, and the time of reaction is 7-9h.
It is purified in the step (1) and is specially：It is dissolved with methanol, then ice ether is used to precipitate, repeated 3-4 times.
Solvent is methanol in the step (2).
Mixing time is 0.5h in the step (2)；The temperature of deionized water is 40 DEG C；Vortex time is 10min.
It dialyses in the step (1), (2), (3) and is specially：The bag filter for being 7000 with molecular cut off is in pH=7.4
PBS buffer solution in dialyse -72h for 24 hours.
Solvent is PBS buffer solution in the step (3)；PH value is adjusted to 5 using the hydrochloric acid weak solution of 1%v/v when reaction
~6.
Reaction temperature is room temperature in the step (3), and the reaction time is for 24 hours.
The crosslinked drug delivery for carrying medicine Pluronic F127 base nano-micelles and being applied to cancer cell in the step (3).
HOOC-F127-COOH is self-assembly of micella under the conditions of 4 DEG C in the present invention, at this temperature, micella tool
There are highest permeability, magnetic stirrer over night to improve drugloading rate；37 DEG C under the conditions of micella shrink so that drug tightly
It is wrapped in inside micella；Activator EDC is added, using 2-aminoethyl disulfide dihydrochloride to the HOOC-F127- of load Bufalin (Bufalin)
COOH nano-micelles carry out surface-crosslinked.
Advantageous effect
(1) Pluronic F127, maleic anhydride and the 2-aminoethyl disulfide dihydrochloride that use of the present invention be all biocompatibility very
Good biomaterial will not generate toxicity to body；
(2) the triblock copolymer HOOC-F127-COOH that the present invention synthesizes has temperature sensitivity, and at 4 DEG C, grain size becomes
Big and permeability highest, therefore the drugloading rate and encapsulation rate of micella can be improved at this temperature, when temperature is increased to 37 DEG C
When, the grain size of micella is reduced rapidly, and structure becomes relatively compact, therefore Bufalin is effectively tightly wrapped in micella core portion；
(3) present invention is crosslinked carrier micelle using the method for post-crosslinking using cystamine, not only increases load medicine body
The colloidal stability of system prevents the release in advance of the drug in cyclic process, and due to the presence of disulfide bond in cystamine, assigns
Nanometer medicine-carried system reduction-sensitive keeps stablizing under the normal physiological context, is absorbed by cancer cell when reaching tumor locus
Afterwards, due to the higher glutathione of concentration (GSH) in cancer cell so that disulfide bonds, micella decompose, drug release, effect
In nucleus, apoptosis occurs for cancer cell.
Description of the drawings
Fig. 1 is that crosslinked medicament-carried nano micelle preparation process of the invention and crosslinked medicament-carried nano micelle are used for cancer cell medicine
The procedure chart of object delivering；
Fig. 2 is HOOC-F127-COOH micellas (a) and the crosslinked HOOC-F127-COOH micellas (b) of cystamine in embodiment 2
Change of size curve at 4 DEG C and 37 DEG C；
Fig. 3 is the HOOC-F127-COOH micellas and crosslinking HOOC-F127-COOH micellas that Bufalin is loaded in embodiment 3
Release profiles in PBS, the PBS containing glutathione respectively.
Specific implementation mode
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention
Rather than it limits the scope of the invention.In addition, it should also be understood that, after reading the content taught by the present invention, people in the art
Member can make various changes or modifications the present invention, and such equivalent forms equally fall within the application the appended claims and limited
Range.
Embodiment 1
(1) 386mg maleic anhydrides are added in the 20mL toluene solutions of Pluronic F127 (5g) of the pyridine containing 1mL,
It under the protection of nitrogen, reacts at room temperature 8 hours, is dissolved with methanol, then ice ether is used to precipitate, repeat 3-4 times, then with retention
The bag filter that molecular weight is 7000 is dialysed 3 days in the PBS buffer solution of pH=7.4, and freeze-drying obtains the HOOC- of carboxylated
F127-COOH。
(2) HOOC-F127-COOH the and 20mg Bufalins Bufalin of 200mg carboxylated in step (1) is dissolved into
In 10mL methanol, to being completely dissolved, rotary evaporation to solvent volatilizees magnetic agitation 0.5h completely, obtains polymer medicine film, uses
The deionized water aquation of 40 DEG C of 10mL, be then vortexed 10min, the magnetic stirrer over night at 4 DEG C, is with interception at 37 DEG C
7000 bag filter is dialysed 2 days in the PBS buffer solution of pH=7.4, and freeze-drying obtains the HOOC- for being loaded with Bufalin
F127-COOH nano-micelles.
(3) the HOOC-F127-COOH nano-micelles that 200mg in step (2) is loaded with to Bufalin are distributed to 50mL PBS
In buffer solution, 6.9mg NHS and 11.5mg EDCHCl are added, under nitrogen protection, reaction is activated overnight carboxyl, is then added
6.8mg 2-aminoethyl disulfide dihydrochlorides adjust pH value to 5-6 using the hydrochloric acid weak solution of 1% (v/v), react at room temperature for 24 hours, with retention
Amount is dialysed for 24 hours for 7000 bag filter in the PBS buffer solution in pH=7.4, and freeze-drying obtains crosslinked medicament-carried nano glue
Shu Fenmo.
Embodiment 2
(1) the HOOC-F127-COOH micellas and the crosslinked HOOC- of cystamine for not carrying medicine are prepared according to the method for embodiment 1
F127-COOH micellas.By the crosslinked HOOC-F127-COOH micellas difference of the HOOC-F127-COOH micellas and cystamine that do not carry medicine
It is made into the solution of a concentration of 2mg/mL with the PBS of pH=7.4, then surveys its water dynamic particle size at 4 DEG C and 37 DEG C respectively.
Its water dynamic particle size is surveyed at 4 DEG C and 37 DEG C for (2) two kinds of micellas as shown in Fig. 2, HOOC-F127-COOH blank glue
Beam is respectively 281 ± 5nm, 20 ± 4nm in the grain size of 4 DEG C and 37 DEG C；Blank micella after cystamine crosslinking is in 4 DEG C and 37 DEG C of grain
Diameter is respectively 35 ± 4nm, 21 ± 3nm.The result shows that HOOC-F127-COOH has temperature sensitivity, at 4 DEG C, grain size becomes
Greatly, permeability improves, to improve the drugloading rate and encapsulation rate of drug.After crosslinking, change of size of the micella in 4 DEG C and 37 DEG C
Less, show that the crosslinking of cystamine improves the stability of micella.
Embodiment 3
(1) the HOOC-F127-COOH nano-micelles for being loaded with Bufalin in 20mg embodiments 1 and crosslinked load medicine is respectively taken to receive
Rice glue beam is dissolved in respectively in the PBS that 1mL pH are 7.4, is then charged into the bag filter that molecular cut off is 7000, is then divided
Not Jin Ru a concentration of 10mM of 19mL glutathione GSH PBS (pH=7.4) or the PBS buffer solution without glutathione pH=7.4
In.
(2) by above-mentioned delivery system be transferred to 37 DEG C of rotating speeds be 100rpm constant-temperature table in 48h, respectively 0.25h,
0.5h, 1h, 2h, 4h, 8h, 12h, for 24 hours, 48h take 1mL to survey its ultraviolet absorptivity at 298nm, then again supply 1mL it is identical
The PBS buffer solution of condition collects data and calculates drug release situation.
Bufalin in (3) two kinds of carriers is as shown in Figure 3 with or without the release profiles under glutathione environment.In 48h
Afterwards, it carries cumulative release amounts of the final Bufalin of medicine crosslinking micella in PBS sustained-release liquids and there was only 33 ± 1.1%.However in paddy Guang
Burst size is up to 69 ± 1.2% in the PBS environment that sweet peptide concentration is 10mM.Cumulative release after uncrosslinked carrier micelle 48h
Rate is 51 ± 1.1%, and the presence of glutathione influences very little to the release of its Bufalin.The result shows that the load medicine of preparation
Crosslinking micella has the sensitive characteristic of reduction, is advantageously implemented Targeting delivery of the drug in cancer cell, reduces the poison to body
Side effect.
Embodiment 4
(1) it is put into coverslip in 24 porocyte culture plates, and plants into L929 cells or HepG2 cells, it is close per hole cell
Degree is about 30,000, and supplies the culture solution of every hole 1mL, in 5%CO2Under conditions of cultivated for 24 hours in incubator.
Old culture medium is outwelled within (2) second days, Bufalin, uncrosslinked load FITC containing 20 μ g/mL FITC labels is added
The PBS solution of the 100 μ L of micella of the micella of the Bufalin of label and the crosslinked Bufalin for carrying FITC labels, and supply
900 μ L fresh cultures are incubated 2h.
(3) culture solution containing material is sucked, PBS is used in combination to rinse, adds and fixes 15min at 4 DEG C of the glutaraldehyde of 1ml 2.5%.
(4) glutaraldehyde is sucked, PBS is used in combination to rinse, 10 μ g/mL Hoescht 33342 of 1mL is added to dye 15min.
(5) Hoescht 33342 is sucked, PBS is used in combination to rinse, coverslip is taken out, drips fluorescence sealer, is placed in load
On slide, laser confocal microscope detection is carried out.
(6) laser confocal microscope of the free Bufalin or different carrier micelles to L929 cells and HepG2 cells
Testing result shows：The FITC fluorescence intensities of L929 cells after material is hatched are very weak, however, after carrier micelle is hatched
HepG2 it is intracellular FITC fluorescence intensities it is higher, the HepG2 cells shows through cystamine crosslinked carrier micelle hatching have gone out most
Strong intracellular FITC intensity illustrates that carrier micelle is presented with liver cancer cells certain targeting selectivity.
Claims (10)
1. a kind of temperature ＆ reduction sensitive carries the preparation method of medicine Pluronic F127 base nano-micelles, it is as follows：
(1) maleic anhydride is added in the Pluronic F127 solution containing pyridine, is reacted under nitrogen protection, purified, thoroughly
Analysis, freeze-drying, obtains the HOOC-F127-COOH of carboxylated, the molar ratio of wherein maleic anhydride and Pluronic F127 is
8:1-12:1；
(2) by HOOC-F127-COOH and Bufalin Bufalin in step (1) with mass ratio be 5:1-15:1 is dissolved in solvent
In, stirring evaporates solvent, obtains polymer medicine film, with deionized water aquation, is vortexed, continues to be stirred to react under the conditions of 4 DEG C
Night dialyses under the conditions of 37 DEG C, is freeze-dried, obtains the HOOC-F127-COOH nano-micelles for being loaded with Bufalin, wherein Bufalin
Mass ratio with solvent is 1:500-1:300, HOOC-F127-COOH and deionized water mass ratio be 1:50-1:30；
(3) the HOOC-F127-COOH nano-micelles that Bufalin is loaded in step (2) are distributed in solvent, be added NHS and
EDCHCl is activated under nitrogen protection overnight, 2-aminoethyl disulfide dihydrochloride reaction is then added, dialyses, and freeze-drying obtains crosslinked
Carry medicine Pluronic F127 base nano-micelles, HOOC-F127-COOH, NHS, EDCHCl and cystamine two wherein in step (2)
The molar ratio of hydrochloride is 1:1-3:1-3:1, the mass ratio of HOOC-F127-COOH and solvent is 1 in step (2):300-1:
200。
2. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the preparation of medicine Pluronic F127 base nano-micelles
Method, which is characterized in that the solvent of the Pluronic F127 solution containing pyridine is toluene, toluene and pyridine in the step (1)
Volume ratio be 18:1-22:1.
3. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the preparation of medicine Pluronic F127 base nano-micelles
Method, which is characterized in that the temperature reacted in the step (1) is room temperature, and the time of reaction is 7-9h.
4. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the preparation of medicine Pluronic F127 base nano-micelles
Method, which is characterized in that in the step (1) purification be specially：It is dissolved with methanol, then ice ether is used to precipitate, repeat 3-4
It is secondary.
5. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the preparation of medicine Pluronic F127 base nano-micelles
Method, which is characterized in that solvent is methanol in the step (2).
6. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the preparation of medicine Pluronic F127 base nano-micelles
Method, which is characterized in that mixing time is 0.5h in the step (2)；The temperature of deionized water is 40 DEG C；Vortex time is
10min。
7. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the preparation of medicine Pluronic F127 base nano-micelles
Method, which is characterized in that dialysing in the step (1), (2), (3) is specially：The bag filter for being 7000 with molecular cut off
Dialyse -72h for 24 hours in the PBS buffer solution of pH=7.4.
8. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the preparation of medicine Pluronic F127 base nano-micelles
Method, which is characterized in that solvent is PBS buffer solution in the step (3)；It is adjusted using the hydrochloric acid weak solution of 1%v/v when reaction
PH value is to 5~6.
9. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the preparation of medicine Pluronic F127 base nano-micelles
Method, which is characterized in that reaction temperature is room temperature in the step (3), and the reaction time is for 24 hours.
10. a kind of temperature ＆ reduction sensitive described in accordance with the claim 1 carries the system of medicine Pluronic F127 base nano-micelles
Preparation Method, which is characterized in that crosslinked load medicine Pluronic F127 base nano-micelles are applied to cancer cell in the step (3)
Drug delivery.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810218275.0A CN108403632A (en) | 2018-03-16 | 2018-03-16 | A kind of temperature ＆ reduction sensitive carries the preparation method of medicine Pluronic F127 base nano-micelles |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810218275.0A CN108403632A (en) | 2018-03-16 | 2018-03-16 | A kind of temperature ＆ reduction sensitive carries the preparation method of medicine Pluronic F127 base nano-micelles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108403632A true CN108403632A (en) | 2018-08-17 |
Family
ID=63131754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810218275.0A Pending CN108403632A (en) | 2018-03-16 | 2018-03-16 | A kind of temperature ＆ reduction sensitive carries the preparation method of medicine Pluronic F127 base nano-micelles |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108403632A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113350293A (en) * | 2021-06-01 | 2021-09-07 | 复旦大学 | Hybrid single micelle nanoparticle for encapsulating functional molecules and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105131182A (en) * | 2015-09-06 | 2015-12-09 | 山东大学 | Pluronic-poly(beta-amino ester) polymer and synthesis and application methods |
-
2018
- 2018-03-16 CN CN201810218275.0A patent/CN108403632A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105131182A (en) * | 2015-09-06 | 2015-12-09 | 山东大学 | Pluronic-poly(beta-amino ester) polymer and synthesis and application methods |
Non-Patent Citations (8)
| Title |
|---|
| ESMAEIL MOAZENI，等: "Preparation and evaluation of inhalable itraconazole chitosan based polymeric micelles", 《JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
| MOHAMED A. EL-GENDY，等: "Olmesartan medoxomil-loaded mixed micelles: Preparation, characterization and in-vitro evaluation", 《FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
| NANNAN GAO，等: "Injectable shell-crosslinked F127 micelle/hydrogel composites with pH and redox sensitivity for combined release of anticancer drugs", 《CHEMICAL ENGINEERING JOURNAL》 * |
| YONG-YONG LI，等: "Pluronic F127 nanomicelles engineered with nuclear localized functionality for targeted drug delivery", 《MATERIALS SCIENCE AND ENGINEERING C》 * |
| 串星星，等: "还原响应型高载药量普朗尼克F127 聚合物胶束的制备", 《中国药房》 * |
| 张传宝，等: "Pluronic F127 胶束的载药、固化及其片剂的溶出度", 《中国药科大学学报》 * |
| 殷佩浩，等: "《中药蟾酥的研究与应用》", 31 December 2014, 第二军医大学出版社 * |
| 黄志军，等: "薄膜水化法制备长春西汀胶束的工艺研究", 《中药材》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113350293A (en) * | 2021-06-01 | 2021-09-07 | 复旦大学 | Hybrid single micelle nanoparticle for encapsulating functional molecules and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yan et al. | A pH-responsive drug-delivery platform based on glycol chitosan–coated liposomes | |
| Qian et al. | pH-sensitive strontium carbonate nanoparticles as new anticancer vehicles for controlled etoposide release | |
| Zhang et al. | Solid lipid nanoparticles modified with stearic acid–octaarginine for oral administration of insulin | |
| Shi et al. | ε-Polylysine and next-generation dendrigraft poly-L-lysine: chemistry, activity, and applications in biopharmaceuticals | |
| Tekade et al. | Surface-engineered dendrimers for dual drug delivery: a receptor up-regulation and enhanced cancer targeting strategy | |
| Sawant et al. | Multifunctionality of lipid-core micelles for drug delivery and tumour targeting | |
| Liu et al. | Evaluation of the efficacy of paclitaxel with curcumin combination in ovarian cancer cells | |
| Zhou et al. | Redox-and MMP-2-sensitive drug delivery nanoparticles based on gelatin and albumin for tumor targeted delivery of paclitaxel | |
| CN103143027A (en) | Preparation of hyaluronic-acid-based double-targeting nano-composite medicament and application of double-targeting nano-composite medicament | |
| Zhang et al. | Preparation of chitosan-polyaspartic acid-5-fluorouracil nanoparticles and its anti-carcinoma effect on tumor growth in nude mice | |
| CN109223729B (en) | Material with thioketal bond bonding adriamycin and polyphosphate ester and preparation method and application thereof | |
| Li et al. | Antitumor drug Paclitaxel-loaded pH-sensitive nanoparticles targeting tumor extracellular pH | |
| Kim et al. | Low-molecular-weight methylcellulose-based thermo-reversible gel/pluronic micelle combination system for local and sustained docetaxel delivery | |
| Zhang et al. | Nanopurpurin-based photodynamic therapy destructs extracellular matrix against intractable tumor metastasis | |
| Lai et al. | A novel micelle of coumarin derivative monoend-functionalized PEG for anti-tumor drug delivery: in vitro and in vivo study | |
| CN112876578B (en) | Amphiphilic glucan derivative carrier targeting tumor-associated fibroblasts, and preparation and application of pharmaceutical composition of amphiphilic glucan derivative carrier | |
| CN105566511B (en) | Electric charge overturns pulullan polysaccharide derivative and its preparation method and use | |
| CN106729727A (en) | Reduction response type magnetic nano-carrier of targeting ligand modification and preparation method thereof | |
| Kiew et al. | Preparation and characterization of an amylase-triggered dextrin-linked graphene oxide anticancer drug nanocarrier and its vascular permeability | |
| Wang et al. | Self-crosslinked keratin nanoparticles for pH and GSH dual responsive drug carriers | |
| Zhao et al. | Using acoustic cavitation to enhance chemotherapy of DOX liposomes: experiment in vitro and in vivo | |
| Li et al. | Temperature-and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors | |
| Huang et al. | Development of a resveratrol–zein–dopamine–lecithin delivery system with enhanced stability and mucus permeation | |
| Arya et al. | Poly (d, l-lactide-co-glycolide)–chitosan composite particles for the treatment of lung cancer | |
| Naghizadeh et al. | Controlled release of fluorouracil (5-FU) from chitosan-co-poly (ethylene glycol)/poly (glycerol sebacate)-co-poly (ethylene glycol)-coated iron oxide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180817 |