CN114209658A - Preparation method of GSH (glutathione) response type paclitaxel fluorescent nanoparticles - Google Patents
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- CN114209658A CN114209658A CN202111491533.0A CN202111491533A CN114209658A CN 114209658 A CN114209658 A CN 114209658A CN 202111491533 A CN202111491533 A CN 202111491533A CN 114209658 A CN114209658 A CN 114209658A
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- 239000002105 nanoparticle Substances 0.000 title claims abstract description 40
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 title claims abstract description 34
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 229930012538 Paclitaxel Natural products 0.000 title claims abstract description 13
- 229960001592 paclitaxel Drugs 0.000 title claims abstract description 13
- 230000004044 response Effects 0.000 title claims abstract description 12
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 title description 30
- 229960003180 glutathione Drugs 0.000 title description 15
- 108010024636 Glutathione Proteins 0.000 title description 7
- 229940079593 drug Drugs 0.000 claims abstract description 34
- 239000003814 drug Substances 0.000 claims abstract description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000007850 fluorescent dye Substances 0.000 claims abstract description 21
- 229920001400 block copolymer Polymers 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 9
- 238000011068 loading method Methods 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000008367 deionised water Substances 0.000 claims abstract description 7
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 7
- 239000000463 material Substances 0.000 claims abstract description 6
- 238000005886 esterification reaction Methods 0.000 claims abstract description 3
- 239000006070 nanosuspension Substances 0.000 claims abstract 2
- 238000002347 injection Methods 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 238000007385 chemical modification Methods 0.000 abstract description 6
- 206010028980 Neoplasm Diseases 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 3
- 238000002059 diagnostic imaging Methods 0.000 abstract description 2
- 230000001105 regulatory effect Effects 0.000 abstract description 2
- 239000002245 particle Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 3
- 238000003384 imaging method Methods 0.000 description 3
- 239000002539 nanocarrier Substances 0.000 description 3
- 230000003321 amplification Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000001000 micrograph Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
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- 239000002904 solvent Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
- A61K49/0054—Macromolecular compounds, i.e. oligomers, polymers, dendrimers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0089—Particulate, powder, adsorbate, bead, sphere
- A61K49/0091—Microparticle, microcapsule, microbubble, microsphere, microbead, i.e. having a size or diameter higher or equal to 1 micrometer
- A61K49/0093—Nanoparticle, nanocapsule, nanobubble, nanosphere, nanobead, i.e. having a size or diameter smaller than 1 micrometer, e.g. polymeric nanoparticle
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
Abstract
The invention relates to a preparation method of GSH response type paclitaxel fluorescent nanoparticles, which comprises the following steps: preparing a taxol dimer drug connected by a disulfide bond as a hydrophobic drug through esterification reaction; dissolving the block copolymer and hydrophobic drugs or fluorescent dyes in tetrahydrofuran to be used as No. 1 stream; deionized water was used as stream No. 2. Injecting the No. 1 stream and the No. 2 stream into a two-channel restricted-area opposite-impact mixer for rapid mixing, collecting the prepared nano suspension, and adjusting the drug loading rate and the size of nano particles by adjusting the material ratio and the flow rate. The invention directly prepares the taxol dimer drug with GSH response and the fluorescent dye under the condition of no need of chemical modification to obtain the drug-loaded fluorescent nanoparticles, overcomes the complex chemical modification process, and realizes effective regulation and control of size and release performance by regulating the parameters of the preparation process. The invention has potential application prospect and value in the aspects of medical imaging and tumor treatment.
Description
Technical Field
The invention relates to a paclitaxel fluorescent nanoparticle with GSH (glutathione) response release, in particular to a high-drug-loading-capacity response release nanoparticle by a nano instantaneous precipitation method, belonging to the technical field of new materials.
Background
In recent years, nano-drugs using nanoparticles as carriers have attracted extensive attention and research in tumor imaging and therapy.
Paclitaxel is used as a natural drug with good anti-tumor activity, and is applied to chemotherapy for clinical tumor treatment. However, paclitaxel has poor water solubility and is difficult to disperse uniformly in an aqueous environment, and thus needs to be formulated into a suitable pharmaceutical dosage form. In the current commercial paclitaxel preparation used in clinic, in order to improve the dispersion effect in the water phase, a large amount of auxiliary agents are required to be added, thereby reducing the loading efficiency of paclitaxel drugs. Therefore, improving the loading of paclitaxel and the stability of its nano-formulation is one of the key problems in extensive research at present.
Whether the nanoparticles can be taken up by cells after entering the body or not and effectively release the loaded drug is another important characteristic of the drug-loaded nanoparticles. In order to effectively observe the transportation and enrichment conditions of the nanoparticles, a fluorescent group is usually required to be modified on the surface of a drug or a nano carrier, so that the nanoparticles emit fluorescence under laser irradiation, and the enrichment conditions of the nanoparticles are observed; in order to release the drug under the specific condition of the nanoparticle, a responsive group is usually modified on the surface of the drug or the nanocarrier, and the drug is released in a free form by the reaction of the responsive group under the stimulation of the specific condition at the tumor site. Therefore, the functional modification of the drug or the nano-carrier can apply the nano-drug in the fields of imaging, treatment and the like.
The existing preparation methods of the drug-loaded nanoparticles usually comprise a solvent volatilization method, a dialysis method and the like, and the preparation methods of the drug-loaded nanoparticles need longer preparation time, so that the defects of low drug loading rate, wide particle size distribution and the like exist. Aiming at the problems, the invention adopts a novel nano particle preparation method, and directly prepares the taxol dimer drug with GSH response and the fluorescent dye under the condition of no need of chemical modification to obtain the drug-loaded fluorescent nano particle, thereby overcoming the complicated chemical modification process and realizing the effective regulation and control of the size and the release performance by regulating the parameters of the preparation process. The method is simple to operate, easy to control, free of industrial amplification effect and potentially high in application value in the fields of medical imaging and tumor treatment.
Disclosure of Invention
In view of the above problems, the present invention is directed to preparing paclitaxel nanoparticles with stable and high loading capacity and responsive release property, which shortens the preparation time to several seconds by Flash Nanoprecipitation (FNP), realizes the regulation of the size of nanoparticles by adjusting the feeding amount and the flow rate of a stream, and can load fluorescent dye molecules into the nanoparticles together without chemical modification. The method has the advantages of simple operation, short process time, adjustable parameters, easy industrial amplification and the like, and has potential application value and industrial application prospect in the fields of medical tracing imaging, drug release and the like. The specific technical scheme is as follows:
a preparation method of GSH response type paclitaxel fluorescence nanoparticles is a method for preparing GSH response type paclitaxel dimer fluorescence nanoparticles by using a transient nano precipitation method, and comprises the following steps:
the taxol dimer drug linked by disulfide bonds is obtained as a hydrophobic drug by esterification reaction in advance. Dissolving the block copolymer and hydrophobic drugs or fluorescent dyes in tetrahydrofuran to be used as No. 1 stream; deionized water was used as stream No. 2. Injecting the No. 1 stream and the No. 2 stream into a two-channel restricted-area opposite-impact mixer through an injection pump simultaneously for rapid mixing, collecting the prepared nanometer suspension, and adjusting the drug loading rate and the size of the nanometer particles by adjusting the material proportion and the flow rate.
Further, the block copolymer is PLGA-b-PEG, the molecular weight of the PLGA block is 10kDa, the molecular weight of the PEG block is 5kDa, and the total molecular weight is 15 kDa.
Further, the concentration range of the block copolymer PLGA-b-PEG is 0-10 mg/mL.
Further, the configuration concentration of the block copolymer PLGA-b-PEG is 2 mg/mL.
Further, the hydrophobic drug or the fluorescent dye is a paclitaxel dimer or a fluorescent dye tetraphenyl ethylene methoxy derivative.
Further, the configuration concentrations of the hydrophobic drug or the fluorescent dye are respectively as follows: the preparation concentration of the taxol dimer is 10 mg/mL; the fluorescent dye tetraphenylethylene methoxyl derivative is prepared at the concentration of 0.2 mg/mL.
Further, the material ratio is adjusted by adjusting the concentration ratio of the block copolymer to the paclitaxel dimer in the tetrahydrofuran solution.
Further, the flow rate is adjusted by adjusting the injection flow rate of an injection pump connected with the flow stream to be 2-50 mL/min.
And further, the No. 1 stream and the No. 2 stream are simultaneously injected into the mixing cavity of the two-channel limited-area opposite-impact mixer through injection pumps.
The invention has the innovation point that a novel preparation method is adopted, the defect that a complex chemical modification is needed for connecting a fluorescent group is overcome, and the taxol fluorescent nanoparticles with response release performance are directly prepared.
Drawings
FIG. 1 is a scanning electron microscope image of nanoparticles with a 50 wt% charge ratio in example 1;
FIG. 2 is a scanning electron microscope image of nanoparticles with a charge ratio of 83 wt% in example 2;
FIG. 3 is a graph showing the particle size Distribution (DLS) of nanoparticles of examples 1 to 3 with different charge ratios;
FIG. 4 is a stability study of nanoparticles of examples 1-3 with different charge ratios;
FIG. 5 is a graph of the change in particle size after incubation with Glutathione (GSH) for a specified time in example 2;
FIG. 6 is a graph of the change in fluorescence of particles after incubation with Glutathione (GSH) for a specified time in example 2;
FIG. 7 is a graph of the change in size of nanoparticles prepared at different flow rates in example 4;
FIG. 8 is a stability study of the nanoparticle sizes prepared at different flow rates in example 4.
Detailed Description
The present invention will be further described with reference to the following examples, but the scope of the present invention is not limited to these examples. Other variations and modifications which may occur to those skilled in the art without departing from the spirit and scope of the invention are intended to be included within the scope of the invention.
Example 1
Taking 15mg of paclitaxel dimer and 15mg of block copolymer PLGA-b-PEG to dissolve in 1.5mL of tetrahydrofuran to serve as a stream 1, wherein the concentration is 10 mg/mL; 1.5mL of deionized water was taken as stream 2. Streams 1, 2 were loaded into gas-tight syringes respectively and the syringes were loaded into injection pumps, setting the injection flow rate to 50mL/min, while streams 1 and 2 were injected into a two-channel confined impingement mixer for mixing, the outlet stream below the mixer was further diluted with a beaker containing 27mL to a final concentration of 0.5 mg/mL. Removing the organic solvent to obtain the nano particles with the feeding ratio of 50 wt%.
Example 2
Taking 15mg of paclitaxel dimer, 0.1mg of fluorescent dye tetraphenyl ethylene methoxyl derivative and 3mg of block copolymer PLGA-b-PEG dissolved in 1.5mL of tetrahydrofuran as stream 1, wherein the concentrations are respectively 10mg/mL of paclitaxel dimer, 0.067mg/mL of fluorescent dye and 2mg/mL of block copolymer; 1.5mL of deionized water was taken as stream 2. And respectively loading the streams 1 and 2 into airtight injectors, loading the injectors to an injection pump, setting the injection flow rate to be 50mL/min, simultaneously injecting the stream 1 and the stream 2 into a two-channel restricted-area opposite impact mixer for mixing, and further diluting the outlet liquid flow below the mixer by using a beaker containing 27mL so as to obtain final concentrations of 0.5mg/mL of paclitaxel dimer, 0.0033mg/mL of fluorescent dye and 0.05mg/mL of block copolymer. Removing the organic solvent to obtain the nano particles with the feeding ratio of 83wt percent. And adding 100 times of equivalent glutathione into the obtained nanoparticles to verify the redox response performance, incubating the nanoparticles and the glutathione at 37 ℃, and testing the size distribution and the fluorescence intensity of the nanoparticles at a specific time point.
Example 3
Taking 15mg of paclitaxel dimer, 0.1mg of fluorescent dye tetraphenyl ethylene methoxyl derivative, and dissolving 1.5mL of tetrahydrofuran in block copolymer PLGA-b-PEG 3 or 7.5mg, wherein the concentrations of the tetrahydrofuran and the tetrahydrofuran are respectively 10mg/mL of paclitaxel dimer, 0.067mg/mL of fluorescent dye and 1 mg/mL or 5mg/mL of block copolymer as stream 1; 1.5mL of deionized water was taken as stream 2. Streams 1 and 2 were loaded into airtight syringes respectively and the syringes were loaded into injection pumps, the injection flow rate was set to 50mL/min, while stream 1 and stream 2 were injected into a two-channel confined impingement mixer for mixing, the outlet stream below the mixer was further diluted with a beaker containing 27mL, to final concentrations of 0.5mg/mL paclitaxel dimer, 0.0033mg/mL fluorescent dye, 0.1 or 0.25mg/mL block copolymer respectively. Removing the organic solvent to obtain the nano particles with a feeding ratio of 91 or 67 wt%.
Example 4
Taking 15mg of paclitaxel dimer, 0.1mg of fluorescent dye tetraphenyl ethylene methoxyl derivative and 3mg of block copolymer PLGA-b-PEG dissolved in 1.5mL of tetrahydrofuran as stream 1, wherein the concentrations are respectively 10mg/mL of paclitaxel dimer, 0.067mg/mL of fluorescent dye and 2mg/mL of block copolymer; 1.5mL of deionized water was taken as stream 2. Streams 1, 2 were loaded into airtight syringes respectively and the syringes were loaded into syringe pumps at which concentration the injection flow rates were set to 2, 5, 10, 15, 20, 35mL/min respectively while stream 1 and stream 2 were injected into a two-channel zone-limited impingement mixer at different flow rates for mixing, with the outlet stream below the mixer being further diluted with a beaker containing 27mL to a final concentration of 0.5mg/mL paclitaxel dimer, 0.0033mg/mL fluorochrome and 0.05mg/mL block copolymer. The method can realize effective regulation and control of the nano particles by removing the organic solvent to obtain the nano particles with different sizes and feeding ratios of 83 weight percent.
Claims (9)
1. A preparation method of GSH response type paclitaxel fluorescent nanoparticles is characterized by comprising the following steps:
preparing a taxol dimer drug connected by a disulfide bond as a hydrophobic drug through esterification reaction; dissolving the block copolymer and hydrophobic drugs or fluorescent dyes in tetrahydrofuran to be used as No. 1 stream; deionized water was used as stream No. 2. Injecting the No. 1 stream and the No. 2 stream into a two-channel restricted-area opposite-impact mixer for rapid mixing, collecting the prepared nano suspension, and adjusting the drug loading rate and the size of nano particles by adjusting the material ratio and the flow rate.
2. The method of claim 1, wherein the block copolymer is PLGA-b-PEG, the PLGA block has a molecular weight of 10kDa, the PEG block has a molecular weight of 5kDa, and the total molecular weight is 15 kDa.
3. The method of claim 2, wherein the block copolymer PLGA-b-PEG is configured at a concentration of less than 10 mg/mL.
4. The method of claim 3, wherein the PLGA-b-PEG is formulated at a concentration of 2 mg/mL.
5. The method of claim 1, wherein the fluorescent dye is a tetraphenylethylenemethoxy derivative.
6. The method according to claim 5, wherein the hydrophobic drug or the fluorescent dye is provided at a concentration of: the preparation concentration of the taxol dimer is 10 mg/mL; the fluorescent dye tetraphenylethylene methoxyl derivative is prepared at the concentration of 0.2 mg/mL.
7. The method of claim 1, wherein the adjusting the material ratio is performed by adjusting the concentration ratio of the block copolymer to the paclitaxel dimer in the tetrahydrofuran solution.
8. The method of claim 1, wherein the adjusting the flow rate is performed by adjusting an injection flow rate of an injection pump connecting the streams to 2-50 mL/min.
9. The method of claim 1, wherein the two streams # 1 and # 2 are injected simultaneously into the two-channel confined opposed mixer mixing chamber by a syringe pump.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114983976A (en) * | 2022-06-23 | 2022-09-02 | 浙江工业大学 | Taxol nano preparation and preparation method and application thereof |
| CN114989459A (en) * | 2022-06-01 | 2022-09-02 | 大连理工大学 | Preparation method of polymer fluorescent nanoparticles |
| CN114989459B (en) * | 2022-06-01 | 2024-04-26 | 大连理工大学 | Preparation method of polymer fluorescent nanoparticle |
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2021
- 2021-12-08 CN CN202111491533.0A patent/CN114209658A/en active Pending
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Non-Patent Citations (1)
| Title |
|---|
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114989459A (en) * | 2022-06-01 | 2022-09-02 | 大连理工大学 | Preparation method of polymer fluorescent nanoparticles |
| CN114989459B (en) * | 2022-06-01 | 2024-04-26 | 大连理工大学 | Preparation method of polymer fluorescent nanoparticle |
| CN114983976A (en) * | 2022-06-23 | 2022-09-02 | 浙江工业大学 | Taxol nano preparation and preparation method and application thereof |
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Application publication date: 20220322 |