CN107669639A - A kind of method for preparing charge reversal type nano particle using instantaneous nanometer sedimentation - Google Patents
A kind of method for preparing charge reversal type nano particle using instantaneous nanometer sedimentation Download PDFInfo
- Publication number
- CN107669639A CN107669639A CN201710914503.3A CN201710914503A CN107669639A CN 107669639 A CN107669639 A CN 107669639A CN 201710914503 A CN201710914503 A CN 201710914503A CN 107669639 A CN107669639 A CN 107669639A
- Authority
- CN
- China
- Prior art keywords
- liquid
- liquid streams
- liquid stream
- nano particle
- flow velocity
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a kind of preparation method that charge reversal type nano particle is prepared using instantaneous nanometer sedimentation, including step：Block copolymer DexbPLGA is dissolved in deionized water, as No. 1 liquid stream；Bata-carotene and PDMAEMAbPCL is dissolved in tetrahydrofuran, as No. 2 liquid streams；No. 3 liquid streams and No. 4 liquid streams are deionized water.It will quickly be mixed in four bursts of liquid streams simultaneously injecting mixer by two syringe pumps, collect the nano suspending liquid of formation.The size of nano particle is can adjust by the velocity ratio adjusted between No. 1 liquid stream and No. 2 liquid streams and No. 3 liquid streams and No. 4 liquid streams.Organic solvent is removed eventually through dialysis.The present invention have the advantages that it is quick, can industry amplify, being imaged to diagnose etc. in nano-antibacterial, oncotherapy has wide application value.
Description
Technical field
The present invention relates to a kind of charge reversal type nano particle of pH responses, is prepared specifically by instantaneous nanometer sedimentation
Charge reversal nano particle, belongs to new material technology field.
Background technology
In recent years, nano particle has become biology, material, doctor as the research of anti-biotic material or antineoplastic drug carrier
Worker's focus of attention.Nano material antibacterial carries a key of medicine treatment and is how in different environments such as
PH, stable nano material under ion concentration.And the distribution of nano-material surface electric charge greatly have impact on the stabilization of nanoparticle
Property, so as to determine effective antibacterial of nano particle or loading functional.
The surface nature of nano particle also contributes to the final antibacterial or carrier medicine carrying efficiency of drug-loading nanoparticles.For example, nanometer
The surface charge of particle is just or excessively negative, and nano particle can be removed quickly in body fluid circulatory by RES systems.Research shows to receive
The surface charge of rice grain is neutral or slightly negative（<-15 mV）With macrocyclic property.However, when drug-loading nanoparticles are enriched with
During to bacterium or tumor section, because cell membrane surface current potential is negative, therefore surface charge is that positive nano particle can pass through
Electrostatic interaction promotes the phagocytosis of bacterium or tumour cell to nano particle, and this needs nanoparticle surface charge for just again.
The demand of this contradiction is just promoting research of the people to charge reversal type nano particle.Method prepared by current nano particle is main
It is divided into emulsion-solvent evaporation method, spray drying, dialysis etc..But these methods for preparing nano particle have its limitation.
The content of the invention
Research shows that the microenvironment of tumour cell is relatively low compared to the pH of normal fluid environment, about 6.5 ~ 6.8.Utilize
This characteristic, this characteristic can be realized by designing a series of pH response nanos material, so as to significantly improve medicament-carried nano
The anti-cancer effectiveness of grain.
Present invention employs a kind of novel nanometer grain preparation method, i.e., settled using rapid nano（Flash
Nanoprecipitation, FNP）Method, charge reversal type nano particle is quickly prepared, preparation time only has several seconds, together
When can by adjust velocity ratio regulate and control nano particle size, the preparation method have simple to operate, preparation time is extremely short, repeat
Property it is good, it is easy industry amplification the advantages that, there is great prospects for commercial application.Concrete scheme is：
A kind of preparation method that charge reversal type nano particle is prepared using instantaneous nanometer sedimentation, it is characterised in that including such as
Lower step：
Block copolymer Dex-b- PLGA is dissolved in deionized water, as No. 1 liquid stream；Beta carotene and PDMAEMA-b- PCL is molten
In tetrahydrofuran, as No. 2 liquid streams；No. 3 liquid streams and No. 4 liquid streams are deionized water.By two syringe pumps by four bursts of liquid streams
Quickly mixed in injecting mixer simultaneously, collect the nano suspending liquid of formation.By adjusting No. 1 liquid stream and No. 2 liquid streams and 3
Velocity ratio number between liquid stream and No. 4 liquid streams can adjust the size of nano particle.Organic solvent is removed eventually through dialysis.
The Dex-b- PLGA configuration concentrations are 1 mg/mL；
The PDMAEMA-b- PCL configuration concentrations are 0.5 mg/mL；
The beta carotene solution concentration is 0.5 mg/mL；
The injection flow velocity of No. 1 liquid stream is 12 mL/min；
The injection flow velocity of No. 2 liquid streams is 12 mL/min；
The injection flow velocity of No. 3 liquid streams is 12 ~ 108 mL/min；
The injection flow velocity of No. 4 liquid streams is 12 ~ 108 mL/min.
Further：Dex-b- PLGA concentration is 1 mg/mL, PDMAEMA-b- PCL configuration concentrations are 0.5 mg/mL；
Beta carotene solution concentration is 0.5 mg/mL；The flow velocity of No. 1 liquid stream and No. 2 liquid streams is fixed as 12 mL/min, No. 3 liquid streams and 4
The flow velocity of number liquid stream is adjusted to 36 ~ 108 mL/min by syringe pump, prepares the nano particle different in flow rate than under.
Further：Its used device is that four-way quickly liquidates vortex mixer, and four plume liquid phases are every 90 degree, together
When inject vortex centers, continuously quickly prepare nano-particle.
The innovative point of the present invention is to employ a kind of novel nanometer grain preparation method, and by being simply blended two
Kind block copolymer realizes the effect of charge reversal.The preparation method is simple and efficient and easily controllable, in the diagnoses and treatment of tumour
Field has broad application prospects.
Brief description of the drawings
Fig. 1 is to prepare charge reversal nano particle schematic diagram；
Fig. 2 is the DLS of charge reversal type nano particle prepared by embodiment 1；
Fig. 3 is the Zeta Potential of charge reversal type nano particle prepared by embodiment 1（Zeta potential）Become with pH changes
Gesture figure；
Fig. 4 is charge reversal type nano particle transmission electron microscope picture prepared by embodiment 1；
Fig. 5 is that the particle diameter different in flow rate than lower charge reversal type nano particle prepared by embodiment 1 ~ 4 compares.
Fig. 6 is the stability study of charge reversal type nano particle prepared by embodiment 1.
Embodiment
Below, present invention is further illustrated with embodiment, but protection scope of the present invention is not limited in implementing
Example.The others made to those skilled in the art in the case of without departing substantially from spirit and scope of the present invention change and repaiied
Change, be included within the scope of the present invention.
Embodiment 1
Dex-b- PLGA is dissolved in deionized water, and concentration is 1 mg/mL, as liquid stream 1；PDMAEMA-b- PCL and beta carotene
It is dissolved in tetrahydrofuran, concentration is all 0.5 mg/mL, as liquid stream 2；Liquid stream 3 and liquid stream 4 are deionized water, pH 3.Two
Syringe pump controls the flow velocity of liquid stream 1 and liquid stream 2 and liquid stream 3 and liquid stream 4 respectively, and the flow velocity of liquid stream 1 and liquid stream 2 is arranged to 12 mL/
The flow velocity of min, liquid stream 3 and liquid stream 4 is arranged to 36 mL/min, and four bursts of liquid streams are simultaneously into progress in four-way vortex mixer
Quick mixing, using the Sunk-fund effect of poor solvent, the nano granule suspension of preparation is collected, dialyses and removes organic solvent, i.e.,
It is 1 for velocity ratio:3 charge reversal type nano particle.Product is characterized, and accompanying drawing 2 is DLS granularmetric analyses, and accompanying drawing 4 is Zeta
For Potential with pH value of solution mutation analysis, accompanying drawing 3 is transmission electron microscope analysis.
Embodiment 2
Dex-b- PLGAL is dissolved in deionized water, and concentration is 1 mg/mL, as liquid stream 1；PDMAEMA-b- PCL and β-carrot
Element is dissolved in tetrahydrofuran, and concentration is all 0.5 mg/mL, as liquid stream 2；Liquid stream 3 and liquid stream 4 are deionized water, pH 3.Two
Platform syringe pump controls the flow velocity of liquid stream 1 and liquid stream 2 and liquid stream 3 and liquid stream 4 respectively, and the flow velocity of liquid stream 1 and liquid stream 2 is arranged to 12
The flow velocity of mL/min, liquid stream 3 and liquid stream 4 is arranged to 60 mL/min, and four bursts of liquid streams enter in four-way vortex mixer simultaneously
The quick mixing of row, using the Sunk-fund effect of poor solvent, the nano granule suspension of preparation is collected, dialyses and removes organic solvent,
As velocity ratio is 1:5 charge reversal type nano particle.
Embodiment 3
Dex-b- PLGAL is dissolved in deionized water, and concentration is 1 mg/mL, as liquid stream 1；PDMAEMA-b- PCL and β-carrot
Element is dissolved in tetrahydrofuran, and concentration is all 0.5 mg/mL, as liquid stream 2；Liquid stream 3 and liquid stream 4 are deionized water, pH 3.Two
Platform syringe pump controls the flow velocity of liquid stream 1 and liquid stream 2 and liquid stream 3 and liquid stream 4 respectively, and the flow velocity of liquid stream 1 and liquid stream 2 is arranged to 12
The flow velocity of mL/min, liquid stream 3 and liquid stream 4 is arranged to 84 mL/min, and four bursts of liquid streams enter in four-way vortex mixer simultaneously
The quick mixing of row, using the Sunk-fund effect of poor solvent, the nano granule suspension of preparation is collected, dialyses and removes organic solvent,
As velocity ratio is 1:7 charge reversal type nano particle.
Embodiment 4
Dex-b- PLGA is dissolved in deionized water, and concentration is 1 mg/mL, as liquid stream 1（Liquid stream 1, Dex-b-PLGA
It is dissolved in the deionized water of pH=3）；PDMAEMA-b- PCL and beta carotene are dissolved in tetrahydrofuran, and concentration is all 0.5
Mg/mL, as liquid stream 2；Liquid stream 3 and liquid stream 4 are deionized water, pH 3.Two syringe pumps control liquid stream 1 and liquid stream 2 respectively
（Liquid stream 2, PDMAEMA-b- PCL and beta carotene are dissolved in tetrahydrofuran）With the flow velocity of liquid stream 3 and liquid stream 4, liquid stream 1 and liquid
The flow velocity of stream 2 is arranged to 12 mL/min, liquid stream 3（The deionized water of pH=3）With liquid stream 4（The deionized water of pH=3）Flow velocity set
108 mL/min are set to, four bursts of liquid streams are quickly mixed into four-way vortex mixer is interior simultaneously, utilize poor solvent
Sunk-fund effect, the nano granule suspension of preparation is collected, dialysis removes organic solvent, and as velocity ratio is 1:9 charge reversal
Type nano particle.
Claims (3)
- A kind of 1. preparation method that charge reversal type nano particle is prepared using instantaneous nanometer sedimentation, it is characterised in that including Following steps：Block copolymer Dex-b- PLGA is dissolved in deionized water, as No. 1 liquid stream；Beta carotene and PDMAEMA-b- PCL is molten In tetrahydrofuran, as No. 2 liquid streams；No. 3 liquid streams and No. 4 liquid streams are deionized water；It will quickly be mixed in four bursts of liquid streams simultaneously injecting mixer by two syringe pumps, collect the nanoparticle suspension of formation Liquid；The chi of nano particle is can adjust by the velocity ratio adjusted between No. 1 liquid stream and No. 2 liquid streams and No. 3 liquid streams and No. 4 liquid streams It is very little；Organic solvent is removed eventually through dialysis；The Dex-b- PLGA configuration concentrations are 1 mg/mL；The PDMAEMA-b- PCL configuration concentrations are 0.5 mg/mL；The beta carotene solution concentration is 0.5 mg/mL；The injection flow velocity of No. 1 liquid stream is 12 mL/min；The injection flow velocity of No. 2 liquid streams is 12 mL/min；The injection flow velocity of No. 3 liquid streams is 12 ~ 108 mL/min；The injection flow velocity of No. 4 liquid streams is 12 ~ 108 mL/min.
- 2. preparation method according to claim 1, it is characterised in that Dex-b- PLGA concentration is 1 mg/mL, PDMAEMA-b- PCL configuration concentrations are 0.5 mg/mL；Beta carotene solution concentration is 0.5 mg/mL；No. 1 liquid stream and No. 2 liquid The flow velocity of stream is fixed as 12 mL/min, and the flow velocity of No. 3 liquid streams and No. 4 liquid streams is adjusted to 36 ~ 108 mL/ by syringe pump Min, prepare the nano particle different in flow rate than under.
- 3. preparation method according to claim 1, it is characterised in that its used device is that four-way quickly liquidates whirlpool Blender is flowed, four plume liquid phases inject vortex centers every 90 degree, continuously quickly prepare nano-particle.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710914503.3A CN107669639A (en) | 2017-09-30 | 2017-09-30 | A kind of method for preparing charge reversal type nano particle using instantaneous nanometer sedimentation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710914503.3A CN107669639A (en) | 2017-09-30 | 2017-09-30 | A kind of method for preparing charge reversal type nano particle using instantaneous nanometer sedimentation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107669639A true CN107669639A (en) | 2018-02-09 |
Family
ID=61138661
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710914503.3A Pending CN107669639A (en) | 2017-09-30 | 2017-09-30 | A kind of method for preparing charge reversal type nano particle using instantaneous nanometer sedimentation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107669639A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108542894A (en) * | 2018-02-14 | 2018-09-18 | 华东理工大学 | A method of preparing charge reversal type nano particle using instantaneous nanometer sedimentation |
| CN113185830A (en) * | 2021-04-29 | 2021-07-30 | 中山大学 | Polyurethane nano-particle with polycaprolactone and brominated copolymer thereof as soft segment and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009020865A1 (en) * | 2007-08-03 | 2009-02-12 | The Board Of Regents Of The University Of Nebraska | Surface-modified nanoparticles for intracellular delivery of therapeutic agents and composition for making same |
| CN106511298A (en) * | 2015-09-10 | 2017-03-22 | 中国科学院高能物理研究所 | Charge-transfer nanoparticles and preparation method thereof |
-
2017
- 2017-09-30 CN CN201710914503.3A patent/CN107669639A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009020865A1 (en) * | 2007-08-03 | 2009-02-12 | The Board Of Regents Of The University Of Nebraska | Surface-modified nanoparticles for intracellular delivery of therapeutic agents and composition for making same |
| CN106511298A (en) * | 2015-09-10 | 2017-03-22 | 中国科学院高能物理研究所 | Charge-transfer nanoparticles and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| ANJA CAR等: ""pH-Responsive PDMS‑b‑PDMAEMA Micelles for Intracellular Anticancer Drug Delivery"", 《BIOMACROMOLECULES》 * |
| MINGWEI WANG等: ""Biocompatible Nanoparticle Based on Dextran-b-Poly(L-lactide) Block Copolymer Formed by Flash Nanoprecipitation"", 《CHEMISTRY LETTERS》 * |
| YING LIU等: ""Ostwald Ripening of Carotene Nanoparticles"", 《PHYSICAL REVIEW LETTERS》 * |
| 姚加: ""嵌段共聚物PDMAEMA-b-PCL 的合成、修饰及其水溶液性质研究"", 《化学学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108542894A (en) * | 2018-02-14 | 2018-09-18 | 华东理工大学 | A method of preparing charge reversal type nano particle using instantaneous nanometer sedimentation |
| CN113185830A (en) * | 2021-04-29 | 2021-07-30 | 中山大学 | Polyurethane nano-particle with polycaprolactone and brominated copolymer thereof as soft segment and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Majedi et al. | Microfluidic assisted self-assembly of chitosan based nanoparticles as drug delivery agents | |
| CN108542894A (en) | A method of preparing charge reversal type nano particle using instantaneous nanometer sedimentation | |
| DE69931085T2 (en) | System and method for separating biological cells | |
| CN106038512B (en) | A kind of LBL self-assembly nano-carrier and preparation method thereof | |
| CN107669639A (en) | A kind of method for preparing charge reversal type nano particle using instantaneous nanometer sedimentation | |
| CN107714674A (en) | A kind of preparation method of PLGA microballoons | |
| CN103550776A (en) | Hydrophobic drug nanoparticles as well as preparation method and application thereof | |
| US20160158383A1 (en) | Method and device for manufacturing polymer particles containing a therapeutic material | |
| CN106177974A (en) | A kind of preparation carrying antigenic polymers lipid nanospheres and the application as vaccine adjuvant | |
| Farahani et al. | Microfluidic fabrication of berberine-loaded nanoparticles for cancer treatment applications | |
| CN114209658A (en) | Preparation method of GSH (glutathione) response type paclitaxel fluorescent nanoparticles | |
| CN103611172A (en) | Nanorealgar-carrying magnetic albumin nanospheres and preparation method thereof | |
| US20110182994A1 (en) | Methods and systems for production of nanoparticles | |
| CN108339125A (en) | It is a kind of efficiently, targeted medicament carrying nano micella and preparation method and application | |
| CN104549582B (en) | A kind of micro-fluidic chip and the application in prepared by dispersed nano particle thereof | |
| CN105126102A (en) | Hypocrellin B nanoparticle and preparation method thereof | |
| CN103520112A (en) | Preparation method for nanoparticles with small particle size and nanoparticle medicine carrier | |
| Hu et al. | Fabrication and surface characterization of electrosprayed poly (L‐lactide) microspheres | |
| CN108610460B (en) | Active oxygen stimulation response type nano gel drug carrier and preparation method and application thereof | |
| CN116077467A (en) | Microfluidic device and method for preparing composite biomembrane coated drug-loaded nano-particles | |
| CN110507631B (en) | Method for preparing albumin paclitaxel nanoparticles | |
| CN108451931B (en) | PAH/F polyelectrolyte compound nano-carrier and preparation method thereof | |
| CN109730976B (en) | Method for preparing albumin nanoparticles based on free radical oxidation | |
| CN106265513A (en) | A kind of effect of nano-paclitaxel and preparation method thereof | |
| CN105878185A (en) | Method for controlling mass parameters of nano-particles based on microfluidic technology |
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 | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20180209 |