CN105241793B - A kind of assay method of carrier micelle form particle diameter - Google Patents
A kind of assay method of carrier micelle form particle diameter Download PDFInfo
- Publication number
- CN105241793B CN105241793B CN201510564672.XA CN201510564672A CN105241793B CN 105241793 B CN105241793 B CN 105241793B CN 201510564672 A CN201510564672 A CN 201510564672A CN 105241793 B CN105241793 B CN 105241793B
- Authority
- CN
- China
- Prior art keywords
- gradient
- carrier micelle
- particle diameter
- micelle
- density
- 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.)
- Expired - Fee Related
Links
- 239000000693 micelle Substances 0.000 title claims abstract description 75
- 239000002245 particle Substances 0.000 title claims abstract description 36
- 238000003556 assay Methods 0.000 title claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 25
- 239000002105 nanoparticle Substances 0.000 claims abstract description 23
- 238000003921 particle size analysis Methods 0.000 claims abstract description 23
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 12
- 229940079593 drug Drugs 0.000 claims abstract description 11
- 229920001184 polypeptide Polymers 0.000 claims abstract description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 6
- 230000006641 stabilisation Effects 0.000 claims abstract description 5
- 238000011105 stabilization Methods 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 27
- 238000005119 centrifugation Methods 0.000 claims description 5
- 238000012360 testing method Methods 0.000 abstract description 11
- 238000000432 density-gradient centrifugation Methods 0.000 abstract description 2
- 239000007788 liquid Substances 0.000 abstract description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 18
- 238000005253 cladding Methods 0.000 description 11
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 description 7
- 229930195573 Amycin Natural products 0.000 description 7
- 230000008569 process Effects 0.000 description 6
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 5
- 229960002390 flurbiprofen Drugs 0.000 description 5
- 229960000779 irinotecan hydrochloride Drugs 0.000 description 5
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 5
- 238000004062 sedimentation Methods 0.000 description 4
- -1 ETHANOLAMINE-Polyethylene Chemical group 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000005352 clarification Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000013102 re-test Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003725 endotheliocyte Anatomy 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000000703 high-speed centrifugation Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The present invention relates to the assay method of a kind of carrier micelle form particle diameter, described method comprises the steps: that (1) prepares cesium chloride gradient solution, and the average density of described cesium chloride gradient solution is ρp；Low-density extension dish to CPS disk centrifuge formula nano-particle size analysis instrument is implanted sequentially cesium chloride gradient solution by high concentration to low concentration, sets up gradient；(2) after gradient solution gradient stabilization, by polypeptide drug-loaded micelle solution to be measured from low-density extension plate edge loading to CPS centrifugal particle size analyzer, the rate of settling of carrier micelle to be measured is measured, it is thus achieved that the form particle diameter of carrier micelle.The present invention uses the form particle diameter of density－gradient centrifuga－tion method test carrier micelle, by changing rotating speed and gradient liquid concentration, overcomes the shortcoming that carrier micelle density is little, accurately tests out the form particle diameter of carrier micelle.
Description
Technical field
The invention belongs to carrier micelle somatometry of physique field, relate to the assay method of a kind of carrier micelle form particle diameter, particularly relate to the assay method of the carrier micelle form particle diameter that a kind of CPS of utilization disk centrifuge formula nano-particle size analysis instrument is carried out.
Background technology
Polymer micelle is the pharmaceutical carrier in nanometer range, compared with the pharmaceutical carrier such as liposome, Nano microsphere, having the advantage that 1. macromole micelle has good biocompatibility, micelle can be effectively isolated medicine and external agency, weakens the impact on human body of the side effect bigger medicine；2. owing to there being the protection of hydrophilic segment outside macromole micelle, it is difficult to adsorb with protein and phagocyte and identify, it is ensured that its time of staying in blood plasma and tissue, circulation time in vivo is long, good stability；3. macromole micelle has passive targeting, and surface has active targeting after modifying targeting group；4. particle diameter is little, and stenosis area can be enriched with infiltration；5. being easy to preparation, it is convenient to preserve.
The size of micelle particle affects its circulation time in vivo, the distribution in organ-tissue, mechanism and cellular uptake kinetics of entering cell etc..Such as, it is smaller in size than that the micelle example of 200nm is more difficult to be understood by RES system, and can pass through blood capillary less than 5 μm, particle diameter polymer micelle between 10～100nm is obtained in that sufficiently long circulation time, and the micelle less than 200nm can pass through the filtration of endotheliocyte in spleen.Therefore, the mensuration for the particle diameter of carrier micelle form has very important significance.
CPS disk centrifuge formula nano-particle size analysis instrument is disk centrifuge formula nano-particle size analysis instrument, uses differential centrifugation sedimentation and carries out measurement and the analysis of grain graininess.Gradient solution set up in the centrifugal turntable of high speed rotating by CPS disk centrifuge formula nano-particle size analysis instrument, injects testing sample afterwards, measures the sedimentation velocity of sample, measures the particle diameter of sample according to Si Duokesi law (Stokes Law).
But, when utilizing CPS disk centrifuge formula nano-particle size analysis instrument to measure particle diameter, it is desirable to testing sample is more than gradient solution density, and has bigger density contrast, and such guarantee settles smoothly, determines sedimentation velocity.And for carrier micelle form, density is typically small, use conventional CPS disk centrifuge formula nano-particle size analysis instrument cannot obtain its size.
This area needs to develop a kind of method that can quickly measure carrier micelle form granularity.
Summary of the invention
For the deficiencies in the prior art, an object of the present invention is to provide the assay method of a kind of carrier micelle form particle diameter, and described method uses conventional CPS disk centrifuge formula nano-particle size analysis instrument, i.e. can read carrier micelle form particle diameter.
The present invention realizes especially by following technical scheme:
The assay method of a kind of carrier micelle form particle diameter comprises the steps:
(1) preparation cesium chloride gradient solution, the average density of described cesium chloride gradient solution is ρp；Low-density extension dish to CPS disk centrifuge formula nano-particle size analysis instrument is implanted sequentially cesium chloride gradient solution by high concentration to low concentration, sets up gradient；
(2) after gradient solution gradient stabilization, by polypeptide drug-loaded micelle solution to be measured from low-density extension plate edge loading to CPS centrifugal particle size analyzer, the rate of settling of carrier micelle to be measured is measured, it is thus achieved that the form particle diameter of carrier micelle；
Wherein, the least density of described cesium chloride gradient solution is more than carrier micelle density.
The present invention is by changing the loading position of carrier micelle, it is thus achieved that carrier micelle sedimentation velocity in gradient solution, and then obtains the form particle diameter of carrier micelle.
The average density of cesium chloride gradient solution of the present invention is 1.1～1.5g/mL, such as 1.2g/mL, 1.3g/mL, 1.4g/mL etc., preferably 1.25g/mL.Average density is too big, can reduce the resolution of test particle diameter；If average density is the least, then the testing time can be oversize.
The gradient number of cesium chloride gradient solution of the present invention is 7～11, such as 8,9,10, preferably 9.
The density of carrier micelle to be measured of the present invention is ρs, ρp-ρs≥0.1g/mL.The density contrast of more than 0.1g/mL, during high speed centrifugation, it is possible to effectively realize the mensuration of the movement locus of carrier micelle.
The concentration of polypeptide drug-loaded micelle solution to be measured of the present invention is 1.25～100mg/mL, such as 1.5mg/mL, 8mg/mL, 25mg/mL, 40mg/mL, 530mg/mL, 60mg/mL, 70mg/mL, 85mg/mL, 90mg/mL etc..
Rotating speed >=20000 turn/the min, such as 25000 turns/min of CPS disk centrifuge formula nano-particle size analysis instrument of the present invention, 28000 turns/min, 30000 turns/min, 33000 turns/min etc..Rotating speed is the least, for the micelle of test small particle, can be greatly increased the testing time.
Centrifugation time >=the 30min of CPS disk centrifuge formula nano-particle size analysis instrument of the present invention, such as 35min, 42min, 50min, 65min etc..Described centrifugation time increases according to the difference of carrier micelle density to be measured and gradient solution average density and shortens, additionally, strengthen centrifugal rotational speed, can shorten the testing time.
Step of the present invention (2) described applied sample amount is 90～110 μ L, such as 93 μ L, 96 μ L, 99 μ L, 103 μ L, 108 μ L etc., preferably 100 μ L.
As optimal technical scheme, the assay method of a kind of carrier micelle form particle diameter of the present invention comprises the steps:
(1) preparation cesium chloride gradient solution, the average density of described cesium chloride gradient solution is ρpFor 1.25g/mL, described gradient is 9 layers；Low-density expansion dish to CPS disk centrifuge formula nano-particle size analysis instrument is implanted sequentially cesium chloride gradient solution by high concentration to low concentration, sets up gradient；
(2) after gradient solution gradient stabilization, by polypeptide drug-loaded micelle solution to be measured from low-density expansion plate edge loading to CPS disk centrifuge formula nano-particle size analysis instrument, applied sample amount is 100 μ L, measures the rate of settling of carrier micelle to be measured, it is thus achieved that the form particle diameter of carrier micelle；Rotating speed >=20000 turn/the min of described CPS disk centrifuge formula nano-particle size analysis instrument, the centrifugation time >=30min of described CPS disk centrifuge formula nano-particle size analysis instrument.
Compared with prior art, there is advantages that
The present invention uses the form particle diameter of density－gradient centrifuga－tion method test carrier micelle, by changing rotating speed and gradient liquid concentration, overcomes the shortcoming that carrier micelle density is little, accurately test out the form particle diameter of carrier micelle, Monitoring lower-cut is 5nm, and upper limit of detection is 70nm, and measurement deviation is 0.6 ± 0.01%.
Accompanying drawing explanation
Fig. 1 is the particle diameter of the DSPE-PEG carrier micelle that the embodiment of the present invention 1 provides；
Fig. 2 is the particle diameter of the DSPE-PEG carrier micelle that the embodiment of the present invention 2 provides；
Fig. 3 is the particle diameter of the DSPE-PEG carrier micelle that the embodiment of the present invention 3 provides.
Detailed description of the invention
For ease of understanding the present invention, it is as follows that the present invention enumerates embodiment.Those skilled in the art, it will be clearly understood that the only help of described embodiment understands the present invention, are not construed as the concrete restriction to the present invention.
Preparation example 1
The preparation of DSPE-PEG carrier micelle, comprises the steps:
First take DSPE-PEG (PHOSPHATIDYL ETHANOLAMINE-Polyethylene Glycol) reagent a certain amount of in aqueous phase and add a small amount of glucose as stabilizer, DSPE-PEG is made to form micelle, it is subsequently adding hydrophobic drug amycin, it is stirred continuously until solution clarification, i.e. forms the carrier micelle of cladding amycin medicine.
Preparation example 2
The preparation of DSPE-PEG carrier micelle, comprises the steps:
First take DSPE-PEG (PHOSPHATIDYL ETHANOLAMINE-Polyethylene Glycol) reagent a certain amount of in aqueous phase and add a small amount of glucose as stabilizer, DSPE-PEG is made to form micelle, it is subsequently adding medicine irinotecan hydrochloride, it is stirred continuously until solution clarification, i.e. forms the carrier micelle of cladding irinotecan hydrochloride medicines.
Preparation example 3
The preparation of DSPE-PEG carrier micelle, comprises the steps:
First take DSPE-PEG (PHOSPHATIDYL ETHANOLAMINE-Polyethylene Glycol) reagent a certain amount of in aqueous phase and add a small amount of glucose as stabilizer, DSPE-PEG is made to form micelle, it is subsequently adding drug Flurbiprofen, it is stirred continuously until solution clarification, i.e. forms the carrier micelle of cladding flurbiprofen medicine.
Embodiment 1
The assay method of the particle diameter of the DSPE-PEG medicine carrying amycin micelle that preparation example 1 provides comprises the steps:
(1) preparation cesium chloride gradient solution, the average density of described cesium chloride gradient solution is ρpFor 1.25g/mL, described gradient is 9 layers；Low-density expansion dish to CPS disk centrifuge formula nano-particle size analysis instrument is implanted sequentially cesium chloride gradient solution by high concentration to low concentration, sets up gradient；
(2) after gradient solution gradient stabilization, the polypeptide drug-loaded micelle solution of the cladding amycin medicine to be measured preparation example 1 prepared expands plate edge loading to CPS disk centrifuge formula nano-particle size analysis instrument from low-density, applied sample amount is 100 μ L, measure the rate of settling of carrier micelle to be measured, obtain the form particle diameter of carrier micelle, the carrier micelle mean diameter recording cladding amycin medicine is 15.68nm, retest deviation about 0.6%.Rotating speed >=20000 turn/the min of described CPS disk centrifuge formula nano-particle size analysis instrument, the centrifugation time >=30min of described CPS disk centrifuge formula nano-particle size analysis instrument.
Embodiment 2
The assay method of the particle diameter of the DSPE-PEG medicine carrying irinotecan hydrochloride micelle that preparation example 2 provides, replaces with " carrier micelle of the cladding irinotecan hydrochloride medicines to be measured of preparation example 2 preparation " with differing only in of embodiment 1 by " carrier micelle of the cladding amycin medicine to be measured of preparation example 1 preparation "；After measured, the carrier micelle mean diameter of the cladding irinotecan hydrochloride medicines of preparation example 2 preparation is 14.32nm, retest deviation about 0.6%.
Embodiment 3
The assay method of the particle diameter of the DSPE-PEG medicine carrying flurbiprofen micelle that preparation example 3 provides, replaces with " carrier micelle of the cladding flurbiprofen medicine to be measured of preparation example 3 preparation " with differing only in of embodiment 1 by " carrier micelle of the cladding amycin medicine to be measured of preparation example 1 preparation "；After measured, the carrier micelle mean diameter of the cladding flurbiprofen medicine to be measured of preparation example 3 preparation is 12.89nm, retest deviation about 0.6%.
Applicant states, the present invention illustrates detailed process equipment and the technological process of the present invention by above-described embodiment, but the invention is not limited in above-mentioned detailed process equipment and technological process, i.e. do not mean that the present invention has to rely on above-mentioned detailed process equipment and technological process could be implemented.Person of ordinary skill in the field is it will be clearly understood that any improvement in the present invention, and the equivalence of raw material each to product of the present invention is replaced and the interpolation of auxiliary element, concrete way choice etc., within the scope of all falling within protection scope of the present invention and disclosure.
Claims (1)
1. the assay method of a carrier micelle form particle diameter, it is characterised in that described method includes walking as follows
Rapid:
(1) preparation cesium chloride gradient solution, the average density of described cesium chloride gradient solution is ρpFor
1.25g/mL, described gradient is 9 layers；Expand to the low-density of CPS disk centrifuge formula nano-particle size analysis instrument
Dish is implanted sequentially cesium chloride gradient solution by high concentration to low concentration, sets up gradient；
(2) after gradient solution gradient stabilization, by polypeptide drug-loaded micelle solution to be measured from low-density expansion plate edge
Sample is to CPS disk centrifuge formula nano-particle size analysis instrument, and applied sample amount is 100 μ L, measures carrier micelle to be measured
The rate of settling, it is thus achieved that the form particle diameter of carrier micelle；Described CPS disk centrifuge formula nano-particle size analysis instrument
Rotating speed >=20000 turn/min, the centrifugation time >=30min of described CPS disk centrifuge formula nano-particle size analysis instrument.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510564672.XA CN105241793B (en) | 2015-09-07 | 2015-09-07 | A kind of assay method of carrier micelle form particle diameter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510564672.XA CN105241793B (en) | 2015-09-07 | 2015-09-07 | A kind of assay method of carrier micelle form particle diameter |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105241793A CN105241793A (en) | 2016-01-13 |
| CN105241793B true CN105241793B (en) | 2016-10-26 |
Family
ID=55039515
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510564672.XA Expired - Fee Related CN105241793B (en) | 2015-09-07 | 2015-09-07 | A kind of assay method of carrier micelle form particle diameter |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105241793B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106074376A (en) * | 2016-06-27 | 2016-11-09 | 江苏师范大学 | A kind of glucagon-like peptide 1 slow release nanometer formulation, preparation method and application |
| CN108444876B (en) * | 2018-03-09 | 2020-06-16 | 国家纳米科学中心 | Method for determining state of protein ligand adsorbed on surface of nanoparticle |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5518738A (en) * | 1995-02-09 | 1996-05-21 | Nanosystem L.L.C. | Nanoparticulate nsaid compositions |
| CN104083342A (en) * | 2004-12-31 | 2014-10-08 | 伊休蒂卡有限公司 | Nanoparticle composition and methods of synthesis thereof |
| EP2010149A1 (en) * | 2006-04-07 | 2009-01-07 | Novavax, Inc. | Nanostructured compositions having antibacterial, anti-fungal, anti-yeast, and/or anti-viral properties |
| CN101314041B (en) * | 2008-06-26 | 2010-09-29 | 浙江大学 | Medicine carrying system of polymer micelle and preparation method thereof |
| CN101396563B (en) * | 2008-11-06 | 2011-06-29 | 中国药科大学 | Chitose derivates using octreotide as target ligand and use thereof in medicament |
| CN102462656A (en) * | 2010-11-04 | 2012-05-23 | 天津德兰玮诚生物技术有限公司 | Macrolide immunosuppressant drug loaded nanomicelle and preparation method thereof |
| TWI487754B (en) * | 2012-09-18 | 2015-06-11 | Rohm & Haas | Aqueous coating composition and coating formed therefrom having a particular gloss profile |
-
2015
- 2015-09-07 CN CN201510564672.XA patent/CN105241793B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN105241793A (en) | 2016-01-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Maas et al. | Possibilities and limitations of current technologies for quantification of biological extracellular vesicles and synthetic mimics | |
| Nunes et al. | 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs | |
| Aryal et al. | Erythrocyte membrane-cloaked polymeric nanoparticles for controlled drug loading and release | |
| Tong et al. | Self-assembly of phospholipid–PEG coating on nanoparticles through dual solvent exchange | |
| Rampersaud et al. | The effect of cage shape on nanoparticle-based drug carriers: anticancer drug release and efficacy via receptor blockade using dextran-coated iron oxide nanocages | |
| Varenne et al. | Evaluation of zeta potential of nanomaterials by electrophoretic light scattering: Fast field reversal versus Slow field reversal modes | |
| CN105241793B (en) | A kind of assay method of carrier micelle form particle diameter | |
| CN112716913B (en) | Bionic nano-drug for targeting local myocardial infarction and preparation method thereof | |
| Meng et al. | Negative CT contrast agents for the diagnosis of malignant osteosarcoma | |
| Mair et al. | Single particle tracking reveals biphasic transport during nanorod magnetophoresis through extracellular matrix | |
| Digiacomo et al. | Effect of molecular crowding on the biological identity of liposomes: an overlooked factor at the bio-nano interface | |
| Clogston et al. | Importance of physicochemical characterization prior to immunological studies | |
| CN110279672B (en) | Double-drug-loading erythrocyte carrier, preparation method and application thereof | |
| CN111249255A (en) | Novel microsphere composite preparation for carrying drug by temperature-sensitive hydrogel and preparation method thereof | |
| CN216824184U (en) | Local bionic structure of target myocardial infarction | |
| Lovegrove et al. | The flow of anisotropic nanoparticles in solution and in blood | |
| Hristov et al. | Impact of dynamic sub-populations within grafted chains on the protein binding and colloidal stability of PEGylated nanoparticles | |
| Wang et al. | Isolation and usage of exosomes in central nervous system diseases | |
| CN112704743A (en) | Sea cucumber saponin mesoporous silica nanocomposite for injection and preparation method and application thereof | |
| Lai et al. | Amphiphilic polymer coated nanodiamonds: A promising platform to deliver azonafide | |
| KR101717010B1 (en) | Nanoparticle sensitive to bioenvironment comprising poly(amino acid) for early diagnosis or treatment of cancers | |
| Macher et al. | Bottom-Up Assembly of Bioinspired, Fully Synthetic Extracellular Vesicles | |
| Durak-Kozica et al. | Comparison of qNANO results from the isolation of extracellular microvesicles with the theoretical model | |
| CN108371653A (en) | A kind of nano-micelle and its application | |
| CN101015549A (en) | Preparing and detecting method of triptolide liposome nano granule |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20161026 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |