CN106511297B - A kind of adriamycin nano particle of size tunable and preparation method thereof - Google Patents
A kind of adriamycin nano particle of size tunable and preparation method thereof Download PDFInfo
- Publication number
- CN106511297B CN106511297B CN201610819358.6A CN201610819358A CN106511297B CN 106511297 B CN106511297 B CN 106511297B CN 201610819358 A CN201610819358 A CN 201610819358A CN 106511297 B CN106511297 B CN 106511297B
- Authority
- CN
- China
- Prior art keywords
- adriamycin
- nano particle
- polyethylene glycol
- alt
- poly
- 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
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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Nanotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a kind of adriamycin nano particles of size tunable, it for kernel, is wrapped up the kernel by self assembly by polyethylene glycol-adriamycin beta-cyclodextrin modified with poly- (isobutene-alt- maleic anhydride) and is formed with Polyethylene glycol vitamin E succinate (TPGS).The present invention also provides the preparation methods of the adriamycin nano particle.Different from the nano particle of traditional formation by chemical bond and the method preparation of fracture, adriamycin nano grain diameter of the invention is controllable, preparation process is simple, reaction condition is mild, raw material is easily obtained, and has good biological safety and histocompatbility.
Description
Technical field
The present invention relates to the preparations of nano particle and biologic applications field, and in particular to a kind of adriamycin of size tunable is received
Rice grain and preparation method thereof.
Background technique
For a long time, researcher has been devoted to study a kind of organic polymer nanometer that can prepare size tunable
The method of particle.In the past few decades, numerous studies are made that in the biology of nano particle and the application aspect of pharmaceutical field,
And there are several different types of nano particles to obtain different field, different degrees of application.For example, the corresponding tool of modification
There are gold nano grain, the superparamagnetic nanoparticle of the molecule of targeting, can be used for showing interior tumor cell；Drug molecule is repaired
It adorns on nanoparticle, anti-tumor drug can be made in lesions position slow release by certain transporting mechanism, this can be big
The big side effect for reducing anticancer drug, while extending drug treating time, improve drugs against tumor effect；In addition, nano particle
Iconography is applied also for, for Real-time and Dynamic Detection such as MRI, PET etc..
However, the synthesis of nano particle still faces problems with using upper, for example, the size and form of nano particle
Not easy to control, biological safety is low and immunogenicity is strong, and human recycle system stablizes bad, and then is difficult smoothly to reach lesion,
The problems such as not degradable in vivo.
Summary of the invention
To overcome technological deficiency existing in the prior art, an object of the present invention be to provide a kind of size tunable Ah
Mycin nano particle.
It is a further object of the present invention to provide the preparation methods of the adriamycin nano particle.
The adriamycin nano particle of size tunable provided by the invention using Polyethylene glycol vitamin E succinate as kernel,
It is wrapped up in described by the modified beta-cyclodextrin of polyethylene glycol-adriamycin and poly- (isobutene-alt- maleic anhydride) by self assembly
Karyomorphism at.
Specifically, the adriamycin nano particle of size tunable of the invention includes outer layer, middle layer and kernel,
In, kernel is Polyethylene glycol vitamin E succinate (TPGS), and middle layer is that poly- (isobutene-alt- maleic anhydride) is modified
Beta-cyclodextrin (p (IB-alt-MAnh)-CD), plays function served as bridge in the assembling of nano particle, and adriamycin can be by super
Molecular action is embedded into the hydrophobic internal cavities of cyclodextrin, and the hydrophobic segment in poly- (isobutene-alt- maleic anhydride) then can be with
Interior nuclear interaction plays the role of connecting kernel and outer layer.Outer layer is then polyethylene glycol-adriamycin (mPEG-DOX), knot
Structure is as follows:
During host-guest molecular self-assembling, the hydrophobicity of cyclodextrin inner chamber and the benzene ring structure of adriamycin are utilized
Interaction, adriamycin end are embedded into the inner cavity of cyclodextrin, and the polyethylene glycol end for connecting adriamycin forms hydrophilic outer layer.
In adriamycin nano particle provided by the invention, polyethylene glycol tocopheryl succinate can be adjusted according to the requirement of partial size
The dosage of acid esters.In embodiments of the present invention, the quality of the Polyethylene glycol vitamin E succinate kernel is described poly-
0.05~20 times of the beta-cyclodextrin gross mass that ethylene glycol-adriamycin and poly- (isobutene-alt- maleic anhydride) are modified；Preferably
0.1~10 times；More preferably 0.2~5 times.
In adriamycin nano particle provided by the invention, kernel also may include other active components, especially can be with Ah mould
Element combination increases the anti-tumor drug of anti-tumor activity.In a preferred embodiment of the present invention, also contain in the kernel
There is paclitaxel nano crystal, taxol and adriamycin combination can produce synergistic function, thus can greatly improve nano particle
Anti-tumor activity, by adjust taxol the adjustable paclitaxel nano crystal of dosage size, and then also be adjusted receive
Rice grain particle size；Moreover, the structure of taxol can also preferably with the ethylene linkage end in poly- (isobutene-alt- maleic anhydride)
In conjunction with to form more stable nano particle.
In adriamycin nano particle provided by the invention, poly- (isobutene-alt- maleic anhydride) modified β-ring paste
Essence is poly- (isobutene-alt- maleic anhydride) and hexamethylene diamine-beta-cyclodextrin as obtained by coupling reaction.Its preparation process is in EDC/
It under NHS effect, can be carried out in DMSO equal solvent, the pH value for adjusting reaction system is 8.0~9.0, is stirred at room temperature 48~72
Hour, after reaction with phosphate buffer dialysis (pH8.0~9.0) 36~48 hours, after freeze-drying to obtain the final product, and in low
Temperature saves.
In adriamycin nano particle provided by the invention, the average molecular weight of poly- (isobutene-alt- maleic anhydride)
It can be 5000~10000.
In adriamycin nano particle provided by the invention, the polymerization degree n of polyethylene glycol can in the polyethylene glycol-adriamycin
Think 45~450, molecular weight can be 2000~20000.
Existing method can be used in the preparation of polyethylene glycol-adriamycin, can also be such as following procedure: by mPEG- hydrazides and Ah mould
Element is dissolved in anhydrous polar solvent, and excess of triethylamine is added, and room temperature is protected from light, and 48~72h of stirring makes its fully reacting, pure
Change.The molar ratio of mPEG- hydrazides and adriamycin can be 1:0.2~5, preferably 1:1.5~2.0.It can be used in reaction process
NaOH solution etc. adjusts the pH value of reaction system, keeps it in 8.0~10.0, preferably 8.5~9.0.
It also may include having one of surfactant, emulsifier or more in adriamycin nano particle provided by the invention
Kind, can partly or entirely substitute kernel is Polyethylene glycol vitamin E succinate (TPGS).For example, can be surfactant
IGEPAL CO-520, emulsifier PluronicF 127 etc..
The preparation method of adriamycin nano particle provided by the invention, comprising the following steps:
S1: the modified beta-cyclodextrin of polyethylene glycol-adriamycin and poly- (isobutene-alt- maleic anhydride) is soluble in water super
Self assembly is carried out under the conditions of sound, freeze-drying obtains supramolecular complex；
S2: Polyethylene glycol vitamin E succinate and optional paclitaxel nano crystal are dissolved in dehydrated alcohol and are made
Obtain emulsion；
S3: the resulting supramolecular complex of step S1 is soluble in water, then emulsion obtained by step S2 is added thereto,
Dehydrated alcohol is volatilized, is centrifuged after 0.45 μm of membrane filtration up to the adriamycin nano particle.
In above-mentioned preparation method, in the resulting emulsion of step S2, Polyethylene glycol vitamin E succinate and optional
Paclitaxel nano Crystallization nano-micelle form.
In above-mentioned preparation method, the polyethylene glycol-adriamycin is modified with poly- (isobutene-alt- maleic anhydride)
The mass ratio of beta-cyclodextrin is 1:50~60.
In above-mentioned preparation method, in the step S1, by polyethylene glycol-adriamycin and poly- (isobutene-alt- maleic acid
Acid anhydride) modified beta-cyclodextrin is soluble in water, and adjusting pH value is 8.0~9.0, carries out self assembly.
The host-guest between p (IB-alt-MAnh) and mPEG-DOX is utilized certainly in adriamycin nano particle provided by the invention
Group reaction cartridge forms nano particle, and hydrazone bond has acid-sensitive in mPEG-DOX molecule, and under acidic environment, mPEG-DOX is released
Doxorubicin molecules, and under organism physiological environment (pH7.35~7.45), mPEG-DOX will not be hydrolyzed, and will not discharge Ah
Mycin molecule.On the other hand, adriamycin nano particle provided by the invention joined the molecule TPGS with surface-active, together
When wrap up hydrophobic antitumor drug paclitaxel (PTX), adjust taxol dosage be adjusted nano particle size.TPGS with
PTX forms hydrophobic inner core, facilitates hydrophobic drug taxol in the intracorporal transport of machine, the smaller nano particle of size is more easy to
Into inside tumor tissues.After adriamycin nano particle provided by the invention reaches in tumor tissues, mPEG-DOX occurs to divide
Solution, DOX, PTX are released, the two drug combination, are had synergistic effect, can be significantly improved anti-tumor activity, the targeting of drug
Property is stronger, and therapeutic effect greatly enhances.
Different from the nano particle of traditional formation by chemical bond and the method preparation of fracture, nanometer of the invention
Grain preparation process is simple, and reaction condition is mild, and raw material is easily obtained, and assembles final resulting nano particle using ultrasonic power,
Granular size is also adjusted by changing ultrasound condition.Nano particle of the invention has good biological safety and tissue phase
Capacitive prepares nano particle using the host-guest self-assembling reaction between supermolecule, can modify the anti-of adriamycin even multiple combinations
Cancer drug greatly enhances curative effect of medication to play the synergistic effect of anti-tumor drug.In addition, nano particle prepared by the present invention
With acid-sensitive, the release of drug is more conducive in the acidic environment of tumor tissues.On the other hand, pass through the use of adjusting TPGS
Amount, can be convenient the partial size of regulation nano particle, while can also play the role of a nanometer bridge, make the nano particle to be formed in organism
It is with good stability under physiological environment.
Detailed description of the invention
Fig. 1 is p (IB-alt-MAnh)-CD's made from the embodiment of the present invention1H-NMR figure.
Fig. 2 is p (IB-alt-MAnh)-CD to breast cancer cell MCF-7 cell strain and adriamycin breast carcinoma cell strain
The Toxic test results chart of MCF-7/ADR cell.
Fig. 3 is mPEG-DOX's made from the embodiment of the present invention1H-NMR figure.
The nano particle diameter point that Fig. 4 A-4C measures for DLS under the conditions of paclitaxel concentration different in the embodiment of the present invention
Butut and transmission electron microscope results；Wherein, Fig. 4 A indicate PTX concentration be 0.5mg/ml when gained nano particle diameter distribution map and its
Transmission electron microscope, Fig. 4 B indicate that gained nano particle diameter distribution map and its transmission electron microscope when PTX concentration is 1mg/ml, Fig. 4 C indicate
Gained nano particle diameter distribution map and its transmission electron microscope when PTX concentration is 2mg/ml.
Fig. 5 is the FT-IR map of nano particle made from the embodiment of the present invention.
Specific embodiment
Below by embodiment, the present invention is described in detail, so that the features and advantages of the present invention become apparent from.But it answers
This points out that for embodiment for understanding design of the invention, the scope of the present invention is not limited only to reality listed herein
Apply example.
Such as be not particularly illustrated, raw material used in embodiment be commercial product, it is used operation be this field
Routine operation.
The preparation of the adriamycin nano particle of embodiment size tunable
1, the preparation of poly- (isobutene-alt- maleic anhydride) modified beta-cyclodextrin (p (IB-alt-MAnh)-CD)
(1) by poly- (isobutene-alt- maleic anhydride), (p (IB-alt-MAnh), Mn (0.5K-1K) is dissolved in DMSO, dense
Degree is 5-15mg/ml；
(2) 1- ethyl-(3- dimethylaminopropyl) 2-3 times of maleic anhydride of carbodiimide hydrochloride molar ratio is added
Repeat chain number；
(3) pH to 8.0-9.0 of acquired solution is adjusted；
(4) N- hydroxysuccinimide (NHS) (EDC:NHS molar ratio=1:1) is added in 10-20min；
(5) hexamethylene diamine-beta-cyclodextrin is dissolved in DMSO (concentration 0.01-0.1mg/ml), magnetic agitation, obtains oneself two
Amine-beta-cyclodextrin solution；
(6) 15-20min after NHS is added in step (4), by the resulting solution containing p (IB-alt-MAnh) with 60-80
Drop/minute speed is added in hexamethylene diamine-beta-cyclodextrin solution of step (5), is vigorously stirred simultaneously, 48-72 is stirred at room temperature
Hour；
(7) the resulting solution of step (6) is subjected to phosphate buffer dialysis (pH 8.0-9.0) 36-48 hours,
(8) freeze-drying obtains white powder solid, is placed in -20 DEG C of preservations.
Shown in the following schema of the reaction process:
Reaction product p (IB-alt-MAnh)-CD, which is dissolved in deuterium oxide, to be done1H-NMR, as a result as shown in Figure 1.
For the biocompatibility for further exploring the substance, selecting cell is human breast carcinoma cell lines MCF-7 and MCF-
7ADR cell tested (referring to [1] R.Namgung, Y.Mi Lee, J.Kim, Y.Jang, B.Lee, I.Kim, P.Sokkar,
Y.M.Rhee,A.S.Hoffman,W.J.Kim,Poly-cyclodextrin and poly-paclitaxel nano-
assembly for anticancer therapy.Nature Communications 5(2014).[2]X.Xu,X.Chen,
Z.Wang,X.Jing,Ultrafine PEG–PLA fibers loaded with both paclitaxel and
doxorubicin hydrochloride and their in vitro cytotoxicity.Eur J Pharm
Biopharm 72 (1) (2009) 18-25.), as a result as shown in Fig. 2, abscissa indicates that p (IB-alt-MAnh)-CD's is dense in figure
Degree, ordinate indicate the cell activity to cell line.
2, the preparation of compound mPEG-DOX
(1) doxorubicin hydrochloride is dissolved in dimethyl sulfoxide (concentration 1-100mg/ml), magnetic agitation；
(2) appropriate triethylamine is added, is 1.5 times of equivalents of doxorubicin hydrochloride；
(3) NaOH solution is added and adjusts pH value of solution to alkaline (pH=8.5-9.0)；
(4) mPEG-HZ (Mw=2000-20000) is added, room temperature is protected from light, magnetic agitation 72h；
(5) a large amount of ether are added and are precipitated (10-15 times of liquor capacity)；
(6) it is dried in vacuo, obtains mPEG-DOX red powder, be placed in -20 DEG C of preservations.
The reaction process shows following schema:
Product mPEG-DOX using deuterated dimethyl sulfoxide as solvent,1H-NMR result is as shown in Figure 3.
3, the preparation of p (IB-alt-MAnh)-CD/mPEG-DOX nano particle
(1) p (IB-alt-MAnh) (10mg), mPEG-DOX (0.2mg) are dissolved in deionized water 2ml；
(2) pH to 8.0-9.0 is adjusted, room temperature is protected from light, ultrasound, 60~100W, 20K HZ；
(3) it is freeze-dried, obtains powder-like solid；
(4) by the solid powder after freeze-drying, it is dissolved in deionized water, concentration 3mg/ml；
(5) ultrasonic, 60~100W, 20K HZ, 10-20min are labeled as A；
(6) by Paclitaxel (PTX) (respectively 1mg/ml, 2mg/ml, 5mg/ml), vitamin E polyethylene glycol amber
Acid esters (TPGS) (mass ratio TPGS:PTX=2:1) is dissolved in dehydrated alcohol, is sufficiently stirred, and is labeled as B；
(7) (1.0-1.5ml/min) is added dropwise in A in B by micro-injection pump, is vigorously stirred simultaneously, is surpassed after being added completely into
Sound 60-100W, 20K HZ 10-20min；
(8) room temperature is protected from light, and magnetic agitation for 24 hours, makes dehydrated alcohol volatilize completely；
(9) 0.45 μm of membrane filtrations；
(10) 14000rpm, 10-15min centrifugation；
(11) supernatant is removed, precipitating is resuspended, ultrasonic (100W, 15min).
Survey dynamic light scattering (Malvern ZS90), as a result as shown in figs. 4 a-4 c, respectively indicate PTX concentration be 1mg/ml,
Under the conditions of 2mg/ml, 5mg/ml, dynamic light scattering measures nano particle diameter size, and gained is received when PTX concentration is 0.5mg/ml
Rice grain average grain diameter is 88.7 ± 4.5nm, when PTX concentration is 1mg/ml gained nano particle average grain diameter be 136.5 ±
The gained nano particle grain that is averaged is 214.5 ± 7.4nm when 6.1nm, PTX concentration are 2mg/ml；Phosphotungstic acid dyeing, transmission electron microscope inspection
Survey nano particle form.In addition, the FT-IR of Fig. 5 is the result shows that contain p (IB-alt-MAnh)-CD, mPEG- in nano particle
HZ、TPGS、PTX。
By embodiment it is found that nano particle of the invention can control the partial size of nano particle by the amount of kernel taxol,
Thus make its size tunable, to be conducive to enhance the stability of nano particle.
Unless limited otherwise, term used herein is the normally understood meaning of those skilled in the art.
Embodiment described in the invention is merely for exemplary purpose, the protection scope being not intended to limit the invention,
Those skilled in the art can be made within the scope of the invention various other replacements, changes and improvements, thus, the present invention is not limited to
Above embodiment, and be only defined by the claims.
Claims (11)
1. a kind of adriamycin nano particle of size tunable, which is characterized in that with Polyethylene glycol vitamin E succinate be interior
Core is passed through described in self assembly package as the modified beta-cyclodextrin of polyethylene glycol-adriamycin and poly- (isobutene-alt- maleic anhydride)
Kernel is formed, wherein includes paclitaxel nano crystal in the kernel.
2. adriamycin nano particle according to claim 1, which is characterized in that the polyethylene glycol VE succinic acid
The quality of ester kernel is the total matter of beta-cyclodextrin that the polyethylene glycol-adriamycin and poly- (isobutene-alt- maleic anhydride) are modified
0.05~20 times of amount.
3. adriamycin nano particle according to claim 2, which is characterized in that the polyethylene glycol VE succinic acid
The quality of ester kernel is the total matter of beta-cyclodextrin that the polyethylene glycol-adriamycin and poly- (isobutene-alt- maleic anhydride) are modified
0.1~10 times of amount.
4. adriamycin nano particle according to claim 3, which is characterized in that the polyethylene glycol VE succinic acid
The quality of ester kernel is the total matter of beta-cyclodextrin that the polyethylene glycol-adriamycin and poly- (isobutene-alt- maleic anhydride) are modified
0.2~5 times of amount.
5. adriamycin nano particle according to claim 1, which is characterized in that the poly- (isobutene-alt- maleic acid
Acid anhydride) modified beta-cyclodextrin is poly- (isobutene-alt- maleic anhydride) and hexamethylene diamine-beta-cyclodextrin as obtained by coupling reaction.
6. adriamycin nano particle according to claim 5, which is characterized in that the poly- (isobutene-alt- maleic acid
Acid anhydride) average molecular weight 5000~10000.
7. adriamycin nano particle according to claim 1, which is characterized in that poly- second in the polyethylene glycol-adriamycin
The degree of polymerization of glycol is 45~450.
8. adriamycin nano particle according to claim 1-7, which is characterized in that the adriamycin nano particle
It also include one of surfactant, emulsifier or a variety of.
9. the preparation method of any one of the claim 1-8 adriamycin nano particle, which comprises the following steps:
S1: certainly by the progress soluble in water of the modified beta-cyclodextrin of polyethylene glycol-adriamycin and poly- (isobutene-alt- maleic anhydride)
Assembling, freeze-drying obtain supramolecular complex；
S2: Polyethylene glycol vitamin E succinate and taxol are dissolved in dehydrated alcohol, emulsion is made；
S3: the resulting supramolecular complex of step S1 is soluble in water, then emulsion obtained by step S2 is added thereto, surpass
Sound volatilizes dehydrated alcohol, is centrifuged after 0.45 μm of membrane filtration up to the adriamycin nano particle.
10. preparation method according to claim 9, which is characterized in that the polyethylene glycol-adriamycin with it is described poly- (different
Butylene-alt- maleic anhydride) mass ratio of modified beta-cyclodextrin is 1:50~60.
11. preparation method according to claim 9, which is characterized in that in the step S1, by polyethylene glycol-adriamycin
Modified beta-cyclodextrin is soluble in water with poly- (isobutene-alt- maleic anhydride), and adjusting pH value is 8.0~9.0, carries out from group
Dress.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015105749711 | 2015-09-10 | ||
| CN201510574971 | 2015-09-10 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106511297A CN106511297A (en) | 2017-03-22 |
| CN106511297B true CN106511297B (en) | 2019-05-21 |
Family
ID=58343863
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610819358.6A Expired - Fee Related CN106511297B (en) | 2015-09-10 | 2016-09-12 | A kind of adriamycin nano particle of size tunable and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106511297B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107551276A (en) * | 2017-10-23 | 2018-01-09 | 锡山区东港全宝机械经营部 | Antineoplastic carries adriamycin α cyclodextrin pressurization vibrations parcel preparation technology |
| CN115960834B (en) * | 2023-03-07 | 2023-06-09 | 浙江省肿瘤医院 | PD-1/PTX combined PD-1 drug resistance model establishment method |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103976950A (en) * | 2014-05-21 | 2014-08-13 | 华中科技大学 | Adriamycin nano drug delivery system as well as preparation method and application thereof |
-
2016
- 2016-09-12 CN CN201610819358.6A patent/CN106511297B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103976950A (en) * | 2014-05-21 | 2014-08-13 | 华中科技大学 | Adriamycin nano drug delivery system as well as preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 环糊精包合作用组装大分子网络;王杰;《化工进展》;20081005;第27卷(第10期);第1558页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106511297A (en) | 2017-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sur et al. | Recent developments in functionalized polymer nanoparticles for efficient drug delivery system | |
| Del Prado-Audelo et al. | Chitosan-decorated nanoparticles for drug delivery | |
| Niu et al. | A novel chitosan-based nanomedicine for multi-drug resistant breast cancer therapy | |
| Dyawanapelly et al. | Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins | |
| Xu et al. | pH-Responsive nanoparticles based on cholesterol/imidazole modified oxidized-starch for targeted anticancer drug delivery | |
| Agrawal et al. | Bioadhesive micelles of d-α-tocopherol polyethylene glycol succinate 1000: Synergism of chitosan and transferrin in targeted drug delivery | |
| Qian et al. | Peptide functionalized dual-responsive chitosan nanoparticles for controlled drug delivery to breast cancer cells | |
| Muhamad12 et al. | Designing polymeric nanoparticles for targeted drug delivery system | |
| CN107308458B (en) | Targeted hybrid nano system and preparation method and application thereof | |
| Tao et al. | Novel delivery of mitoxantrone with hydrophobically modified pullulan nanoparticles to inhibit bladder cancer cell and the effect of nano-drug size on inhibition efficiency | |
| Meghani et al. | Design and evaluation of clickable gelatin-oleic nanoparticles using fattigation-platform for cancer therapy | |
| JP2014518862A (en) | Polymer nanoparticles for drug delivery | |
| Khan et al. | Advancements in dextran-based nanocarriers for treatment and imaging of breast cancer | |
| Luo et al. | pH-responsive stearic acid-O-carboxymethyl chitosan assemblies as carriers delivering small molecular drug for chemotherapy | |
| Liu et al. | Bio-responsive Bletilla striata polysaccharide-based micelles for enhancing intracellular docetaxel delivery | |
| TW201628610A (en) | Pharmaceutical compositions, preparation and uses thereof | |
| Castro et al. | Docetaxel in chitosan-based nanocapsules conjugated with an anti-Tn antigen mouse/human chimeric antibody as a promising targeting strategy of lung tumors | |
| CN107096036A (en) | A kind of preparation method and applications of pH responsive types hyaluronic acid Doxorubicin nano-prodrug | |
| Cheng et al. | Hydrogen-bonded supramolecular micelle-mediated drug delivery enhances the efficacy and safety of cancer chemotherapy | |
| CN106511297B (en) | A kind of adriamycin nano particle of size tunable and preparation method thereof | |
| Li et al. | Biocompatible supramolecular pseudorotaxane hydrogels for controllable release of doxorubicin in ovarian cancer SKOV-3 cells | |
| Nath et al. | Modern developments of nano based drug delivery system by combined with phytochemicals-presenting new aspects | |
| Yu et al. | GSH-responsive curcumin/doxorubicin encapsulated Bactrian camel serum albumin nanocomposites with synergistic effect against lung cancer cells | |
| CN109771660A (en) | It is a kind of to respond the preparation of pectin-adriamycin/tripterine nanometer particle with pH | |
| CN111450265B (en) | Targeting pH-sensitive polymer vesicle loaded with gold-drug compound and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20190521 Termination date: 20210912 |