CN108926531A - A kind of reduction and the nano-micelle of pH dual responsiveness and the preparation method and application thereof - Google Patents
A kind of reduction and the nano-micelle of pH dual responsiveness and the preparation method and application thereof Download PDFInfo
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- CN108926531A CN108926531A CN201810724456.0A CN201810724456A CN108926531A CN 108926531 A CN108926531 A CN 108926531A CN 201810724456 A CN201810724456 A CN 201810724456A CN 108926531 A CN108926531 A CN 108926531A
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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
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Abstract
The nano-micelle of a kind of reduction and pH dual responsiveness, has hydrophilic shell and hydrophobic inner core, hydrophilic shell is poly- oxazoline, and hydrophobic inner core is polyurethane, is by amphipathic urethane by being self-assembly of.The hydrophobic segment of amphipathic urethane is the polyurethane containing the sensitive disulfide bond of reduction, and hydrophilic segment is the poly- oxazoline with pH responsiveness.Application of the nano-micelle of a kind of reduction of the invention and pH dual responsiveness as pharmaceutical carrier, nano-micelle is intracellular reducing environment and acidic environment as the degradation environment of the application of pharmaceutical carrier.After the nano-micelle of a kind of reduction of the invention and pH dual responsiveness enters tumour cell, the fast degradation under the double action of cell reductive condition and endosome/lysosome acidic environment, drug is fast released out, the drug release for solving pharmaceutical carrier is slow, the problem of being easy to produce drug resistance improves curative effect.
Description
Technical field
The invention belongs to chemical synthesis and biomedicine field, the nano-micelle of a kind of specific reduction and pH dual responsiveness
And the preparation method and application thereof.
Background technique
Nano-micelle can improve the stability of hydrophobic anticancer drug in aqueous solution by solubilization, can carry simultaneously
Image-forming dye and drug realize the real time monitoring of observation therapeutic efficacy.Medicament-carried nano micelle can be applied to by passive target
Up to tumor locus, thus the toxic side effect of hydrophobic anticancer drug in the normal tissue is reduced, improves drug therapy cancer
Effect.These excellent characteristics of nano-micelle provide more effective medication for cancer chemotherapy.
Amphiphilic polymer passes through the medicines such as the aggregation such as nanoparticle, nano-micelle, polymer vesicle being self-assembly of
Although object carrier can extend the circulation time of pharmaceutical carrier in vivo, increase pharmaceutical carrier in the accumulation of tumor locus, often
Effectively the drug release contained cannot be come out, to reduce drug effect.According to the intracellular environment of tumour cell, exploitation tool
There is the nano-medicament carrier of environment-responsive (such as pH, temperature, redox), can effectively improve the release speed of drug
Rate reduces the toxic side effect of drug in vivo, improves the therapeutic effect of anticarcinogen.The biocompatibility of bio-medical material and
Biodegradable properties are key factor in need of consideration in clinical application, the good biocompatibility of polyurethane material, physics and chemistry
Matter is stablized, and has been widely used in biomedicine, such as heart valve, artificial blood vessel, artificial conduit.
Since poly- oxazoline has the characteristic of swelling under acidic environment, make this two using poly- oxazoline as hydrophilic section
The micella of close polyurethane assembling has pH responsiveness.This characteristic makes polyurethane carrier micelle in endosome/lyase of cell
(pH 5.0-5.5) can be swollen rapidly and discharge drug under the acidic environment of body.Existing list responsive polymer carrier micelle exists
The anticarcinogen (Yao, et al.RSC Adv.2016,6:9082-9089) of release 70% or so is often only capable of in for 24 hours, drug carries
Body is slowly and incomplete release drug causes tumor locus drug concentration too low, antitumor action decline, or even causes this medicine
The drug resistance of object.
Summary of the invention
The object of the present invention is to provide a kind of reduction and nano-micelle of pH dual responsiveness and the preparation method and application thereof,
It effectively cannot release medicine out to solve amphipathic copolymer by being self-assembly of pharmaceutical carrier, cause drug effect low
Problem.
To achieve the above object, technical scheme is as follows:
It is a kind of reduction and pH dual responsiveness nano-micelle, have hydrophilic shell and hydrophobic inner core, be by amphipathic
Urethane is by being self-assembly of.The hydrophobic segment of amphipathic urethane is the polyurethane containing the sensitive disulfide bond of reduction, hydrophilic
Segment is the poly- oxazoline with pH responsiveness.
Further, amphipathic urethane is the poly- poly- oxazoline of oxazoline-polyurethane-, and the hydrophilic shell is poly- oxazoline,
Poly- oxazoline molecular weight is 1500-10000Da, and the hydrophobic inner core is polyurethane, and the molecular weight of polyurethane is 2000-
50000Da。
The preparation method of above-mentioned amphipathic urethane, in inert atmosphere, end is the polyester-diol and two isocyanides of hydroxyl
Acid esters reacts synthesis of polyurethane performed polymer in organic solvent, is blocked with poly- oxazoline finally produced at room temperature later
Object.
Further, the polyester-diol is polycaprolactone, polycarbonate or polylactic acid；The diisocyanate is cystamine
Diisocyanate CDI, L-lysine ethyl ester diisocyanate LDI or hexamethylene diisocyanate HDI.
Further, further include the preparation of the poly- oxazoline: in inert atmosphere, methyl tosylate ring-opening polymerisation
2- ethyl -2- oxazoline obtains the poly- oxazoline.
The preparation method of the nano-micelle of a kind of above-mentioned reduction and pH dual responsiveness: the amphipathic urethane is first molten
In organic solvent, secondary water is instilled under the conditions of being stirred at room temperature, by being self-assembly of using poly- oxazoline as hydrophilic shell, poly- ammonia
Ester is the nano-micelle of hydrophobic inner core.
Application of the nano-micelle of a kind of above-mentioned reduction and pH dual responsiveness as pharmaceutical carrier.
Further, degradation environment when application of the nano-micelle as pharmaceutical carrier be intracellular reducing environment and/
Or acidic environment.
Further, reducing environment is environment existing for the molecule containing sulfydryl.
Further, the molecule containing sulfydryl is glutathione.
Compared with prior art, beneficial effects of the present invention:
1. amphipathic polyurethane backbone of the invention contains the sensitive disulfide bond of reduction, can be by amphipathic urethane
Self assembly obtains stable reduction responsive nano micella, with lesser critical micelle concentration, in extracellular and blood
It is not easy to dissociate, ensure that the drug substance stable of nano-micelle encapsulating, overcome drug and be easily compromised in vivo, deliver low efficiency, follow
The problem of the deficiencies of ring time is short；
It, can be in the cell with pH responsiveness 2. the hydrophilic section of amphipathic urethane of the invention is poly- oxazoline
Contain quick release under body/lysosome acidic environment.
After 3. the nano-micelle of a kind of reduction of the invention and pH dual responsiveness enters tumour cell, in cell reproducibility
Fast degradation under the double action of condition and endosome/lysosome acidic environment, drug are fast released out, solve medicine
The problem of drug release of object carrier is slow, is easy to produce drug resistance, improves curative effect.
Specific embodiment:
Embodiment 1: the synthesis (Mn=1000Da) of polycaprolactone glycol
It is starting material and dithio glycol (HES) in octanoic acid that polycaprolactone glycol (PCL), which is with caprolactone (ε-CL),
Stannous (Sn (Oct)2) catalysis under ring-opening polymerisation obtain.
Concrete operations are as follows:
Under nitrogen protection, 42.1mL toluene, HES are sequentially added into the confined reaction bottle for having stirrer in glove box
(0.102g, 0.6590mmol), Sn (Oct.)2(0.081g, 0.1997mmol), ε-CL (7.22g, 63.27mmol) then will
Removal glove box is sealed in reactor, is placed in 100 DEG C of oil bath and continues polymerization reaction for 24 hours.After reaction, reaction solution is dense
Be deposited in after contracting in ice ether, filter, vacuum drying for 24 hours to get arrive product PCL-SS-PCL.Yield: 85.1%.
Embodiment 2: the synthesis (Mn=5000Da) of polymer P EtOz-OH
The preparation of hydrophilic section polymer poly oxazoline PEtOz-OH is blocked, the poly- oxazoline is polymer, and synthesis is
Under nitrogen protection, methyl tosylate ring-opening polymerisation 2- ethyl -2- oxazoline.Concrete operations are as follows:
Methyl tosylate (0.34g, 1.834mmol) and 2- ethyl -2- oxazoline are added in dry acetonitrile
Mixture is heated to 100 DEG C and is stirred to react for 24 hours by (10g, 100.9mmol).It is cooled to room temperature, is added after reaction
4h is stirred at room temperature in 0.1mL KOH (1N), with ice ether sedimentation separation.By polymer P EOZ-OH with deionized water dialysis (MWCO:
It 3500g/mol) purifies two days, during which replacement dialysis medium is finally freeze-dried to obtain product PEtOz-OH.Yield:
87.6%.
Embodiment 3: the synthesis of polymer P EtOz-PU (SS)-PEtOz
The preparation method of the amphipathic urethane is: polycaprolactone glycol and di-isocyanate reaction are used first at 65 DEG C
Synthesis of polyurethane performed polymer blocks to obtain final product with the poly- oxazoline of terminal hydroxyl at room temperature later.
Concrete operations are as follows:
It under nitrogen protection, will to be dissolved in 10mL anhydrous after the polycaprolactone glycol of 1g, that is, 1mmol toluene azeotropic band water
DMF, is added CDI (1.05mmol, 0.214g) later, after being stirred to react for 24 hours under the conditions of 65 DEG C, take poly- oxazoline (0.1mmol,
It 0.5g) is dissolved in 5mL anhydrous DMF, is instilled under the conditions of ice-water bath in above-mentioned solution, react 48h at room temperature.After reaction,
For concentration and settlement in methanol/ice ether, vacuum drying obtains PEtOz-PU (SS)-PEtOz；The methanol/ice ether is v/
V, 1:10.Yield: 54.1%.
Embodiment 4: the system of poly- oxazoline-polyurethane (SS)-poly- oxazoline (PEtOz-PU (SS)-PEtOz) nano-micelle
It is standby
The nano-micelle of polymer P EtOz-PU (SS)-PEtOz is prepared by dialysis process.Detailed process is: 2mg is gathered
It closes object and is dissolved in 1mL dimethyl sulfoxide, under 25 DEG C of stirring conditions, 1.5mL deionized water is added dropwise thereto.Obtained solution stirring 1
After hour, (SPECTRA/POR, MWCO:3500) is fitted into bag filter, with deionized water dialysis 24 hours.
Embodiment 5: the preparation of the poly- poly- oxazoline of oxazoline-polyurethane-(PEtOz-PU-PEtOz) nano-micelle of control group
Polymer P EtOz-PU-PEtOz nano-micelle is prepared by dialysis process.Detailed process is: by 2mg polymer
PEtOz-PU-PEtOz is dissolved in 1mL dimethyl sulfoxide, and under 25 DEG C of stirring conditions, 1.5mL deionized water is added dropwise thereto.It obtains
Solution stir 1 hour after, be fitted into preprepared bag filter (SPECTRA/POR, MWCO:3500), use deionized water
Dialysis 24 hours.
Amphipathic urethane micelle is prepared according to embodiment 4 and example 5, and tests the size for being formed by nano-micelle and divides
Cloth, the results are shown in Table 1:
The amphipathic urethane nano-micelle of the different hydrophobic segments of table 1
Embodiment 6: the deoxidization, degradation of poly- oxazoline-polyurethane (the SS)-poly- oxazoline nano-micelle of dual responsiveness
In the present embodiment, situation existing for intracellular GSH is simulated with DTT solution (10mM).Specifically, under nitrogen protection,
The DTT weighed up is added to the hyaloid of 2.0mL PEtOz-PU (SS)-PEtOz polymer nano micelle (0.001 mg/ml)
In product pond, making the concentration of final DTT is 10mM.To be added without the micella of DTT as control.Use rubber in latter two right glass sample pond
Rubber plug seals, and shakes up, and is placed in 37 DEG C of constant-temperature tables (200rpm), surveys micellar particle size by DLS at seclected time, 37 DEG C
Variation.DLS reaches 761nm after 8h the results show that micella partial size after 4h by 110nm increases to 280nm.And micella itself
Partial size is basically unchanged after 24h, illustrates that this urethane micelle has good reduction responsiveness, restores item existing for the 10mM DTT
Under part, disulfide bonds, micella is swollen, and partial size constantly increases.
Embodiment 7: packing model small molecule anticancer drug adriamycin
PEtOz-PU-PEtOz and PEtOz-PU (SS)-PEtOz micella are all to pass through dialysis to the encapsulating of anticancer drug
It realizes.By taking PEtOz-PU (SS)-PEtOz as an example, takes the polymer of 2.4mg to be dissolved in 1mL dimethyl sulfoxide, will design
Drugloading rate needed for adriamycin be added thereto, after ultrasonic 0.5h, under the conditions of being stirred at room temperature, into dimethyl sulfoxide solution slowly
1.5mL secondary water is added dropwise, ultrasound 1h again after being added dropwise.Then mixed solution is moved in bag filter (MWCO:3500), is dialysed
It takes out afterwards for 24 hours.
The determination of encapsulation rate of the DOX in polymer nano micelle: taking a certain amount of medicament-carried nano micelle, first passes through freezing
Then seasoning water removal is added 0.5mL dimethyl sulfoxide and dissolves micella, then ultrasound 1 hour, 20 μ L of the solution is taken to be added to 3mL bis-
In first sulfoxide, by fluorometric investigation, in conjunction with the standard curve computational envelope rate of adriamycin.
Encapsulation rate=(quality of quality/investment adriamycin of adriamycin in nano-micelle) × 100%
The nano-micelle of the different drugloading rate of two kinds of polymer is prepared according to embodiment 7, and tests gained nano-micelle
Size, distribution and encapsulation rate etc., the results are shown in Table 2:
The carrier micelle of 2 two kinds of polymer difference drugloading rate of table
Embodiment 8: it is loaded with the triggering release of the carrier micelle of adriamycin
In the present embodiment, with sodium acetate buffer simulate intracellular endosome/lysosomal acid environment (pH 5.0~
5.5).PEtOz-PU (the SS)-PEtOz carrier micelle for being loaded with DOX is divided into two parts, is fitted into corresponding bag filter, the former quilt
The sodium acetate buffer (20mM, pH 5.0) that 40mL contains 10mM DTT is immersed, the latter is dipped into the PB (20mM) of 40mL,
It is placed in 37 DEG C of constant-temperature tables (200rpm).It is used to measure its every the dialyzate outside the bag filter that certain time takes setting volume glimmering
Luminous intensity, and supplement the fresh liquid of respective volume.Persistently test 24 hours.
The result shows that: it is loaded with the nano-micelle of the dual responsiveness of the DOX sodium acetate buffer at 10mM DTT, 37 DEG C
In, PEtOz-PU (SS)-PEtOzz carrier micelle can rapidly release DOX, and burst size is up to 95%.In no DTT
Under the conditions of existing PB (20mM, pH 7.4), PEtOz-PU (SS)-PEtOz polymer medicament carrying micelle only releases in for 24 hours
25% DOX.The experimental results showed that PEtOz-PU (SS)-PEtOz carrier micelle containing disulfide bond, there is intracellular environment
Responsiveness can quickly discharge drug in environment in vivo, improve curative effect.
Claims (10)
1. the nano-micelle of a kind of reduction and pH dual responsiveness, including hydrophilic shell and hydrophobic inner core, which is characterized in that described double
The nano-micelle of weight sensibility by amphipathic urethane by being self-assembly of, the hydrophobic segment of the amphipathic urethane be containing
The polyurethane for the disulfide bond for having reduction sensitive, the hydrophilic segment of the amphipathic urethane are the poly- oxazole with pH responsiveness
Quinoline.
2. the nano-micelle of a kind of reduction according to claim 1 and pH dual responsiveness, which is characterized in that the amphiphilic
Property polyurethane be the poly- poly- oxazoline of oxazoline-polyurethane-, the hydrophilic shell be poly- oxazoline, poly- oxazoline molecular weight be 1500-
10000Da, the hydrophobic inner core are polyurethane, and the molecular weight of polyurethane is 2000-50000Da.
3. the preparation method of amphipathic urethane described in claim 1, which is characterized in that in inert atmosphere, end is hydroxyl
The polyester-diol of base reacts synthesis of polyurethane performed polymer with diisocyanate in organic solvent, later at room temperature with poly-
Oxazoline blocks to obtain final product.
4. the preparation method of amphipathic urethane according to claim 3, which is characterized in that the polyester-diol is to gather oneself
Lactone, polycarbonate or polylactic acid；The diisocyanate is cystamine diisocyanate CDI, L-lysine ethyl ester diisocyanate
Ester LDI or hexamethylene diisocyanate HDI.
5. the preparation method of amphipathic urethane according to claim 3, which is characterized in that further include the poly- oxazoline
Preparation: in inert atmosphere, methyl tosylate ring-opening polymerisation 2- ethyl -2- oxazoline obtains the poly- oxazoline.
6. the preparation method of the nano-micelle of a kind of reduction described in claim 1 and pH dual responsiveness, which is characterized in that will
The amphipathic urethane is first molten in organic solvent, instills secondary water under the conditions of being stirred at room temperature, by be self-assembly of with
Poly- oxazoline is hydrophilic shell, and polyurethane is the nano-micelle of hydrophobic inner core.
7. application of the nano-micelle of a kind of reduction of any of claims 1 or 2 and pH dual responsiveness as pharmaceutical carrier.
8. application of the nano-micelle of a kind of reduction according to claim 7 and pH dual responsiveness as pharmaceutical carrier,
It is characterized in that, the nano-micelle is intracellular reducing environment and/or acidic environment as the degradation environment of pharmaceutical carrier.
9. application of the nano-micelle of a kind of reduction according to claim 8 and pH dual responsiveness as pharmaceutical carrier,
It is characterized in that, the reducing environment is environment existing for the molecule containing sulfydryl.
10. application of the nano-micelle of a kind of reduction according to claim 9 and pH dual responsiveness as pharmaceutical carrier,
It is characterized in that, the molecule containing sulfydryl is glutathione.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228218A (en) * | 2020-02-21 | 2020-06-05 | 江苏师范大学 | Temozolomide nano prodrug micelle and preparation method and application thereof |
| CN111450265A (en) * | 2020-06-04 | 2020-07-28 | 东南大学 | Targeting pH-sensitive polymer vesicle loaded with gold-drug compound and preparation method thereof |
| CN112315910A (en) * | 2020-11-10 | 2021-02-05 | 南开大学 | Nano-carrier with dual responses of pH and hypoxic and preparation method and application thereof |
| CN113136017A (en) * | 2021-04-02 | 2021-07-20 | 中国科学院合肥物质科学研究院 | Polyurethane with pH response and self-healing performance and preparation method thereof |
| CN114181360A (en) * | 2021-12-08 | 2022-03-15 | 南京工业大学 | Ultrasonic wave stimulus response polyurethane and preparation method thereof |
| CN115010913A (en) * | 2022-06-17 | 2022-09-06 | 广东工业大学 | PH/reduction dual-response polymer micelle and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103495203A (en) * | 2013-09-09 | 2014-01-08 | 西安交通大学 | Reductively biodegradable type honeycomb polyurethane support, and preparation method and application thereof |
| CN105247388A (en) * | 2013-05-31 | 2016-01-13 | 帝斯曼知识产权资产管理有限公司 | Macromers comprising pendant polyoxazoline groups and end groups |
| CN105348157A (en) * | 2015-12-18 | 2016-02-24 | 苏州大学 | Cystamine diisocyanate monomer, cystamine diisocyanate monomer based polymers as well as preparation method and application of cystamine diisocyanate monomer |
| CN105968370A (en) * | 2016-06-22 | 2016-09-28 | 国家纳米科学中心 | Triple disulfide-bond linked polyethylene glycol-polycaprolactone triblock copolymer as well as preparation method and application thereof |
| CN106727307A (en) * | 2016-12-12 | 2017-05-31 | 江苏师范大学 | A kind of preparation and application for reducing sensitive nano-micelle |
-
2018
- 2018-07-04 CN CN201810724456.0A patent/CN108926531B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105247388A (en) * | 2013-05-31 | 2016-01-13 | 帝斯曼知识产权资产管理有限公司 | Macromers comprising pendant polyoxazoline groups and end groups |
| CN103495203A (en) * | 2013-09-09 | 2014-01-08 | 西安交通大学 | Reductively biodegradable type honeycomb polyurethane support, and preparation method and application thereof |
| CN105348157A (en) * | 2015-12-18 | 2016-02-24 | 苏州大学 | Cystamine diisocyanate monomer, cystamine diisocyanate monomer based polymers as well as preparation method and application of cystamine diisocyanate monomer |
| CN105968370A (en) * | 2016-06-22 | 2016-09-28 | 国家纳米科学中心 | Triple disulfide-bond linked polyethylene glycol-polycaprolactone triblock copolymer as well as preparation method and application thereof |
| CN106727307A (en) * | 2016-12-12 | 2017-05-31 | 江苏师范大学 | A kind of preparation and application for reducing sensitive nano-micelle |
Non-Patent Citations (2)
| Title |
|---|
| JINWEN LI等: "Poly(2-ethyl-2-oxazoline)-Doxorubicin Conjugate-Based Dual Endosomal pH-Sensitive Micelles with Enhanced Antitumor Efficacy", 《BIOCONJUGATE CHEMISTRY》 * |
| LELE WANG等: "Coordinated pH/redox dual-sensitive and hepatoma-targeted multifunctional polymeric micelle system for stimuli-triggered doxorubicin release: Synthesis, characterization and in vitro evaluation", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111228218A (en) * | 2020-02-21 | 2020-06-05 | 江苏师范大学 | Temozolomide nano prodrug micelle and preparation method and application thereof |
| CN111228218B (en) * | 2020-02-21 | 2021-11-02 | 江苏师范大学 | Temozolomide nano prodrug micelle and preparation method and application thereof |
| CN111450265A (en) * | 2020-06-04 | 2020-07-28 | 东南大学 | Targeting pH-sensitive polymer vesicle loaded with gold-drug compound and preparation method thereof |
| CN111450265B (en) * | 2020-06-04 | 2022-09-23 | 东南大学 | Targeting pH-sensitive polymer vesicle loaded with gold-drug compound and preparation method thereof |
| CN112315910A (en) * | 2020-11-10 | 2021-02-05 | 南开大学 | Nano-carrier with dual responses of pH and hypoxic and preparation method and application thereof |
| CN113136017A (en) * | 2021-04-02 | 2021-07-20 | 中国科学院合肥物质科学研究院 | Polyurethane with pH response and self-healing performance and preparation method thereof |
| CN113136017B (en) * | 2021-04-02 | 2022-08-09 | 中国科学院合肥物质科学研究院 | Polyurethane with pH response and self-healing performance and preparation method thereof |
| CN114181360A (en) * | 2021-12-08 | 2022-03-15 | 南京工业大学 | Ultrasonic wave stimulus response polyurethane and preparation method thereof |
| CN115010913A (en) * | 2022-06-17 | 2022-09-06 | 广东工业大学 | PH/reduction dual-response polymer micelle and preparation method and application thereof |
| CN115010913B (en) * | 2022-06-17 | 2023-05-26 | 广东工业大学 | PH/reduction dual-response polymer micelle and preparation method and application thereof |
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