CN110591016B - MAA-co-DAA-co-PEGMA copolymer and preparation method and application thereof - Google Patents
MAA-co-DAA-co-PEGMA copolymer and preparation method and application thereof Download PDFInfo
- Publication number
- CN110591016B CN110591016B CN201911016536.1A CN201911016536A CN110591016B CN 110591016 B CN110591016 B CN 110591016B CN 201911016536 A CN201911016536 A CN 201911016536A CN 110591016 B CN110591016 B CN 110591016B
- Authority
- CN
- China
- Prior art keywords
- daa
- maa
- solution
- pegma
- tbdms
- 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.)
- Active
Links
Images
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
- C08F283/06—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals
- C08F283/065—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polyethers, polyoxymethylenes or polyacetals on to unsaturated polyethers, polyoxymethylenes or polyacetals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Inorganic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention belongs to the technical field of drug carriers, and discloses an MAA‑co‑DAA‑co‑PEGMA copolymer and a preparation method and application thereof. The structural formula is as follows:
. The preparation method comprises the following steps: respectively dissolving TBDMS-DAA and BACy in DMF to obtain TBDMS-DAA solution and BACy solution; dissolving TBAF in THF to obtain a TBAF solution; adding MAA, TBDMS-DAA solution, PEGMA, BACy solution and SDS into water in nitrogen atmosphere, mixing, heating to 40-100 ℃ under stirring, adding APS, reacting for 5-10 h, centrifuging, washing, and freeze-drying; adding the dried product into TBAF solution, stirring, centrifuging to collect precipitate, washing with THF, washing with water, and freeze-drying to obtain MAA‑co‑DAA‑co‑PEGMA copolymer. MAA of the invention‑co‑DAA‑co‑The PEGMA copolymer is used as a drug carrier, has high drug loading rate and can solve the problem of hydrophobicity of the drug.
Description
Technical Field
The invention belongs to the technical field of drug carriers, and particularly relates to an MAA-co-DAA-co-PEGMA copolymer, and a preparation method and application thereof.
Background
Cancer has long been a significant disease threatening human life, and a study reported by the U.S. cable television news network (CNN) has shown that: the number of cancer patients in the world is still continuously increasing, and nearly 1810 ten thousand cancer diagnosis cases exist in 2018 alone, wherein 992 ten thousand people die of cancer, and the cancer death rate is more than half. According to the report released by the world health organization international cancer research institution on 9/12 days, by the end of this century, cancer will become the first killer worldwide and is the biggest obstacle to improving the life expectancy of people. Better treatment of cancer is achieved not only based on the high efficacy of anticancer drugs, but also the need for synergy of the antitumor drug delivery system and the high efficacy of drug release. Due to the high permeability and retention effect of tumor tissues, the nanoparticles are preferentially enriched at the tumor focus part, the passive targeted therapy of the tumor is realized to a certain extent, and the research heat of researchers on a targeted drug delivery system is stimulated.
The Hu topic group utilizes mesoporous silicon dioxide nano material with polystyrene latex coated on the surface to load Bortezomib (BTZ) to prepare nanoparticles with the particle size of about 140 nm and the drug loading rate of 1.87 wt.%. Compared with free BTZ, the toxicity of H1299 non-small cell lung cancer cells of the drug-loaded nanoparticles is improved by 2.3 times, and in-vivo treatment experiments also show that the tumor inhibition effect of the drug-loaded nanoparticles is improved by about 1.5 times, but the cumulative release amount of the drug-loaded nanoparticles in phosphate buffer solution for 8 hours is about 68%, which shows that the drug-loaded nanoparticles are likely to have the problem of drug leakage under physiological conditions. The drug-loaded nanoparticles prepared by the authors by adopting a single emulsion technology have the drug-loaded efficiency of about 53%, the actual drug-loaded amount of BTZ is 5.1 wt%, and the particle size is 195 nm, the nanoparticles show obvious toxicity to S2-013 human pancreatic cancer cells, the half-inhibitory concentration is about 7.5 mM, and in vitro release data show that the PLGA nanoparticles can only release 25% of BTZ in 24 h.
In the past, BTZ nano-drugs have the defects of low drug loading, easy drug leakage in physiological environment, slow drug release in tumor cells, no targeting capability and the like.
Disclosure of Invention
The invention aims to provide an MAA-co-DAA-co-PEGMA copolymer, and a preparation method and application thereof.
In order to realize the purpose, the technical scheme adopted by the invention is as follows:
a MAA-co-DAA-co-PEGMA copolymer having the formula:
preferably, a, b, c and d are positive integers, and a: b: c: d = (1-32): 1: 2.
A preparation method of the MAA-co-DAA-co-PEGMA copolymer comprises the following steps:
(1) respectively dissolving TBDMS-DAA and BACy in DMF to obtain TBDMS-DAA solution and BACy solution; dissolving TBAF in THF to obtain a TBAF solution;
(2) adding MAA, TBDMS-DAA solution, PEGMA, BACy solution and SDS into water in nitrogen atmosphere, mixing, heating to 40-100 ℃ under stirring, adding APS, reacting for 5-10 h, centrifuging, washing, and freeze-drying;
(3) and (3) adding the product obtained in the step (2) into a TBAF solution, stirring, centrifuging, collecting precipitates, washing with THF, washing with water, and freeze-drying to obtain the MAA-co-DAA-co-PEGMA copolymer.
Preferably, the weight average molecular weight of PEGMA is 300-2000.
Preferably, in the step (1), the concentration of the TBDMS-DAA solution is 90-270 mg/mL, the concentration of the BACy solution is 50-170 mg/mL, and the concentration of the TBAF solution is 0.1-0.4 mol/L; in the step (2), the molar ratio of MAA, BACy, PEGMA and TBDMS-DAA is (1-32) to 1: 2, the total input amount of APS is (1-3)/1000 of the total mass of MAA, PEGMA and TBDMS-DAA, and the consumption of water is 10-15 times of the total volume of the TBDMS-DAA solution and the BACy solution; the concentration of SDS in the mixed solution (namely the mixed solution obtained by adding MAA, TBDMS-DAA solution, PEGMA, BACy solution and SDS into water and mixing) in the step (2) is 1.5-2.0 g/L; in the step (3), the amount of TBAF is 3-10 times of the amount of TBDMS-DAA added in the step (2) by mol.
An application of the MAA-co-DAA-co-PEGMA copolymer as a drug carrier.
In the invention: MAA is methacrylic acid, BACy is N, N' -bis (acryloyl) cystamine, PEGMA is polyethylene glycol methacrylate, TBDMS-DAA is tert-butyldimethylsilyl dopamine acrylamide, DMF is N, N-dimethylformamide, SDS is sodium dodecyl sulfate, APS is ammonium persulfate, TBAF is tetrabutylammonium fluoride, THF is tetrahydrofuran.
Has the advantages that: the MAA-co-DAA-co-PEGMA copolymer is used as a drug carrier, has high drug loading capacity, and can solve the problem of hydrophobicity of the drug; the cross-linking agent selects BACy to ensure that the carrier has higher degradability; after the copolymer carrier loads the drug, the release rate is greater than that of a neutral medium in the presence of acid and 10 mM glutathione, so that the copolymer has wide application prospect in the aspect of serving as an ideal drug delivery system.
Drawings
FIG. 1: TEM image of MAA-co-DAA-co-PEGMA copolymer obtained in inventive example 1;
FIG. 2: DLS diagram of the MAA-co-DAA-co-PEGMA copolymer obtained in example 1 of the present invention;
FIG. 3: an infrared spectrogram of the MAA-co-DAA-co-PEGMA copolymer obtained in the embodiment 1 of the invention;
FIG. 4: the XPS spectrogram of the MAA-co-DAA-co-PEGMA copolymer obtained in the example 1 of the invention: (a) full spectrum, (b) C1 spectrum, (C) O1 spectrum;
FIG. 5: the MAA-co-DAA-co-PEGMA copolymer obtained in example 1 of the present invention was tested for stability in PBS buffer (pH =7.4) and PBS + DMEM (1: 9, pH = 7.4);
FIG. 6: drug release profile of MAA-co-DAA-co-PEGMA copolymer @ BTZ.
Detailed Description
The following examples are intended to illustrate the invention in further detail, but are not to be construed as limiting the invention in any way; in the following examples, TBDMS-DAA can be prepared by reference to Lee S B, Gonza ́ lez-Cabenzas C, Kim K M, et al, protected-functionalized synthetic polymer as a substituted to substituted surface for a composition reduction [ J ]. Biomacromolecular modules, 2015, 16(8): 2265-2275, which differs from the preparation of TBDMS-DMA in that: replacing methacryloyl chloride with an equimolar amount of acryloyl chloride; BACy references S.jin, J.X.Wan, L.Z.Meng, X.X.Huang, J.Guo, L.Liu, C.C.Wang, Biodegradation and toxicity of protease/redox/pH stimulation-reactive PEGlated PMAA nanohydrogels for targeting drug delivery, ACS application. interface 7 (2015) 19843-; other materials used, unless otherwise specified, were purchased from conventional chemical companies and raw material suppliers.
Example 1
An MAA-co-DAA-co-PEGMA copolymer is prepared by the following steps:
the preparation steps are as follows:
(1) dissolving 0.27 g of TBDMS-DAA in 2 mL of DMF to obtain a TBDMS-DAA solution; dissolving 0.085 g of BACy in 1 mL of DMF to obtain a BACy solution; dissolving 2 mmol of TBAF in 10 mL of THF to obtain 0.2 mol/L TBAF solution;
(2) adding 0.492 g MAA, 0.198 g PEGMA (average molecular weight 300), 0.0692 g SDS, TBDMS-DAA solution obtained in the step (1) and BACy solution into 36 mL water under nitrogen atmosphere, mixing, heating to 80 ℃ under stirring, adding 0.001 g APS, reacting for 8 h, centrifuging, washing, and freeze-drying at-40 ℃;
(3) and (3) adding the product obtained in the step (2) into 10 mL of TBAF solution, stirring, centrifuging, collecting precipitate, washing with THF (tetrahydrofuran), washing with water, and freeze-drying at-45 ℃ to obtain the MAA-co-DAA-co-PEGMA copolymer.
FIG. 1 is a TEM image of a copolymer of MAA-co-DAA-co-PEGMA. As can be seen from fig. 1: the resulting MAA-co-DAA-co-PEGMA copolymer had a spherical structure with a diameter of about 170 nm and was monodisperse.
FIG. 2 is a DLS plot of MAA-co-DAA-co-PEGMA copolymer. As can be seen from fig. 2: the MAA-co-DAA-co-PEGMA copolymer shows stable and good dispersion stability in PBS at pH 7.4.
FIG. 3 is an infrared spectrum of a copolymer MAA-co-DAA-co-PEGMA. As can be seen from fig. 3: at 1240 cm -1 The characteristic peak of phenolic hydroxyl is important evidence for the existence of DAA functional monomer; 2565 cm -1 S-S stretching vibration adsorption proves the introduction of disulfide bond in the main chain of the polymer; meanwhile, a typical peak 1728 cm of carboxyl MAA exists -1 The introduction of MAA was demonstrated to be successful; furthermore, the characteristic adsorption is 1100 cm -1 The presence of PEG is demonstrated.
FIG. 4 is an XPS plot of MAA-co-DAA-co-PEGMA copolymer: (a) full spectrum, (b) C1 spectrum, (C) O1 spectrum. The C1s spectrum of the MAA-co-DAA-co-PEGMA is decomposed into 5 energy bands, in the 5 energy bands, the main component generates a carbon-carbon single bond (C-C) at 284.95 eV from the copolymer, and the characteristic band of 286.45 eV is the typical ether structure (C-O-C) of PEGMA monomers in the MAA-co-DAA-co-PEGMA; two distinct characteristic bands at 285.58 and 287.41 eV, amide structures of C-N and N-C = O, respectively, indicate the presence of DAA; the presence of MAA monomer is evidenced by the 288.57 eV characteristic band of the carboxyl group. In addition, the O1s spectrum of MAA-co-DAA-co-PEGMA is reversely analyzed at 531.27, 532.69 and 533.28 eV into 3 wave bands, which are respectively assigned to the carbonyl, ether and carboxyl structures of the surface structure of MAA-co-DAA-co-PEGMA, and further illustrate the existence of the monomers. Based on the above results, the successful synthesis of the copolymer MAA-co-DAA-co-PEGMA was demonstrated.
Example 2
The difference from example 1 is that: in step (2), the amount of TBDMS-DAA was kept constant, and the amount of MAA was adjusted in accordance with the molar equivalent ratio of MAA to TBDMS-DAA of 32: 2, otherwise the same as in example 1.
Example 3
The difference from example 1 is that: in step (2), the amount of MAA was adjusted by keeping the amount of TBDMS-DAA constant and the molar equivalent ratio of MAA to TBDMS-DAA was 8: 2, as in example 1.
Example 4
The difference from example 1 is that: in step (2), PEGMA has a molecular weight of 900, and the rest is the same as in example 1.
Example 5
The difference from example 1 is that: in the step (2), the reaction temperature was 60 ℃ and the same was applied to the same reaction in example 1.
Example 6
The difference from example 1 is that: in the step (2), the reaction time was 10 hours, and the rest was the same as in example 1.
And (3) stability testing:
the mean hydrodynamic diameter of 0.5 mg/mL MAA-co-DAA-co-PEGMA copolymer (prepared in example 1) in PBS buffer at pH 7.4, PBS (pH 7.4) + DMEM mixed solution (volume ratio, PBS: DMEM = 1: 9) was followed using DLS for 6 consecutive days, and the results are shown in fig. 5, showing: the MAA-co-DAA-co-PEGMA copolymer has good stability in the range of test time.
Drug loading and sustained release study:
carrying out drug loading: 90 mg of MAA-co-DAA-co-PEGMA copolymer solid powder prepared in example 1 was ultrasonically dispersed uniformly in 81 mL of NaOH solution with pH 8.5; 90 mg of Bortezomib (BTZ) is dissolved in 9 mL of dimethyl sulfoxide, the solution is dripped into the ultrasonic solution, the pH is adjusted to 8.5 by NaOH solution with the pH of 9.0 again, the solution is adsorbed for 24 hours in a dark place, the solution is centrifugally separated and washed with water for three times, namely, the bortezomib is loaded on the MAA-co-DAA-co-PEGMA copolymer, and the mark is the MAA-co-DAA-co-PEGMA copolymer @ BTZ. 5 mg of MAA-co-DAA-co-PEGMA copolymer @ BTZ was dissolved in 10 mL of PBS solution with pH 7.4, and the copolymer and its Zeta potential after loading with drug were tested separately using MAA-co-DAA-co-PEGMA copolymer (i.e., no drug loading) as a control, and the Bortezomib loading was tested by UV, as shown in tables 1 and 2, respectively, showing that: the MAA-co-DAA-co-PEGMA copolymer shows higher electronegativity of-36.75 mV in PBS buffer solution with the pH value of 7.4, and the electronegativity is weakened after the surface is loaded with a positively charged medicament, thereby proving the successful connection of the BTZ on the surface of the MAA-co-DAA-co-PEGMA copolymer.
In order to simulate the release behavior of the drug under the environment of human body fluid, the in vitro drug slow release is carried out under the PBS buffer solution with pH 7.4, pH 5.0, pH 7.4 containing 10 mM Glutathione (GSH) and pH 5.0 containing 10 mM Glutathione (GSH), and the method specifically comprises the following steps: the MAA-co-DAA-co-PEGMA copolymer @ BTZ obtained in item "(one) drug load" was transferred into a dialysis bag having a molecular weight cut-off of 3500, placed in 150 mL of each PBS buffer solution (pH 7.4, pH 5.0, pH 7.4 containing 10 mM GSH and pH 5.0 containing 10 mM GSH), and sampled at a predetermined time point, followed by measuring the cumulative amount of released drug using an ultraviolet spectrophotometer.
The sustained drug release profile of MAA-co-DAA-co-PEGMA copolymer @ BTZ is shown in FIG. 6, and it can be seen from FIG. 6 that: the sustained release of the drug in vitro is carried out under PBS buffer solution containing 10 mM GSH at pH 7.4, 10 mM GSH at pH 5.0 and 10 mM GSH at pH 5.0, and the cumulative release amounts of the drug are 3.31%, 6.11%, 23.07% and 51.19%, respectively, which proves that the structure has dual stimulation responsiveness of pH and oxidation reduction and can be used for treating tumors.
Claims (4)
1. MAA-co-DAA-co-PEGMA copolymer characterized by the structural formula:
wherein a, b, c and d are positive integers, and a: b: c: d = (1-32): 1: 2.
2. The MAA of claim 1-co-DAA-co-A process for the preparation of PEGMA copolymers, characterized in that:
(1) respectively dissolving TBDMS-DAA and BACy in DMF to obtain TBDMS-DAA solution and BACy solution; dissolving TBAF in THF to obtain a TBAF solution;
(2) adding MAA, TBDMS-DAA solution, PEGMA, BACy solution and SDS into water in nitrogen atmosphere, mixing, heating to 40-100 ℃ under stirring, adding APS, reacting for 5-10 h, centrifuging, washing, and freeze-drying;
(3) adding the product obtained in the step (2) into TBAF solution, stirring, centrifugally collecting precipitate, washing with THF, washing with water and freeze-drying to obtain MAA -co-DAA-co-PEGMA copolymers;
in the step (2), the molar ratio of MAA, BACy, PEGMA and TBDMS-DAA is (1-32) to 1: 2, the total input amount of APS is (1-3)/1000 of the total mass of MAA, PEGMA and TBDMS-DAA, and the consumption of water is 10-15 times of the total volume of the TBDMS-DAA solution and the BACy solution; the concentration of SDS in the mixed solution of the step (2) is 1.5-2.0 g/L;
in the step (3), the amount of TBAF is 3-10 times of the amount of TBDMS-DAA added in the step (2) by mol.
3. The MAA of claim 2-co-DAA-co-A process for the preparation of PEGMA copolymers, characterized in that:
in the step (1), the concentration of the TBDMS-DAA solution is 90-270 mg/mL, the concentration of the BACy solution is 50-170 mg/mL, and the concentration of the TBAF solution is 0.1-0.4 mol/L.
4. The MAA of claim 1-co-DAA-co-Use of a PEGMA copolymer in the preparation of a pharmaceutical carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911016536.1A CN110591016B (en) | 2019-10-24 | 2019-10-24 | MAA-co-DAA-co-PEGMA copolymer and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911016536.1A CN110591016B (en) | 2019-10-24 | 2019-10-24 | MAA-co-DAA-co-PEGMA copolymer and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110591016A CN110591016A (en) | 2019-12-20 |
| CN110591016B true CN110591016B (en) | 2022-07-29 |
Family
ID=68850239
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911016536.1A Active CN110591016B (en) | 2019-10-24 | 2019-10-24 | MAA-co-DAA-co-PEGMA copolymer and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110591016B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107686541A (en) * | 2017-07-19 | 2018-02-13 | 华东理工大学 | Three DOPA amine compounds and polymer and preparation method and application |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11015010B2 (en) * | 2014-02-28 | 2021-05-25 | Japan Science And Technology Agency | Block copolymer comprising catechol segment and inorganic nanoparticles coated by said block copolymer, as well as method for producing block copolymer comprising catechol segment and method for producing inorganic nanoparticles coated by said block copolymer |
-
2019
- 2019-10-24 CN CN201911016536.1A patent/CN110591016B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107686541A (en) * | 2017-07-19 | 2018-02-13 | 华东理工大学 | Three DOPA amine compounds and polymer and preparation method and application |
Non-Patent Citations (3)
| Title |
|---|
| "Catechol-Functionalized Synthetic Polymer as a Dental Adhesive to Contaminated Dentin Surface for a Composite Restoration";Sang-Bae Lee等;《Biomacromolecules》;20150715(第16期);第2265-2275页 * |
| "含儿茶酚基团聚合物胶束对硼替佐米的控制释放研究";杨柳;《中国优秀硕士学位论文全文数据库（硕士） 医药卫生科技辑》;20170315(第3期);第11-15页 * |
| Novel fluorescent pH/reduction dual stimuli-responsive polymeric nanoparticles for intracellular triggered anticancer drug release;Xu Jia等;《Chemical Engineering Journal》;20160319(第295期);第468-476页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110591016A (en) | 2019-12-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | pH-Controlled drug delivery with hybrid aerogel of chitosan, carboxymethyl cellulose and graphene oxide as the carrier | |
| Fathi et al. | Methotrexate-conjugated chitosan-grafted pH-and thermo-responsive magnetic nanoparticles for targeted therapy of ovarian cancer | |
| Ouyang et al. | Multifunctional hydrogels based on chitosan, hyaluronic acid and other biological macromolecules for the treatment of inflammatory bowel disease: A review | |
| Hua et al. | Magnetic-nanoparticle-modified paclitaxel for targeted therapy for prostate cancer | |
| Prabha et al. | Preparation and characterization of chitosan—Polyethylene glycol‐polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles as carrier system: Drug loading and in vitro drug release study | |
| Kumar et al. | Ciprofloxacin loaded genipin cross-linked chitosan/heparin nanoparticles for drug delivery application | |
| Maiti et al. | Development of a thermosensitive protein conjugated nanogel for enhanced radio-chemotherapy of cancer | |
| CN112546027B (en) | Fat-soluble pigment-loaded nanoparticle and preparation method thereof | |
| Nan et al. | Polymeric hydrogel nanocapsules: A thermo and pH dual-responsive carrier for sustained drug release | |
| Li et al. | Efficient fabrication of reversible pH-induced carboxymethyl chitosan nanoparticles for antitumor drug delivery under weakly acidic microenvironment | |
| CN105131182B (en) | Poly- (β amino esters) polymer of pluronic and its synthesis and methods for using them | |
| Li et al. | GSH and light dual stimuli-responsive supramolecular polymer drug carriers for cancer therapy | |
| Hanna et al. | Synthesis and characterization of poly (3-hydroxybutyrate)/chitosan-graft poly (acrylic acid) conjugate hyaluronate for targeted delivery of methotrexate drug to colon cancer cells | |
| CN113457587A (en) | Multiple-response core-shell structure nanogel and preparation method and application thereof | |
| Yang et al. | Delivery of doxorubicin by dual responsive carboxymethyl chitosan based nanogel and in vitro performance | |
| CN108096214B (en) | Magnetotactic bacteria quantum dot microcapsule and preparation method thereof | |
| Kumar et al. | Redox-sensitive nanoparticles based on xylan-lipoic acid conjugate for tumor targeted drug delivery of niclosamide in cancer therapy | |
| Zhu et al. | Redox and pH dual sensitive carboxymethyl chitosan functionalized polydopamine nanoparticles loaded with doxorubicin for tumor chemo-photothermal therapy | |
| CN110790922B (en) | Preparation method and application of polyporphyrin compound | |
| CN111249253B (en) | Preparation method of core-shell structure stimulus response type drug carrier and drug release method | |
| Geyik et al. | Multi-stimuli-sensitive superparamagnetic κ-carrageenan based nanoparticles for controlled 5-fluorouracil delivery | |
| CN110804178B (en) | Nano drug-loaded system with glutathione responsiveness and preparation method and application thereof | |
| CN107224590B (en) | Degradable polymer magnetic nano particle and preparation method thereof | |
| CN111870579A (en) | Tumor-targeted nano micelle, preparation method and application of nano micelle as drug carrier | |
| CN107802834B (en) | Manganese-zinc ferrite targeted nano composite carrier and preparation method thereof |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |