CN117487095A - Method for preparing gelatin polyelectrolyte brush by photoinitiated emulsion polymerization method - Google Patents
Method for preparing gelatin polyelectrolyte brush by photoinitiated emulsion polymerization method Download PDFInfo
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- CN117487095A CN117487095A CN202311146996.2A CN202311146996A CN117487095A CN 117487095 A CN117487095 A CN 117487095A CN 202311146996 A CN202311146996 A CN 202311146996A CN 117487095 A CN117487095 A CN 117487095A
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- 229920000867 polyelectrolyte Polymers 0.000 title claims abstract description 118
- 229920000159 gelatin Polymers 0.000 title claims abstract description 105
- 235000019322 gelatine Nutrition 0.000 title claims abstract description 105
- 108010010803 Gelatin Proteins 0.000 title claims abstract description 103
- 239000008273 gelatin Substances 0.000 title claims abstract description 103
- 235000011852 gelatine desserts Nutrition 0.000 title claims abstract description 103
- 238000000034 method Methods 0.000 title claims abstract description 38
- 238000010556 emulsion polymerization method Methods 0.000 title claims abstract description 11
- 239000000178 monomer Substances 0.000 claims abstract description 63
- 239000002105 nanoparticle Substances 0.000 claims abstract description 49
- 238000002156 mixing Methods 0.000 claims abstract description 24
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical class CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 13
- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000035484 reaction time Effects 0.000 claims abstract description 4
- 230000000977 initiatory effect Effects 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 230000001105 regulatory effect Effects 0.000 claims description 29
- 238000007720 emulsion polymerization reaction Methods 0.000 claims description 20
- 238000000502 dialysis Methods 0.000 claims description 19
- 238000004108 freeze drying Methods 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- XHZPRMZZQOIPDS-UHFFFAOYSA-N 2-Methyl-2-[(1-oxo-2-propenyl)amino]-1-propanesulfonic acid Chemical compound OS(=O)(=O)CC(C)(C)NC(=O)C=C XHZPRMZZQOIPDS-UHFFFAOYSA-N 0.000 claims description 10
- 229920000536 2-Acrylamido-2-methylpropane sulfonic acid Polymers 0.000 claims description 9
- 125000005395 methacrylic acid group Chemical group 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 6
- 229920001448 anionic polyelectrolyte Polymers 0.000 claims description 6
- 125000002091 cationic group Chemical group 0.000 claims description 6
- 230000007935 neutral effect Effects 0.000 claims description 6
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 5
- ZSZRUEAFVQITHH-UHFFFAOYSA-N 2-(2-methylprop-2-enoyloxy)ethyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CC(=C)C(=O)OCCOP([O-])(=O)OCC[N+](C)(C)C ZSZRUEAFVQITHH-UHFFFAOYSA-N 0.000 claims description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 5
- 239000007853 buffer solution Substances 0.000 claims description 5
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 claims description 5
- RRHXZLALVWBDKH-UHFFFAOYSA-M trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CC(=C)C(=O)OCC[N+](C)(C)C RRHXZLALVWBDKH-UHFFFAOYSA-M 0.000 claims description 5
- 239000003431 cross linking reagent Substances 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 3
- BCAIDFOKQCVACE-UHFFFAOYSA-N 3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate Chemical compound CC(=C)C(=O)OCC[N+](C)(C)CCCS([O-])(=O)=O BCAIDFOKQCVACE-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 230000004048 modification Effects 0.000 claims description 3
- 238000012986 modification Methods 0.000 claims description 3
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- XFTALRAZSCGSKN-UHFFFAOYSA-M sodium;4-ethenylbenzenesulfonate Chemical compound [Na+].[O-]S(=O)(=O)C1=CC=C(C=C)C=C1 XFTALRAZSCGSKN-UHFFFAOYSA-M 0.000 claims description 3
- FZGFBJMPSHGTRQ-UHFFFAOYSA-M trimethyl(2-prop-2-enoyloxyethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CCOC(=O)C=C FZGFBJMPSHGTRQ-UHFFFAOYSA-M 0.000 claims description 3
- XMLYCEVDHLAQEL-UHFFFAOYSA-N 2-hydroxy-2-methyl-1-phenylpropan-1-one Chemical compound CC(C)(O)C(=O)C1=CC=CC=C1 XMLYCEVDHLAQEL-UHFFFAOYSA-N 0.000 claims description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 2
- 238000004807 desolvation Methods 0.000 claims description 2
- -1 methacrylic acid anhydride modified methacrylic acid Chemical class 0.000 claims description 2
- POECFFCNUXZPJT-UHFFFAOYSA-M sodium;carbonic acid;hydrogen carbonate Chemical compound [Na+].OC(O)=O.OC([O-])=O POECFFCNUXZPJT-UHFFFAOYSA-M 0.000 claims description 2
- 239000001828 Gelatine Substances 0.000 claims 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
- 239000000047 product Substances 0.000 description 20
- 229910052757 nitrogen Inorganic materials 0.000 description 19
- 238000005086 pumping Methods 0.000 description 16
- 238000005303 weighing Methods 0.000 description 16
- 239000008367 deionised water Substances 0.000 description 10
- 229910021641 deionized water Inorganic materials 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000002245 particle Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 229960000789 guanidine hydrochloride Drugs 0.000 description 3
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 3
- 238000005286 illumination Methods 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- CLSIFQGHPQDTHQ-DTWKUNHWSA-N (2s,3r)-2-[(4-carboxyphenyl)methyl]-3-hydroxybutanedioic acid Chemical compound OC(=O)[C@H](O)[C@@H](C(O)=O)CC1=CC=C(C(O)=O)C=C1 CLSIFQGHPQDTHQ-DTWKUNHWSA-N 0.000 description 2
- 238000002296 dynamic light scattering Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 230000003472 neutralizing effect Effects 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 239000005062 Polybutadiene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- HDFXRQJQZBPDLF-UHFFFAOYSA-L disodium hydrogen carbonate Chemical compound [Na+].[Na+].OC([O-])=O.OC([O-])=O HDFXRQJQZBPDLF-UHFFFAOYSA-L 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229920001002 functional polymer Polymers 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920002553 poly(2-methacrylolyloxyethyltrimethylammonium chloride) polymer Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920002946 poly[2-(methacryloxy)ethyl phosphorylcholine] polymer Polymers 0.000 description 1
- 229920002857 polybutadiene Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Classifications
-
- 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
- C08F289/00—Macromolecular compounds obtained by polymerising monomers on to macromolecular compounds not provided for in groups C08F251/00 - C08F287/00
-
- 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
- C08F2/00—Processes of polymerisation
- C08F2/46—Polymerisation initiated by wave energy or particle radiation
- C08F2/48—Polymerisation initiated by wave energy or particle radiation by ultraviolet or visible light
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Polymerisation Methods In General (AREA)
- Graft Or Block Polymers (AREA)
Abstract
The invention provides a method for preparing a gelatin polyelectrolyte brush by a photoinitiated emulsion polymerization method, which comprises the steps of grafting a photoinitiator HMEM on the surface of methacrylic acid anhydride surface modified methacrylic acid gelatin nano particles, mixing the surface modified methacrylic acid gelatin nano particles with polyelectrolyte monomers, and carrying out ultraviolet light irradiation initiation polymerization reaction, wherein the polyelectrolyte monomers are grafted on the surface of a gelatin sphere core under the action of the photoinitiator HMEM to form a slender molecular chain, and finally, a structure similar to a brush is formed, so that the gelatin spherical polyelectrolyte brush is obtained. The gelatin spherical polyelectrolyte brush prepared by the invention has regular appearance and uniform size, and the thickness of the brush layer of the gelatin spherical polyelectrolyte brush can be adjusted by changing the monomer amount, the reaction time, the ionic strength and the pH value, so that the gelatin spherical polyelectrolyte brush has wide application prospect in the field of biological medicines.
Description
Technical Field
The invention relates to the field of preparation of functional polymer materials, in particular to a method for preparing a gelatin polyelectrolyte brush by a photoinitiated emulsion polymerization method and the gelatin polyelectrolyte brush prepared by the method.
Background
The nano spherical polyelectrolyte brush (Spherical Polyelectrolyte Brush, SPB) refers to a macromolecular assembled structure formed by connecting polyelectrolyte chains on the surfaces of nano spherical particles with certain grafting density, and the traditional material for synthesizing the SPB sphere core (such as polystyrene, polybutadiene and the like) has potential problems in terms of biodegradation, so that the application of the SPB in the biomedical field is limited.
Gelatin is used as a natural polymer material, has good biocompatibility, biodegradability, no immunogenicity and blood compatibility, takes gelatin as a core of the nano spherical polyelectrolyte brush, combines the unique properties of excellent stability, biological lubricity, wettability and the like of the nano spherical polyelectrolyte brush, and can be widely applied to the biomedical fields such as tissue engineering, drug delivery systems, immunodiagnosis and the like. The photo-initiated emulsion polymerization has the advantages of fast reaction rate, high selectivity, controllable structure, no need of toxic catalyst, mild reaction condition, etc.
Therefore, how to combine the photoinitiation technology provides a preparation method of the polyelectrolyte brush with milder preparation conditions, higher efficiency and good biocompatibility, which has very positive significance.
Disclosure of Invention
The invention provides a method for preparing a gelatin spherical polyelectrolyte brush by a photoinitiated emulsion polymerization method, which can prepare the gelatin spherical polyelectrolyte brush with uniform particle size and good biocompatibility.
In order to achieve the above purpose, the technical scheme of the invention is as follows: the method for preparing the gelatin polyelectrolyte brush by the photoinitiated emulsion polymerization method comprises the steps of mixing methacrylic acid gelatin nano particles with surface grafted with a photoinitiator with polyelectrolyte monomers, regulating the pH value of a reaction system, and then performing ultraviolet light initiation polymerization reaction in an anaerobic environment to prepare the gelatin spherical polyelectrolyte brush; wherein the polyelectrolyte monomer is selected from any one of an anionic polyelectrolyte monomer, a cationic polyelectrolyte monomer, a zwitterionic polyelectrolyte monomer or a neutral polyelectrolyte monomer;
when the polyelectrolyte monomer is an anionic polyelectrolyte monomer or a cationic polyelectrolyte monomer, regulating the pH of a reaction system until the methacrylic gelatin nano particles of the surface grafting photoinitiator and the polyelectrolyte monomer have opposite charges; when the polyelectrolyte monomer is a zwitterionic polyelectrolyte monomer or a neutral polyelectrolyte monomer, regulating the pH of a reaction system to the isoelectric point of the methacrylic acid gelatin nanoparticle of the surface grafting photoinitiator.
When the reaction system is subjected to polymerization reaction, the polyelectrolyte monomer can be grafted on the surface of the gelatin spherical core under the action of a photoinitiator to form an elongated molecular chain, and finally a brush-like structure is formed, so that the gelatin spherical polyelectrolyte brush is prepared.
It is further preferred that the anionic polyelectrolyte monomers include acrylic acid, sodium p-styrenesulfonate, 2-acrylamido-2-methylpropanesulfonic Acid (AMPS).
It is further preferred that the cationic polyelectrolyte monomer comprises methacryloyloxyethyl trimethyl ammonium chloride, 2-aminoethyl ester hydrochloride, and acryloyloxyethyl trimethyl ammonium chloride.
It is further preferred that the zwitterionic polyelectrolyte monomer comprises [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide, 3- [ [2- (methylendoyloxy) yl ] dimethylamino ] inner acid inner salt, 2-methacryloyloxyethyl phosphorylcholine.
It is further preferred that the neutral polyelectrolyte monomers include methacrylates, styrene, N-isopropylacrylamide.
It is further preferred in the present invention that the photoinitiator is 2- [ p- (2-hydroxy-2-methylpropionyl) ethylene glycol-acrylate (HMEM), and the structural formula of the photoinitiator HMEM is as follows:
the invention further preferably comprises the following components in percentage by mass (1-15): 1.
in the present invention, it is further preferable that the reaction time of the polymerization reaction is 2 to 3 hours.
It is further preferred that the chain length of the prepared gelatin spherical polyelectrolyte brush is 10-400nm.
The invention further preferably provides a preparation method of the gelatin spherical polyelectrolyte brush, which comprises the following steps:
s1: gelatin is taken as a raw material, a desolvation method is adopted, and a cross-linking agent is added to enable the gelatin to self-assemble to form gelatin nano particles;
s2: surface modification is carried out on the prepared gelatin nano particles by using methacrylic anhydride to prepare methacrylic acid gelatin nano particles;
s3: grafting the photoinitiator HMEM on the surface of the methacrylic acid gelatin nanoparticle;
s4: the methacrylic acid gelatin nano particles grafted with the photoinitiator on the grafted surface are mixed with polyelectrolyte monomers, the pH value of a reaction system is regulated, and then polymerization reaction is carried out under ultraviolet irradiation.
It is further preferred that in step S4, the pH of the reaction system is adjusted by experimental NaOH or HCl solution.
In a further preferred aspect of the present invention, in step S1, the preparation of the gelatin nanoparticle includes the following steps:
(1) Mixing gelatin and deionized water, stirring and dissolving, adding concentrated hydrochloric acid, and regulating the pH value of the system to 1-3;
(2) Adding excessive acetone into the reaction system until the turbidity of the reaction system is greatly increased, so that the long chain of the gelatin molecule is curled to form self-assembled nano particles;
(3) Adding a cross-linking agent glutaraldehyde solution to crosslink and solidify gelatin particles;
(4) Adding guanidine hydrochloride solution, neutralizing glutaraldehyde remained in the reaction system, stopping the crosslinking reaction, centrifuging the solution, purifying, and freeze-drying to obtain the self-assembled gelatin nanoparticle.
In a further preferred aspect of the present invention, in step S2, the preparation of the methacrylic acid gelatin nanoparticle includes the following steps:
(1) Mixing, stirring and dissolving the gelatin nano particles and carbonic acid-sodium bicarbonate buffer solution (CB buffer solution), and adjusting the pH value to be 8-10;
(2) Adding a certain amount of methacrylic anhydride, and carrying out light-proof reaction at 50-55 ℃;
(3) After the light-shielding reaction is finished, dialyzing and purifying the product in hot water, wherein the molecular weight cut-off of a dialysis bag is 8-14kDa;
(4) And freeze-drying the purified solution to obtain the required methacrylic gelatin nano-particles.
In the step S3, the methacrylic acid anhydride modified methacrylic acid gelatin nano particles and the photoinitiator HMEM are mixed in a nitrogen atmosphere and reacted for 2-3 hours at 70-90 ℃ to obtain the surface grafted photoinitiator methacrylic acid gelatin nano particles.
In step S4, the polyelectrolyte monomer is dissolved in deionized water, then added into a reaction device together with the methacrylic acid gelatin nanoparticles grafted with the photoinitiator on the surface, the pH value of the solution is regulated, nitrogen is pumped, ultraviolet light irradiation is carried out under stirring to initiate polymerization reaction, after 2-3 hours of reaction, illumination is stopped, and a dialysis bag is used for dialyzing the reaction product in deionized water, so that the gelatin spherical polyelectrolyte brush is prepared.
The invention further preferably provides a preparation method of the gelatin spherical polyelectrolyte brush, which comprises the following steps:
s1: adding gelatin and deionized water into a three-neck flask, stirring and dissolving at 35-50 ℃, then dripping concentrated hydrochloric acid, and regulating the pH value of the system to 1-3;
s2: adding a large amount of acetone to curl long chains of gelatin molecules to form self-assembled nano particles;
s3: adding a cross-linking agent glutaraldehyde to crosslink and solidify the gelatin particles;
s4: adding guanidine hydrochloride solution, neutralizing glutaraldehyde remained in the system, stopping the crosslinking reaction, and centrifugally purifying the product to obtain gelatin nano particles;
s5: mixing gelatin nanoparticles, CB buffer solution and additional deionized water in a flask to enable the concentration of the gelatin nanoparticles to reach 1-3wt% and fully stirring at 45-55deg.C;
s5: adding Methacrylic Anhydride (MA) into the mixed system, reacting for 1.0-2.0h under the magnetic stirring of 500-700rpm, and dialyzing and purifying by deionized water after the reaction is finished to obtain methacrylic anhydride modified gelatin nano particles;
s6: mixing the prepared methacrylic acid gelatin nano particles (Gel-MA) with a photoinitiator HMEM in a nitrogen atmosphere in a flask, and reacting for 2-3 hours at 75-85 ℃ to obtain Gel-HMEM;
s7: after polyelectrolyte monomer is dissolved in deionized water, the polyelectrolyte monomer and Gel-HMEM are added into a flask together, and the pH value of the solution is regulated by NaOH or HCl;
and S8, pumping nitrogen, reacting for 2-3 hours under the condition of ultraviolet light illumination under the magnetic stirring of 750-850rpm, and dialyzing in deionized water by using a dialysis bag to obtain the gelatin spherical polyelectrolyte brush.
The invention also provides a gelatin spherical polyelectrolyte brush prepared by the method for preparing a gelatin polyelectrolyte brush according to any one of the above.
Compared with the prior art, the invention has the following beneficial effects:
(1) The invention adopts a photoinitiated emulsion polymerization method, belongs to a surface grafting method, has higher surface grafting density, can regulate grafting density by the addition of a photoinitiator, and can adjust the thickness of a brush layer of the gelatin spherical polyelectrolyte brush by changing the amount of monomers, the reaction time, the ionic strength and the pH value.
(2) The novel gelatin spherical polyelectrolyte brush is successfully synthesized by photoinitiated polymerization, the material has controllable polyelectrolyte chain length, toxic substances which are difficult to remove are not introduced in the preparation process, and the material has good biocompatibility, so that the material has wide application prospect in biomedical application.
(3) In the preparation process, methacrylic anhydride is used as a surface modifying reagent, 2- [ para- (2-hydroxy-2-methyl propiophenone) ] -glycol-acrylic ester (HMEM) is used as a photoinitiator, a photoinitiated emulsion polymerization method is adopted to prepare the gelatin spherical polyelectrolyte brush, the repeatability is good, the experimental condition is mild, the process is carried out at normal temperature, the required time is shorter, and the product is regular in appearance and uniform in particle size.
Drawings
FIG. 1 is a flowchart of the preparation of the gelatin spherical polyelectrolyte brush according to the present invention.
FIG. 2 is an SEM image of gelatin nanoparticles (Gel-NPs) prepared in example 1.
FIG. 3 is a graph showing the particle size distribution of gelatin nanoparticles before grafting of monomer to the gelatin spherical polyelectrolyte brush prepared in example 1.
FIG. 4 is an infrared spectrum of Gel-PAMPS, AMPS monomer, gel-MA grafted photoinitiator, gel-HMEM, MA modified gelatin nanoparticle Gel-MA, and crosslinked gelatin nanoparticle Gel-NPs of the Gel-spherical polyelectrolyte brush prepared in example 1.
Detailed Description
The invention is further illustrated by the following examples. The following examples are only illustrative of the present invention and are not intended to limit the scope of the invention.
The raw materials in the invention can be directly purchased. In the embodiment of the invention, dynamic light scattering instrument, SEM (scanning electron microscope) and infrared spectrum are adopted to characterize the product in the preparation process.
Chain length of the spherical polyelectrolyte brush in the present invention= (D) (Gel-PAMPS) -D (Gel-NPs) )/2。
Example 1
In this example, as shown in fig. 1, gelatin nanoparticles, methacrylic gelatin nanoparticles, and methacrylic gelatin nanoparticles with a surface grafted with a photoinitiator were prepared in order from gelatin as a raw material, and finally a gelatin spherical polyelectrolyte brush was prepared by a photoinitiated emulsion polymerization method.
The preparation of the gelatin spherical polyelectrolyte brush specifically comprises the following steps: weighing 5g of gelatin and 60mL of deionized water, putting into a three-neck flask, stirring and dissolving at 40 ℃, dripping concentrated hydrochloric acid, regulating the pH value of the system to 1-3, and then adding excessive acetone to greatly increase the turbidity of the reaction system; then adding 600 mu L of glutaraldehyde solution, carrying out crosslinking reaction overnight, adding 100mL of 100mM guanidine hydrochloride aqueous solution, stirring and reacting for 1-2h, centrifuging and purifying, and freeze-drying to obtain gelatin nanoparticles (Gel-NPs), and adopting an SEM (scanning electron microscope) to characterize the morphology of the gelatin nanoparticles, as shown in figure 2;
1g of Gel-NPs is weighed and dissolved in 100mL of sodium carbonate-sodium bicarbonate buffer solution with the concentration of 1M, after the pH is regulated to 9, 1-1.5mL of methacrylic anhydride is added, after the reaction is carried out for 1h at 50-55 ℃ in the dark, the product is dialyzed and purified, and then Gel-MA is obtained; weighing 100mL of Gel-MA, adding into a three-neck flask, pumping nitrogen for 5 times, placing into an oil bath pan, stirring at 80 ℃, injecting 200mg of HMEM into the flask by using a needle cylinder, and reacting for 2-3 hours to obtain methacrylic gelatin nano particles (Gel-HMEM) with the surface grafted with a photoinitiator;
100mg of AMPS is weighed and dissolved in deionized water, then the mixture and 20mg of Gel-HMEM are added into a flask together for mixing, the pH value of the solution is regulated to be alkaline by NaOH, the Gel-HMEM and the polyelectrolyte monomer are charged oppositely, nitrogen is pumped for 5 times, photoinitiated polymerization reaction is carried out under the magnetic stirring of 800rpm and the illumination of an ultraviolet lamp, after the reaction is carried out for 2-3 hours, the product is dialyzed and purified by a dialysis bag, and the purified solution is freeze-dried, so that the required spherical polyelectrolyte brush Gel-PAMPS can be prepared. In the preparation process, a dynamic light scattering instrument is adopted to detect the particle size distribution of the reaction product, and infrared characterization is carried out on the reaction product in each process, wherein the particle size distribution and the infrared spectrogram result are shown in fig. 3 and 4. The chain length of the obtained spherical polyelectrolyte brush was 200nm.
Example 2
The difference from example 1 is that the polyelectrolyte monomer selected is Acrylic Acid (AA). The procedure for photoinitiated emulsion polymerization was as follows: weighing 20mg of Gel-HMEM and 100mg of AA, mixing, regulating the pH of the solution to be alkaline, pumping nitrogen for 5 times, carrying out ultraviolet light irradiation reaction for 2-3 hours, dialyzing and purifying the product by using a dialysis bag, and freeze-drying the purified solution to obtain Gel-PAA, wherein the chain length of the obtained spherical polyelectrolyte brush is 190nm.
Example 3
The difference from example 1 is that the polyelectrolyte monomer selected is sodium p-styrenesulfonate (SS). The procedure for photoinitiated emulsion polymerization was as follows: weighing 20mg of Gel-HMEM and 100mg of SS, mixing, regulating the pH of the solution to be alkaline, pumping nitrogen for 5 times, carrying out ultraviolet light irradiation reaction for 2.5 hours, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PSS, wherein the chain length of the obtained spherical polyelectrolyte brush is 195nm.
Example 4
The difference from example 1 is that the polyelectrolyte monomer selected is methacryloyloxyethyl trimethyl ammonium chloride (METAC), and the pH of the solution before polymerization is adjusted to be acidic, causing Gel-HMEM to be oppositely charged to the polyelectrolyte monomer. The procedure for photoinitiated emulsion polymerization was as follows: weighing 20mg of Gel-HMEM and 100mg of METAC, mixing, regulating the pH of the solution to be acidic, pumping nitrogen for 5 times, reacting for 2.5 hours by ultraviolet light, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PMETAC, wherein the chain length of the obtained spherical polyelectrolyte brush is 150nm.
Example 5
The difference from example 4 is that the polyelectrolyte monomer selected is 2-aminoethyl ester hydrochloride (AMA), and the procedure for photoinitiated emulsion polymerization is as follows: weighing 20mg of Gel-HMEM and 100mg of AMA, mixing, regulating the pH of the solution to be acidic, pumping nitrogen for 5 times, reacting for 2-3 hours by ultraviolet light, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PAMA, wherein the chain length of the obtained spherical polyelectrolyte brush is 144nm.
Example 6
The difference from example 4 is that the polyelectrolyte monomer selected is acryloxyethyl trimethyl ammonium chloride (DMC), and the photoinitiated emulsion polymerization is carried out as follows: weighing 20mg of Gel-HMEM and 100mg of DMC, mixing, regulating the pH of the solution to be acidic, pumping nitrogen for 5 times, then carrying out ultraviolet light reaction for 2-3 hours, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain the Gel-PDMC, wherein the chain length of the obtained spherical polyelectrolyte brush is 154nm.
Example 7
The difference from example 1 is that the polyelectrolyte monomer selected was [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide (SBMA), and the pH of the solution before polymerization was adjusted to 4 to 5 to Gel-HMEM isoelectric point, and the procedure for photoinitiated emulsion polymerization was as follows: weighing 20mg of Gel-HMEM and 100mg of SBMA, mixing, regulating the pH of the solution to 4-5, pumping nitrogen for 5 times, performing ultraviolet light irradiation reaction for 2-3h, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PSBMA, wherein the chain length of the obtained spherical polyelectrolyte brush is 250nm.
Example 8
The difference from example 7 is that the polyelectrolyte monomer selected is 3- [ [2- (methylendocyloxy) group ] dimethylamino ] inner acid inner salt (CBMA), and the process of photoinitiated emulsion polymerization is as follows: weighing 20mg of Gel-HMEM and 100mg of CBMA, mixing, regulating the pH of the solution to 4-5, pumping nitrogen for 5 times, performing ultraviolet light irradiation reaction for 2-3h, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PCBMA, wherein the chain length of the obtained spherical polyelectrolyte brush is 252nm.
Example 9
The difference from example 7 is that the polyelectrolyte monomer selected is 2-Methacryloyloxyethyl Phosphorylcholine (MPC), and the procedure for photoinitiated emulsion polymerization is as follows: weighing 20mg of Gel-HMEM and 100mg of MPC, mixing, regulating the pH of the solution to 4-5, pumping nitrogen for 5 times, performing ultraviolet light irradiation reaction for 2-3h, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PMPC, wherein the chain length of the obtained spherical polyelectrolyte brush is 253nm.
Example 10
The difference from example 1 is that the polyelectrolyte monomer selected is methacrylate (MMA), the pH of the solution is adjusted to 4-5 before the reaction to Gel-HMEM isoelectric point, and the photo-induced emulsion polymerization reaction is carried out as follows: weighing 20mg of Gel-HMEM and 100mg of MMA, mixing, regulating the pH of the solution to 4-5, pumping nitrogen for 5 times, performing ultraviolet light irradiation reaction for 2-3h, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PMMA, wherein the chain length of the obtained spherical polyelectrolyte brush is 200nm.
Example 11
The difference from example 10 is that the polyelectrolyte monomer selected is styrene (PS), and the procedure for photoinitiated emulsion polymerization is as follows: weighing 20mg of Gel-HMEM and 100mg of PS, mixing, regulating the pH of the solution to 4-5, pumping nitrogen for 5 times, performing ultraviolet light irradiation reaction for 2-3h, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PPS, wherein the chain length of the obtained spherical polyelectrolyte brush is 195nm.
Example 12
The difference from example 10 is that the polyelectrolyte monomer selected is N-isopropylacrylamide (NIPAM), and the procedure for photoinitiated emulsion polymerization is as follows: weighing 20mg of Gel-HMEM and 100mg of NIPAM, mixing, regulating the pH of the solution to 4-5, pumping nitrogen for 5 times, performing ultraviolet light irradiation reaction for 2-3h, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PNIPAM, wherein the chain length of the obtained spherical polyelectrolyte brush is 194nm.
Example 13
The difference from example 1 is that the pH value of the solution is not adjusted before photoinitiated emulsion polymerization, the pH value of the solution is kept acidic after mixing, the solution is pumped with nitrogen for 5 times and then subjected to irradiation reaction for 2-3 hours by ultraviolet light, and the spherical polyelectrolyte brush can not be obtained after reaction precipitation.
Example 14
The difference from example 1 is that the addition amount of AMPS monomer is different and the procedure for photoinitiated emulsion polymerization is as follows: weighing 20mg of Gel-HMEM and 10mg of AMPS, mixing, regulating the pH of the solution to be alkaline, pumping nitrogen for 5 times, reacting for 2-3 hours by ultraviolet light, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PAMPS, wherein the chain length of the obtained spherical polyelectrolyte brush is 10nm.
Example 15
The difference from example 1 is that the addition amount of AMPS monomer is different and the procedure for photoinitiated emulsion polymerization is as follows: weighing 20mg of Gel-HMEM and 200mg of AMPS, mixing, regulating the pH of the solution to be alkaline, pumping nitrogen for 5 times, reacting for 2-3 hours by ultraviolet light, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PAMPS, wherein the chain length of the obtained spherical polyelectrolyte brush is 400nm.
Example 16
The difference from example 1 is that the addition amount of AMPS monomer is different and the procedure for photoinitiated emulsion polymerization is as follows: weighing 20mg of Gel-HMEM and 300mg of AMPS, mixing, regulating the pH of the solution to be alkaline, pumping nitrogen for 5 times, reacting for 2-3 hours by ultraviolet light, dialyzing and purifying the product by using a dialysis bag for three days, and freeze-drying the purified solution to obtain Gel-PAMPS, wherein the chain length of the obtained spherical polyelectrolyte brush is 380nm.
The foregoing embodiments are merely illustrative of the technical concept and features of the present invention, and are intended to enable those skilled in the art to understand the present invention and to implement the same, not to limit the scope of the present invention. All equivalent changes or modifications made according to the spirit of the present invention should be included in the scope of the present invention.
Claims (10)
1. A method for preparing a gelatin polyelectrolyte brush by a photoinitiated emulsion polymerization method is characterized in that after methacrylic acid gelatin nano particles with surface grafted with a photoinitiator are mixed with polyelectrolyte monomers, the pH value of a reaction system is regulated, and then ultraviolet lamp light initiation polymerization reaction is carried out in an anaerobic environment to prepare the gelatin spherical polyelectrolyte brush; wherein the polyelectrolyte monomer is selected from any one of an anionic polyelectrolyte monomer, a cationic polyelectrolyte monomer, a zwitterionic polyelectrolyte monomer or a neutral polyelectrolyte monomer;
when the polyelectrolyte monomer is an anionic polyelectrolyte monomer or a cationic polyelectrolyte monomer, regulating the pH of a reaction system until the methacrylic gelatin nano particles of the surface grafting photoinitiator and the polyelectrolyte monomer have opposite charges; when the polyelectrolyte monomer is a zwitterionic polyelectrolyte monomer or a neutral polyelectrolyte monomer, regulating the pH of a reaction system to the isoelectric point of the methacrylic acid gelatin nanoparticle of the surface grafting photoinitiator.
2. The method for preparing a gelatin polyelectrolyte brush according to claim 1, wherein the anionic polyelectrolyte monomers comprise acrylic acid, sodium p-styrenesulfonate, 2-acrylamido-2-methylpropanesulfonic acid; the cationic polyelectrolyte monomer comprises methacryloyloxyethyl trimethyl ammonium chloride, 2-aminoethyl ester hydrochloride and acryloyloxyethyl trimethyl ammonium chloride; the zwitterionic polyelectrolyte monomer comprises [2- (methacryloyloxy) ethyl ] dimethyl- (3-sulfopropyl) ammonium hydroxide, 3- [ [2- (methylendoyloxy) yl ] dimethylamino ] inner acid inner salt, 2-methacryloyloxyethyl phosphorylcholine; the neutral polyelectrolyte monomers include methacrylate, styrene, N-isopropyl acrylamide.
3. The method for preparing a gelatin polyelectrolyte brush according to claim 1, wherein the photoinitiator is 2- [ p- (2-hydroxy-2-methyl propiophenone) ] -glycol-acrylate (HMEM).
4. The method for preparing a gelatin polyelectrolyte brush according to claim 1, wherein the mass ratio of the polyelectrolyte monomer to the surface grafting photoinitiator of the methacrylic gelatin nanoparticle is (1-15): 1.
5. the method for preparing a gelatin polyelectrolyte brush by photoinitiated emulsion polymerization as claimed in claim 1, wherein the polymerization reaction time is 2-3 hours.
6. The method for preparing a gelatin polyelectrolyte brush by a photoinitiated emulsion polymerization process according to claim 1, wherein the prepared gelatin polyelectrolyte brush has a chain length of 10-400nm.
7. The method for preparing a gelatin polyelectrolyte brush by a photoinitiated emulsion polymerization process according to claim 1, comprising the steps of:
s1: gelatin is taken as a raw material, a desolvation method is adopted, and a cross-linking agent is added to enable the gelatin to self-assemble to form gelatin nano particles;
s2: surface modification is carried out on the prepared gelatin nano particles by using methacrylic anhydride to prepare methacrylic acid gelatin nano particles;
s3: grafting the photoinitiator HMEM on the surface of the methacrylic acid gelatin nanoparticle;
s4: mixing the methacrylic acid gelatin nano particles grafted with the photoinitiator on the surface with polyelectrolyte monomers, regulating the pH value of a reaction system, and then carrying out polymerization reaction under ultraviolet irradiation to obtain the gelatin spherical polyelectrolyte brush.
8. The method for preparing a gelatin polyelectrolyte brush by a photoinitiated emulsion polymerization process according to claim 7, wherein in step S2, the preparation of the methacrylic gelatin nanoparticle comprises the steps of:
(1) Mixing, stirring and dissolving the gelatin nano particles and carbonic acid-sodium bicarbonate buffer solution, and adjusting the pH value to be 8-10;
(2) Adding a certain amount of methacrylic anhydride, and carrying out light-proof reaction at 50-55 ℃;
(3) After the light-shielding reaction is finished, dialyzing and purifying the product in hot water, wherein the molecular weight cut-off of a dialysis bag is 8-14kDa;
(4) And freeze-drying the purified solution to obtain the required methacrylic gelatin nano-particles.
9. The method for preparing a gelatin polyelectrolyte brush by a photoinitiated emulsion polymerization method according to claim 7, wherein in the step S3, methacrylic acid anhydride modified methacrylic acid gelatin nanoparticles and the photoinitiator are mixed under nitrogen atmosphere and reacted for 2-3 hours at 70-90 ℃ to obtain the surface grafted photoinitiator methacrylic acid gelatin nanoparticles.
10. A gelatine spherical polyelectrolyte brush prepared according to the method for preparing a gelatine polyelectrolyte brush according to any one of claims 1-9.
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