CN114920953A - PH-responsive antibacterial micelle and preparation method and application thereof - Google Patents
PH-responsive antibacterial micelle and preparation method and application thereof Download PDFInfo
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- CN114920953A CN114920953A CN202210744612.6A CN202210744612A CN114920953A CN 114920953 A CN114920953 A CN 114920953A CN 202210744612 A CN202210744612 A CN 202210744612A CN 114920953 A CN114920953 A CN 114920953A
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- 230000000844 anti-bacterial effect Effects 0.000 title claims abstract description 124
- 239000000693 micelle Substances 0.000 title claims abstract description 124
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 229920000058 polyacrylate Polymers 0.000 claims abstract description 77
- 239000002904 solvent Substances 0.000 claims abstract description 35
- 229920001577 copolymer Polymers 0.000 claims abstract description 29
- 239000000178 monomer Substances 0.000 claims abstract description 29
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract description 25
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 10
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- 238000000034 method Methods 0.000 claims description 35
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- -1 dimethylaminoethyl methacrylate bromo-n-butane quaternary ammonium salt Chemical class 0.000 claims description 21
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- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical group N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 7
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- 150000003242 quaternary ammonium salts Chemical class 0.000 description 3
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Images
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- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/07—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media from polymer solutions
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
- A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
- A01N25/04—Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/06—Unsaturated carboxylic acids or thio analogues thereof; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
- A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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- C08J2333/04—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters
- C08J2333/14—Characterised by the use of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical, or of salts, anhydrides, esters, amides, imides, or nitriles thereof; Derivatives of such polymers esters of esters containing halogen, nitrogen, sulfur, or oxygen atoms in addition to the carboxy oxygen
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
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- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention provides a pH responsive antibacterial micelle and a preparation method and application thereof, belonging to the technical field of high polymer antibacterial materials. The preparation method comprises the following steps: (1) carrying out polymerization reaction on an antibacterial acrylate monomer and a pH responsive acrylate monomer to obtain a polyacrylate antibacterial copolymer; (2) and (2) dissolving the polyacrylate antibacterial copolymer obtained in the step (1) in a good solvent to prepare a solution, then adding a poor solvent into the solution for self-assembly, and removing the solvent to obtain the antibacterial micelle. The preparation method disclosed by the invention is relatively mild in reaction conditions, simple to operate, high in sample yield and capable of realizing large-scale production. The prepared pH responsive antibacterial micelle has the capabilities of removing mature biomembranes and inhibiting formation of new biomembranes, can effectively prevent propagation of bacteria, and has good application prospects in the fields of medicines, biology, sanitation, foods and the like.
Description
Technical Field
The invention belongs to the technical field of high-molecular antibacterial materials, and particularly relates to a pH-responsive antibacterial micelle and a preparation method and application thereof.
Background
Bacteria easily cause bacterial infection, endanger human health and seriously affect public health safety. Studies have shown that 80% of bacterial infections are caused by biofilms, rather than planktonic bacteria. The bacterial biofilm is an accumulation area with dense survival of bacteria, the drug resistance of the bacteria inside is 1000 times that of planktonic bacteria, and more than 90 percent of the antibiotic resistance in clinic is directly caused. The Extracellular Polymer (EPS) accounts for 90% of the bacterial biofilm, and can prevent the antibacterial material from entering the biofilm, protect the internal bacteria from being killed, and reduce the sterilization efficiency. Efflux pumps expel the antimicrobial and reduce the concentration of the antimicrobial in the biofilm to allow the bacteria to develop resistance. Therefore, in the research of removing mature biofilms, the enhancement of the permeability and enrichment of antibacterial materials in the biofilms and the improvement of the sterilization efficiency in the biofilms have become international research hotspots. In order to meet the requirements of antibiotic membrane materials with high antibiotic activity, high permeability and high enrichment, the development of novel antibiotic materials to construct high-performance antibiotic membrane materials is urgently needed.
Disclosure of Invention
The invention aims to provide a pH-responsive antibacterial micelle, a preparation method and application thereof, and overcomes various problems in the prior art.
In order to achieve the above object or other objects, the present invention is achieved by the following aspects.
A preparation method of a pH-responsive antibacterial micelle is characterized by comprising the following steps:
(1) carrying out polymerization reaction on an antibacterial acrylate monomer and a pH responsive acrylate monomer to obtain a polyacrylate antibacterial copolymer;
(2) and (2) dissolving the polyacrylate antibacterial copolymer obtained in the step (1) in a good solvent to prepare a solution, then adding a poor solvent into the solution for self-assembly, and removing the solvent to obtain the antibacterial micelle.
Further, the polymerization reaction in the step (1) is selected from one of reversible addition-fragmentation chain transfer polymerization, free radical polymerization and atom transfer free radical polymerization. The reaction conditions for the polymerization reaction include, but are not limited to, those disclosed in the prior art.
Further, an initiator is added to the polymerization reaction in the step (1). The initiator includes, but is not limited to, various types of initiators commonly used. Preferably, the initiator is selected from azobisisobutyronitrile or dibenzoyl peroxide.
Preferably, the molar ratio of the antibacterial acrylate monomer to the initiator is (10-50): 1.
Further, a solvent is added during the polymerization reaction in the step (1). The solvent includes, but is not limited to, known organic solvents. Preferably, the solvent used for the polymerization reaction is one or two selected from THF, dichloromethane, acetonitrile, toluene.
Furthermore, the temperature of the polymerization reaction is 50-80 ℃, and the time of the polymerization reaction is 8-24 h.
Further, the antibacterial acrylate monomer is selected from one or more of dimethylaminoethyl methacrylate bromo-n-butane quaternary ammonium salt, dimethylaminoethyl methacrylate bromo-n-octane quaternary ammonium salt, dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt, dimethylaminoethyl methacrylate chloro-n-decane quaternary ammonium salt and dimethylaminoethyl methacrylate bromo-perfluoro-n-decane quaternary ammonium salt. The antibacterial acrylate monomer can be prepared by the prior art.
In the invention, when the side carbon chain of the quaternary ammonium salt is a straight chain and the length of the side carbon chain is not less than 8, the carbon chain can shield cations of the quaternary ammonium salt under other conditions, and when the micelle passes through the surface of the biological membrane, the electrostatic repulsion between the antibacterial micelle and the surface of the biological membrane can be reduced, so that the antibacterial micelle can permeate into the biological membrane, and the carbon chain with shorter length cannot play a role in shielding positive charges. The fluorocarbon chain has low surface energy and can rapidly penetrate through a biological membrane. Therefore, preferably, the antibacterial acrylate monomer is selected from one or two of dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt and dimethylaminoethyl methacrylate bromo-perfluoro-n-decane quaternary ammonium salt.
Further, the pH-responsive acrylate monomer is selected from one or two of vinyl methoxy silane, vinyl ethoxy silane, vinyl epoxy ethane and vinyl epoxy cyclohexane. The pH responsive acrylate monomer selected by the invention can be rapidly hydrolyzed in the acidic biomembrane to form active groups such as silicon hydroxyl and the like, and further reacts with hydroxyl and the like in the EPS matrix to form covalent bonds, so that the discharge of the acrylate monomer by an efflux pump in the biomembrane is avoided.
Further, in the step (1), the molar ratio of the antibacterial acrylate monomer to the pH-responsive acrylic monomer is (1-10): 1. when the molar ratio of the antibacterial acrylate monomer to the pH responsive acrylate monomer is greater than 10:1, the obtained copolymer has fewer active groups and cannot effectively react with EPS to form a covalent bond, so that the antibacterial micelle is easily discharged out of a biological membrane, the concentration of the antibacterial micelle in the biological membrane is reduced, and the capability of removing a mature biological membrane is weakened. When the molar ratio of the antibacterial acrylate monomer to the pH responsive acrylate monomer is less than 1:1, the content of the bactericidal group in the copolymer is low, the bactericidal efficiency of the antibacterial micelle in the biofilm is reduced, and the biofilm cannot be effectively removed. Preferably, the molar ratio of the antibacterial acrylate monomer to the pH-responsive acrylic monomer is (3-7): 1.
further, in the step (2), the self-assembly is performed at room temperature.
Further, in the step (2), the good solvent is selected from one or more of 1, 4-dioxane, N-dimethylformamide, THF and ethanol. The good solvent has good solubility for two chain segments in the polyacrylate antibacterial copolymer, and the polyacrylate antibacterial copolymer is dispersed in the good solvent in a molecular state.
Further, the poor solvent in the step (2) is ultrapure water.
Further, the solvent may be removed in step (2) of the present invention by using a technique commonly used in the art. Preferably, the solvent is removed in step (2) by dialysis or solvent evaporation. Preferably, the dialysis solution is ultrapure water.
Further, in the step (2), the mass concentration of the solution prepared by dissolving the polyacrylate antibacterial copolymer in the good solvent is 0.01-0.1%. When the mass solubility of the polyacrylate antibacterial copolymer is less than 0.01%, antibacterial micelles are difficult to form by adding poor solvents; when the mass solubility of the polyacrylate antibacterial copolymer is more than 0.1%, the copolymer is easy to precipitate in the water adding process, and uniform antibacterial micelles are not easy to form. Preferably, in the step (2), the mass concentration of the solution prepared by dissolving the polyacrylate antibacterial copolymer in the good solvent is 0.02-0.06%.
Furthermore, the volume ratio of the poor solvent to the good solvent in the step (2) is (0.05-0.5): 1. When the addition amount of the poor solvent is less than 0.05:1, the copolymer is easy to precipitate in the process of removing the solvent, and the antibacterial micelle is not easy to obtain; when the addition amount of the poor solvent is more than 0.5:1, the solution generates flocculent precipitates in the water adding process, and the antibacterial micelle cannot be obtained. The volume and rate of addition of the poor solvent determines the size of the final antimicrobial micelle. Further, in the step (2), the rate of adding the poor solvent is 10-50 mu L/min.
Preferably, the volume ratio of the poor solvent to the good solvent in the step (2) is (0.1-0.3): 1.
The invention also provides the polyacrylate antibacterial copolymer or antibacterial micelle prepared by the method.
The size of the antibacterial micelle prepared by the method is 150-1000 nm.
The invention also provides the application of the antibacterial micelle in the fields of medicine, biology, sanitation and food.
In the invention, an antibacterial acrylate monomer and a pH responsive acrylate monomer are polymerized to generate a polyacrylate antibacterial copolymer, and then the polyacrylate antibacterial copolymer is self-assembled to form the antibacterial micelle. In an anti-biofilm experiment, due to the acidic environment in the biofilm, the pH responsive acrylate structural unit is hydrolyzed to form silicon hydroxyl and the like under the environmental condition in the biofilm, and can react with EPS to form a covalent bond, so that the antibacterial micelle can keep a certain concentration in the biofilm, thereby quickly sterilizing, and being the pH responsive antibacterial micelle. The preparation method disclosed by the invention is relatively mild in reaction conditions, simple to operate, high in sample yield and capable of realizing large-scale production. The pH responsive antibacterial micelle prepared by the invention has the capability of removing mature biofilms and inhibiting new biofilm formation, can be prepared into a spray for the surface of a product needing sterilization, can remove the mature biofilms, can form an antibacterial coating on the solid surface, can prevent the new biofilm formation, can effectively prevent the propagation of bacteria, and has better application prospect in the fields of medicine, biology, sanitation, food and the like.
Drawings
FIG. 1 is an infrared image of the polyacrylate antibacterial copolymer prepared in example 1.
Fig. 2 is a graph showing the minimum inhibitory concentration of the polyacrylate antibacterial micelle prepared in example 1.
FIG. 3 is a scanning electron micrograph of a mature 48h Staphylococcus aureus biofilm before and after coculture with the polyacrylate antibacterial micelle prepared in example 1.
FIG. 4 is a confocal laser photograph of 48h mature Staphylococcus aureus biofilm before and after coculture with the polyacrylate antibacterial micelle prepared in example 1.
FIG. 5 is a graph showing the fluorescence intensity distribution of the polyacrylate antibacterial micelle prepared in example 1 after coculture with a 48h Staphylococcus aureus mature biofilm.
FIG. 6 is a scanning electron micrograph of the polyacrylate antibacterial micelle prepared in example 1 after co-culture with Staphylococcus aureus, which was sprayed on the surface of a silicon wafer.
FIG. 7 is a dynamic light scattering diagram of polyacrylate antibacterial micelles obtained in example 1, example 11, and example 12, respectively.
Detailed Description
The following description is provided for illustrative purposes and is not intended to limit the invention to the particular embodiments disclosed. The invention is capable of other and different embodiments and of being practiced or of being carried out in various ways, and its several details are capable of modification in various respects, all without departing from the spirit and scope of the present invention.
It should be noted that the features in the following embodiments and examples may be combined with each other without conflict. It is also to be understood that the terminology used in the examples is for the purpose of describing particular embodiments only, and is not intended to limit the scope of the present invention. Test methods in which specific conditions are not specified in the following examples are generally carried out under conventional conditions or under conditions recommended by the respective manufacturers.
When numerical ranges are given in the examples, it is understood that both endpoints of each of the numerical ranges and any value therebetween can be selected unless the invention otherwise indicated. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs and the description of the present invention, and any methods, apparatuses, and materials similar or equivalent to those described in the examples of the present invention may be used to practice the present invention.
In the embodiment of the present invention, the following methods are adopted for the minimum inhibitory concentration test of the antibacterial micelle, the mature biofilm elimination experiment, and the new biofilm formation inhibition experiment:
(1) and (3) testing the minimum inhibitory concentration: the antibacterial micelle was diluted with ultrapure water to give solutions having concentrations of 128. mu.g/mL, 64. mu.g/mL, 32. mu.g/mL, and 16. mu.g/mL, and 100. mu.L of the antibacterial micelle solution and 100. mu.L of 10. mu.L of the antibacterial micelle solution were added 6 And (3) co-culturing the CFU/mL staphylococcus aureus at 37 ℃, and measuring OD values at 0h, 4h, 8h, 12h, 16h, 20h and 24h to obtain the minimum inhibitory concentration.
(2) Mature biofilm removal experiments: 1 x 1cm coverslip in 48-well plate, 200. mu.L 10 concentration was dropped onto the surface 6 The Staphylococcus aureus in CFU/mL was cultured at 37 ℃ and replaced with fresh LB medium of pH 7.4 every 24 hours. After 48h, the membrane was washed twice with PBS solution at pH 7.4 to give a 48h mature biofilm. Then, the antibacterial micelle solution (200. mu.L, 32. mu.g/mL) was added dropwise, incubated at 37 ℃ for 2 hours, and washed twice with 1mL of PBS solution for confocal laser and scanning electron microscopy.
And (3) observing by a scanning electron microscope: fixing the bacteria of the sample obtained above with paraformaldehyde for 30min, then washing with PBS solution and water solution for 3 times respectively, drying the sample, spraying gold on the surface, and observing by using a scanning electron microscope.
Laser confocal observation: the sample obtained above was stained with PI and syto9 under dark conditions for 30min, washed twice with ultrapure water, observed by laser confocal observation, and analyzed with Image J software.
(3) Experiment for inhibiting formation of new biofilm: dripping the aqueous solution of the prepared polyacrylate antibacterial micelle on a 1 multiplied by 1cm silicon chip, drying, placing the silicon chip in a 24-pore plate, and adding 1mL of 10-concentration aqueous solution 8 Dripping the CFU/mL staphylococcus aureus on the surface of a sample, and culturing for 4 hours in a biological incubator at 37 ℃; then, the bacteria solution was removed, the sample was lightly washed with PBS solution 3 times, then the bacteria were fixed with paraformaldehyde for 30min, and then washed with PBS solution and aqueous solution 3 times, and after the sample was dried, the surface was sprayed with gold, and observed with a scanning electron microscope.
Example 1
(1) Preparation of polyacrylate antibacterial copolymer
Dissolving a monomer with the molar ratio of dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt to vinyl methoxysilane being 5:1 and azobisisobutyronitrile (wherein the molar ratio of dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt to azobisisobutyronitrile being 20:1) in THF (tetrahydrofuran), and fixing the obtained solutionThe content is 10 wt%, the solution is added into N 2 Heating to 65 ℃ under protection, preserving heat for 12h, precipitating the obtained reaction liquid by using normal hexane, and drying for later use.
(2) Preparation of polyacrylate antibacterial micelle
Dissolving the polyacrylate antibacterial copolymer in THF to prepare a solution with the concentration of 0.025%, slowly dripping ultrapure water into the solution, keeping the solution at room temperature overnight, placing the solution in a dialysis bag for dialysis, and removing THF to obtain the polyacrylate antibacterial micelle.
Infrared spectroscopy of the polyacrylate antibacterial copolymer prepared in example 1 gave the results shown in FIG. 1, from which 2919cm -1 Is the C-H characteristic absorption peak of the stretching vibration; 1723cm -1 Characteristic absorption peak for C ═ O; 1150cm -1 Is a characteristic absorption peak of Si-O-Si; 1317cm -1 Is a characteristic absorption peak of C-N. The copolymer is deduced to have the characteristic absorption peaks of quaternary ammonium salt and siloxane according to the results, which indicates that the polyacrylate antibacterial copolymer is successfully synthesized.
According to the method for testing the minimum inhibitory concentration, the polyacrylate antibacterial micelle prepared in this embodiment is tested, and the obtained minimum inhibitory concentration graph is shown in fig. 2, and it can be seen from the graph that the minimum inhibitory concentration of the antibacterial micelle prepared in this embodiment is 64 μ g/mL.
By adopting the method for the experiment of removing the mature biomembrane, the polyacrylate antibacterial micelle prepared in the embodiment is tested, the scanning electron microscope photos of the mature biomembrane of staphylococcus aureus obtained after 48h of culture and the polyacrylate antibacterial micelle prepared in the embodiment before and after 2h of co-culture are shown in figure 3, and the number of bacteria on the surface of the silicon wafer can be obviously reduced from figure 3, which shows that the antibacterial micelle can effectively remove the mature biomembrane. Further, laser confocal observation is carried out, the laser confocal results before and after co-culture of the 48h staphylococcus aureus mature biofilm and the polyacrylate antibacterial micelle prepared in the embodiment are shown in fig. 4, it can be seen from fig. 4 that all untreated biofilms are live bacteria (syto9 live bacteria are green), while biofilms co-cultured with the antibacterial micelle are mainly dead bacteria (PI dead bacteria are red), which also shows that the antibacterial micelle has good capability of removing the mature biofilm. The laser confocal observation result is further analyzed by Image J software, the obtained fluorescence intensity distribution diagram is shown in figure 5, and as can be seen from figure 5, the fluorescence intensity of red fluorescence in the biological membrane co-cultured with the antibacterial micelle is stronger, which indicates that more bacteria are dead in the biological membrane, and the antibacterial micelle can effectively kill the bacteria in the biological membrane.
The prepared polyacrylate antibacterial micelle is subjected to an experiment by adopting the method for inhibiting the formation of a new biofilm, a scanning electron microscope after the antibacterial micelle forms an antibacterial coating on the surface of a silicon wafer and is co-cultured with staphylococcus aureus for 4 hours is shown in figure 6, and a large number of cocci are adhered to the surface of the silicon wafer and are in an aggregation state; the antibacterial coating surface has bacteria adhesion but is in a dispersed state, and can inhibit the growth of a biological film.
Example 2
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), the molar ratio of dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt to vinyl methoxysilane is replaced by 7:1, the size of the obtained micelle is 358nm, the micelle has the effect of removing a mature biomembrane through the detection of a mature biomembrane removing experiment and a new biomembrane formation inhibiting experiment, and the polyacrylate micelle has the capability of inhibiting the growth of a new biomembrane after film formation, so that the polyacrylate micelle has the capability of resisting the biomembrane.
Example 3
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), the dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt is replaced by dimethylaminoethyl methacrylate bromo-n-dodecane quaternary ammonium salt, the size of the obtained micelle is 389nm, the micelle has the effect of removing a mature biomembrane through detection of a mature biomembrane removing experiment and a new biomembrane formation inhibiting experiment, and the polyacrylate micelle has the capability of inhibiting the growth of the new biomembrane after film formation, so that the polyacrylate micelle has the anti-biofilm capability.
Example 4
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), the dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt is replaced by dimethylaminoethyl methacrylate bromo-n-octane quaternary ammonium salt, the size of the obtained micelle is 296nm, the micelle has the effect of removing a mature biomembrane through detection of a mature biomembrane removing experiment and a new biomembrane formation inhibiting experiment, and the polyacrylate micelle has the capability of inhibiting the growth of the new biomembrane after film formation, so that the polyacrylate micelle has the anti-biofilm capability.
Example 5
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), vinyl methoxy silane is replaced by vinyl ethylene oxide, the size of the obtained micelle is 418nm, the micelle has the effect of removing a mature biomembrane through the detection of a mature biomembrane removing experiment and a new biomembrane formation inhibiting experiment, and the polyacrylate micelle has the capability of inhibiting the growth of the new biomembrane after film formation, so that the polyacrylate micelle has the capability of resisting the biomembrane.
Example 6
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), THF is replaced by acetonitrile, the size of the obtained micelle is 318nm, the micelle has the effect of removing a mature biomembrane through detection of a mature biomembrane removing experiment and a new biomembrane formation inhibiting experiment, and the polyacrylate micelle has the capability of inhibiting the growth of the new biomembrane after film formation, so that the polyacrylate micelle has the capability of resisting the biomembrane.
Example 7
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), THF is replaced by dichloromethane, the size of the obtained micelle is 337nm, the micelle has the effect of removing a mature biofilm through detection of a mature biofilm removing experiment and a new biofilm formation inhibiting experiment, and the micelle has the capability of inhibiting the growth of a new biofilm after film formation, so that the polyacrylate micelle has the capability of resisting the biofilm.
Example 8
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), the molar ratio of dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt to azodiisobutyronitrile is changed to 40:1, the size of the obtained micelle is 541nm, the micelle has the effect of removing a mature biomembrane through detection of a mature biomembrane removing experiment and a new biomembrane formation inhibiting experiment, and the polyacrylate micelle has the capability of inhibiting the growth of a new biomembrane after film formation, so that the polyacrylate micelle has the capability of resisting the biomembrane.
Example 9
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (2), THF is replaced by N, N-dimethylformamide, the size of the obtained micelle is 302nm, the micelle has the effect of removing a mature biomembrane through the detection of a mature biomembrane removing experiment and a new biomembrane formation inhibiting experiment, and the polyacrylate micelle has the capability of inhibiting the growth of the new biomembrane after film formation, so that the polyacrylate micelle has the anti-biofilm capability.
Example 10
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (2), the concentration of 0.025% is replaced by the concentration of 0.04%, the size of the obtained micelle is 316nm, the mature biofilm removing effect is achieved through detection of a mature biofilm removing experiment and a new biofilm formation inhibiting experiment, and the new biofilm growth inhibiting effect is achieved after film formation, so that the polyacrylate micelle has the anti-biofilm capacity.
Example 11
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (2), the volume ratio of the ultrapure water to the THF is replaced by 0.3 percent, the size of the obtained micelle is 947nm, the micelle has the effect of removing a mature biomembrane through the test of removing the mature biomembrane and the test of inhibiting the formation of a new biomembrane, and the polyacrylate micelle has the capability of inhibiting the growth of the new biomembrane after the film is formed, so that the polyacrylate micelle has the capability of resisting the biomembrane.
Example 12
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (2), the volume ratio of the ultrapure water to the THF is replaced by 0.3 percent, the size of the obtained micelle is 255nm, the micelle has the effect of removing a mature biomembrane through the test of removing the mature biomembrane and the test of inhibiting the formation of a new biomembrane, and has the capability of inhibiting the growth of the new biomembrane after the film is formed, so that the polyacrylate micelle has the capability of resisting the biomembrane.
As a result of measuring a dynamic light scattering pattern at room temperature using a powder particle size analyzer using 1mL of the aqueous polyacrylate antibacterial micelle solutions obtained in example 1, example 11 and example 12 at a concentration of 300. mu.g/mL, respectively, it can be seen from FIG. 7 that the sizes of the micelles obtained by dropping 10%, 30% and 50% ultrapure water are 947nm, 324nm and 255nm, respectively.
Comparative example 1
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), the molar ratio of the dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt to the vinyl methoxysilane is replaced by 1:1, the size of the obtained micelle is 420nm, and the polyacrylate micelle is poor in sterilization effect detected by a new biofilm formation inhibition experiment because the monomer with the sterilization effect accounts for a small amount in the polymer and cannot effectively remove the biofilm.
Comparative example 2
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (1), the molar ratio of the dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt to the vinyl methoxysilane is replaced by 20:1, the size of the obtained micelle is 275nm, and the removal of the mature biomembrane needs to be higher in concentration through detection of a new biomembrane formation inhibition experiment, probably because the antibacterial micelle cannot form a covalent bond with the EPS matrix and is easily discharged out of the biomembrane through an efflux pump, the sterilization efficiency is reduced, and the mature biomembrane cannot be effectively removed.
Comparative example 3
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (2), the solution with the concentration of 0.025% is replaced by the solution with the concentration of 0.2%, partial precipitation at the bottom of the bottle can be observed in the process of adding ultrapure water, the precipitation is obviously increased after dialysis, and the antibacterial micelle solution cannot be obtained.
Comparative example 4
Polyacrylate antibacterial micelle was prepared according to the method of example 1 except that: in the step (2), 0.3% of the volume ratio of ultrapure water to THF is replaced by 0.7%, and as the water addition amount increases, flocculent precipitates appear, so that an antibacterial micelle solution cannot be obtained.
The experimental results are combined to show that the polyacrylate antibacterial copolymer is synthesized by RAFT polymerization, and the polyacrylate antibacterial micelle is formed by self-assembly. The polyacrylate antibacterial micelle prepared by the method has the effect of removing mature biomembranes, and has the capability of inhibiting the growth of new biomembranes after film formation, which indicates that the polyacrylate antibacterial micelle has the capability of resisting the biomembranes.
The foregoing embodiments are merely illustrative of the principles of the present invention and its efficacy, and are not to be construed as limiting the invention. Those skilled in the art can modify or change the above-described embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.
Claims (10)
1. A preparation method of a pH-responsive antibacterial micelle is characterized by comprising the following steps:
(1) carrying out polymerization reaction on an antibacterial acrylate monomer and a pH responsive acrylate monomer to obtain a polyacrylate antibacterial copolymer;
(2) and (2) dissolving the polyacrylate antibacterial copolymer obtained in the step (1) in a good solvent to prepare a solution, then adding a poor solvent into the solution for self-assembly, and removing the solvent to obtain the antibacterial micelle.
2. The method according to claim 1, wherein the antibacterial acrylate monomer is selected from one or more of dimethylaminoethyl methacrylate bromo-n-butane quaternary ammonium salt, dimethylaminoethyl methacrylate bromo-n-octane quaternary ammonium salt, dimethylaminoethyl methacrylate bromo-n-decane quaternary ammonium salt, dimethylaminoethyl methacrylate chloro-n-decane quaternary ammonium salt, and dimethylaminoethyl methacrylate bromo-perfluoro-n-decane quaternary ammonium salt.
3. The method of claim 1, wherein the pH-responsive acrylate monomer is selected from one or two of vinylmethoxysilane, vinylethoxysilane, vinyloxirane, and vinylepoxycyclohexane.
4. The method according to claim 1, wherein in the step (1), the molar ratio of the antibacterial acrylate monomer to the pH-responsive acrylic monomer is (1 to 10): 1.
5. the method according to claim 1, wherein the good solvent in the step (2) is one or more selected from the group consisting of 1, 4-dioxane, N-dimethylformamide, THF and ethanol.
6. The method according to claim 1, wherein in the step (2), the polyacrylate antibacterial copolymer is dissolved in the good solvent to prepare a solution having a mass concentration of 0.01% to 0.1%.
7. The method according to claim 1, wherein in the step (2), the volume ratio of the poor solvent to the good solvent is (0.05-0.5): 1.
8. The method according to claim 1, wherein the poor solvent is added at a rate of 10 to 50 μ L/min in the step (2).
9. The polyacrylate antibacterial copolymer or antibacterial micelle prepared by the preparation method according to any one of claims 1 to 8.
10. The polyacrylate antibacterial copolymer or antibacterial micelle as claimed in claim 9, which is used in the fields of medicine, biology, hygiene and food.
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