A responsive reversibly adhesive microgel, preparation method and application thereof

Abstract

The invention discloses a responsive reversibly adhesive microgel, a preparation method and an application. The method comprises: weighing a responsive monomer, methoxyethyl acrylate, dopamine methacrylamide and an initiator, and dissolving them in an organic solvent A; wherein the molar concentrations of the responsive monomer, methoxyethyl acrylate and dopamine methacrylamide are 10%-20%, 60%-80% and 10%-20% respectively; adding an organic solvent B into a three-necked flask, the reaction speed is 90-180r / min, and then an inert gas is introduced; adding the organic solvent A containing the monomer into the solvent B for reaction, the reaction time is 6-12 hours, and the reaction temperature is 60-80°C; dialyzing the obtained reaction product, and freeze-drying the obtained solution to obtain a microgel sample. The method introduces different pH or temperature responsive monomers, and the obtained microgel has different adhesion responsiveness.

Description

Technical Field

[0001] The present invention relates to the technical field of microgels, and in particular to a responsive reversibly adhesive microgel, a preparation method and an application thereof. Background Art

[0002] Hydrogels are made of hydrophilic polymers and have the characteristics of high water content and insoluble in water. Microgels are submicron particle systems of hydrogels that can respond quickly to changes in size of external stimuli. The stimulus-responsive behavior of microgel systems makes them suitable candidates for various applications, especially in drug delivery systems, where microgels provide larger surface area, high loading efficiency and higher drug bioavailability. In drug delivery systems, microgels that release drugs need to adhere to designated sites. By responding to external stimuli, microgels change their own adhesion and enrich at the target location, which can better play the role of drug release and treatment. Temperature and pH are the two most important stimulus conditions in smart drug delivery systems, and are also two important physiological parameters of the human body and biological systems. Therefore, they are often used in drug controlled release. By responding to different stimuli, targeted drug release is achieved to achieve the purpose of smart drug delivery. It is difficult to achieve the adhesion of macroscopic hydrogels to different substrates, and it is even more challenging to give microgels adhesion properties to substrates at the microscopic level. In the prior art, there is a Chinese patent with publication number CN114933719A, entitled: Environmentally responsive adhesion of zirconium ion cross-linked thermosensitive hydrogel and its preparation method. This method can significantly improve the adhesion performance of the hydrogel, form strong adhesion with the substrate surface, and achieve a cyclic reversible process of strong adhesion and de-adhesion by changing environmental conditions. However, the reversible adhesion of the hydrogel is only applicable to air environments, while in liquid environments such as underwater, due to the presence of the hydration layer, it is extremely difficult to achieve the adhesion of macroscopic hydrogels to different substrates. Under the difficulty of overcoming the size effect and other preparation process problems, it is extremely challenging to give underwater microgels reversible adhesion properties to the substrate. Summary of the invention

[0003] In order to overcome the defects in the prior art, the present invention provides a responsive reversibly adhesive microgel, a preparation method and an application thereof. Reversibly adhesive microgel particles with different responses can be constructed. After the stimulus response, the microgel exhibits hydrophobic properties and strong adhesion, while in the normal state, the adhesion is weak.

[0004] The technical solution adopted by the present invention is: in the first aspect, the present invention proposes a method for preparing a responsive reversibly adhesive microgel, comprising the following steps:

[0005] Step S1, weighing a responsive monomer, methoxyethyl acrylate, dopamine methacrylamide and an initiator, and dissolving them in an organic solvent A; wherein the molar concentrations of the responsive monomer, methoxyethyl acrylate and dopamine methacrylamide are 10%-20%, 60%-80% and 10%-20% respectively;

[0006] Step S2, adding organic solvent B into a three-necked flask, the reaction speed is 90-180r / min, and then introducing inert gas;

[0007] Step S3, adding organic solvent A containing responsive monomers into organic solvent B for reaction, the reaction time is 6-12 hours, and the reaction temperature is 60-80° C.;

[0008] Step S4: dialyze the obtained reaction product, and freeze-dry the obtained solution to obtain a microgel sample.

[0009] As a further improvement of the present invention, the responsive monomer is a pH and temperature responsive monomer, including (meth)acrylic acid, dimethylaminoethyl methacrylate or N-isopropylacrylamide.

[0010] As a further improvement of the present invention, the initiator used is an oil-soluble thermal initiator, including azobisisobutyronitrile or dibenzoyl peroxide.

[0011] As a further improvement of the present invention, the organic solvent A used includes N,N-dimethylformamide.

[0012] As a further improvement of the present invention, the organic solvent B used is a non-polar organic solvent, such as cyclohexane or n-hexane.

[0013] As a further improvement of the present invention, the ratio of the organic solvent A to the organic solvent B used is 1:10-1:20.

[0014] As a further improvement of the present invention, the inert gas includes N2 or Ar.

[0015] As a further improvement of the present invention, in step S4, during the dialysis treatment, the molecular weight cut-off of the dialysis bag is 8000-14000.

[0016] In a second aspect, the present invention provides a microgel prepared by the above-mentioned method for preparing the microgel.

[0017] In a third aspect, the present invention also proposes an application of the microgel, which is applied to the field of controlled drug release.

[0018] The beneficial effects of the present invention are:

[0019] (1) In mussel secretory mucin, dopamine (DOPA) containing phenolic hydroxyl groups is the key to its fast and strong wet adhesion. Phenolic hydroxyl groups can interact with any substrate, including metal coordination with metal oxides, hydrophobic interaction with hydrophobic interfaces, and hydrophilic interaction with hydrophilic interfaces. The adhesion monomer dopamine methacrylamide containing a catechol structure introduced during the polymerization can give the microgel wet adhesion properties, and the adhesion of the microgels in different states is very different.

[0020] (2) By introducing different pH or temperature responsive monomers, the obtained microgels will have different adhesion responsiveness;

[0021] (3) After the polymer reaches the response point, the hydrophilic and hydrophobic properties change, and the hydrophobicity of the entire microgel is enhanced, which enhances the adhesion performance of the hydrogel;

[0022] (4) By replacing different monomers, the stimuli-responsive adhesion of microgels can be diversified, providing diverse options for practical applications;

[0023] (5) This preparation method is simple, can quickly realize the large-scale preparation of microgels, and is conducive to industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0025] Figure 1 The figure is a schematic diagram of a preparation method of a responsive reversibly adhesive microgel according to the present invention;

[0026] Figure 2 Scanning electron micrograph of the microgel of sample A in Example 1 of the present invention;

[0027] Figure 3 Schematic diagram of the adhesion of microgels of sample A in Example 1 of the present invention at different temperatures tested by atomic force microscopy; Figure 4 This is a graph showing the adhesion of sample B of Example 2 of the present invention to a gold substrate at different pH values ​​using a quartz crystal microbalance;

[0028] Figure 5 This is a particle size distribution diagram of sample B in Example 2 of the present invention in different pH buffer solutions. DETAILED DESCRIPTION

[0029] Please refer to Figure 1 The method for preparing the microgel provided by the present invention comprises the following steps:

[0030] Step S1, weigh the responsive monomer, methoxyethyl acrylate, dopamine methacrylamide and initiator, and dissolve them in organic solvent A; wherein the molar concentrations of the responsive monomer, methoxyethyl acrylate and dopamine methacrylamide are 10%-20%, 60%-80% and 10%-20% respectively; the initiator is an oil-soluble thermal initiator, including azobisisobutyronitrile and dibenzoyl peroxide. The responsive monomer is a pH and temperature responsive monomer, including (meth) acrylic acid, dimethylaminoethyl methacrylate or N-isopropylacrylamide. Organic solvent A is an organic solvent with high polarity, including N,N-dimethylformamide.

[0031] Step S2, adding organic solvent B into a three-necked flask, the reaction speed is 90-180r / min, and then introducing inert gas, the inert gas is N2, Ar.

[0032] Step S3, adding organic solvent A containing monomers into solvent B for reaction, the reaction time is 6-12 hours, the reaction temperature is 60-80°C; the organic solvent B used is a non-polar organic solvent, including cyclohexane and n-hexane. The ratio of organic solvent A to organic solvent B used is 1:10-1:20.

[0033] Step S4, dialyzing the obtained reaction product, and freeze-drying the obtained solution to obtain a microgel sample. Specifically, the molecular weight cutoff of the dialysis bag is 8000-14000.

[0034]

Implementation Case 1

[0035] Weigh 0.16g N-isopropylacrylamide, 1g methoxyethyl acrylate, 0.5g dopamine methacrylamide, 0.0108g azobisisobutyronitrile and dissolve in 5ml N,N-dimethylformamide, add 100ml n-hexane into a three-necked flask, rotate at 120r / min, introduce inert gas Ar, and then add DMF solution containing monomers. Set the temperature to 60°C. React for 12 hours. Take out the lower precipitated reactant and dialyze with deionized water. The molecular weight of the dialysis bag is 8000-14000. Dialyze for 5 days, and replace the deionized water every 12 hours. The obtained solution is freeze-dried to obtain sample A, such as Figure 2 shown. Figure 3 The adhesion of the microgels of sample A at different temperatures tested by atomic force microscopy, T>T LCST The microgel has strong adhesion, T <T LCST The adhesion of microgels is weak.

[0036]

Implementation Case 2

[0037] Weigh 0.1 g of acrylic acid, 1.25 g of methoxyethyl acrylate, 0.425 g of dopamine methacrylamide, and 0.0108 g of azobisisobutyronitrile and dissolve them in 5 ml of N,N-dimethylformamide. Add 80 ml of cyclohexane to a three-necked flask, set the rotation speed to 120 r / min, introduce an inert gas N2 or Ar, and then add the DMF solution containing the monomers. Set the temperature to 60 °C. React for 12 hours. After taking out the lower-layer precipitated reactant, dialyze it with deionized water. The molecular weight of the dialysis bag is 8000 - 14000, and dialyze for 5 days, changing the deionized water every 12 hours. The obtained solution is freeze-dried to obtain the prepared sample B. Figure 4 To use a quartz crystal microbalance to test the adhesion of sample B of this example to the gold substrate at different pH values, the microgel has strong adhesion in the pH < pKa buffer solution and accumulates and adheres on the surface of the balance substrate. Replace with neutral deionized water and the pH > pKa buffer solution for rinsing, and the mass of the metal substrate decreases. The adhesion of the microgel decreases at high pH and detaches from the substrate surface. Figure 5 This is the particle size distribution diagram of sample B of this example in different pH buffer solutions.

[0038] The embodiments of the present invention have been described in detail above in conjunction with the accompanying drawings. However, the present invention is not limited to this. All changes that can be made within the knowledge of those skilled in the art without departing from the purpose of the present invention are within the protection scope of the claims of the present invention.

Claims

1. A method for preparing a responsive reversibly adhesive microgel, characterized in that: The following steps are involved: Step S1, weighing a responsive monomer, methoxyethyl acrylate, dopamine methacrylamide and an initiator, and dissolving them in an organic solvent A, wherein the organic solvent A used includes N,N-dimethylformamide; the responsive monomer is a pH and temperature responsive monomer, including (meth)acrylic acid, dimethylaminoethyl methacrylate or N-isopropylacrylamide; wherein the molar concentrations of the responsive monomer, methoxyethyl acrylate and dopamine methacrylamide are 10%-20%, 60%-80% and 10%-20% respectively; Step S2, adding an organic solvent B into a three-necked flask, wherein the organic solvent B used is a non-polar organic solvent such as cyclohexane or n-hexane, and the reaction speed is 90-180 r / min, and then an inert gas is introduced; Step S3, adding organic solvent A containing responsive monomers to organic solvent B for reaction, wherein the ratio of organic solvent A to organic solvent B is 1:10-1:20, the reaction time is 6-12 hours, and the reaction temperature is 60-80° C.; Step S4: dialyze the obtained reaction product, and freeze-dry the obtained solution to obtain a microgel sample, which is applied in the field of controlled drug release.

2. The method for preparing microgel according to claim 1, characterized in that: The initiator used is an oil-soluble thermal initiator, including azobisisobutyronitrile or dibenzoyl peroxide.

3. The method for preparing microgel according to claim 1, characterized in that: The inert gas includes N2 or Ar.

4. The method for preparing microgel according to claim 1, characterized in that: In step S4, during the dialysis treatment, the molecular weight cut-off of the dialysis bag is 8000-14000.

5. A microgel, characterized in that: The microgel is prepared by the preparation method of any one of claims 1 to 4.

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