CN117986444A

CN117986444A - Dynamic nano gel adhesive and preparation method and application thereof

Info

Publication number: CN117986444A
Application number: CN202311854078.5A
Authority: CN
Inventors: 陈云华; 李春晖
Original assignee: South China University of Technology SCUT
Current assignee: South China University of Technology SCUT
Priority date: 2023-12-29
Filing date: 2023-12-29
Publication date: 2024-05-07

Abstract

The invention belongs to the technical field of adhesives, and discloses a dynamic nanogel adhesive and a preparation method and application thereof. The method comprises the following steps: 1) Uniformly mixing AAPBA solution with mixed solution of N-isopropyl acrylamide, N, N' -methylene bisacrylamide and sodium dodecyl sulfate, regulating pH to be alkaline, heating and stirring, dialyzing, and regulating the concentration and pH value of the solution to obtain the nanogel adhesive; the KPS is added into the mixed solution or the solution after the two solutions are mixed. The method is simple, and the problem of low solid content of the precipitated polymer is solved; the prepared adhesive has temperature sensitivity, excellent adhesion effect at different temperatures, certain adhesion effect at different pH values, adhesion to tissues and good cell compatibility. The adhesives of the invention are useful for binding PVA gels and/or as tissue adhesives.

Description

Dynamic nano gel adhesive and preparation method and application thereof

Technical Field

The invention belongs to the technical field of adhesives, and particularly relates to a dynamic nanogel adhesive and a preparation method and application thereof.

Background

Hydrogels are a class of extremely hydrophilic three-dimensional network structure gels that swell rapidly in water and in this swollen state can hold a large volume of water without dissolution. Because of its high water content, it can act as an energy dissipating matrix, which can interact with the interface to prevent macroscopic movement. By physicochemical design of hydrogels, a series of adhesive patches or tough adhesives with injectable, adjustable cure time, degradable properties can be obtained.

However, most of the researches at present are macroscopic block hydrogel adhesives, the synthesis of the gel often needs external stimulation such as temperature rise, refrigeration cycle or ultraviolet crosslinking, in addition, two or more components are often needed to obtain the viscosity, the construction of the viscosity is often complex, and the formed block gel has uneven mechanical strength, which affects the adhesion effect and is inconvenient to apply in vivo minimally invasive surgery. It has been reported that inorganic nanoparticles are used as binders, for example, a gel that is not self-adhesive can be bonded directly with silica (SiO ₂) in a few seconds to achieve very strong adhesion (Rose, s.; prevoteau, a.; elziere, p.; hourdet, d.; MARCELLAN, a.; leibler, l.; nature 2014,505 (7483), 382-5.); ceria (CeCO ₂) was combined with SiO ₂ to form a nano-solution binder (Wu, h.; li, f.; wang, s.; lu, j.; li, j.; du, y.; sun, x.; chen, x.; gao, j.; ling, d.; biomaterials 2018,151,66-77.); the tantalum oxide (TaO _x) and SiO ₂ are compounded to form the core-shell nanoparticle solution which can be used as an adhesive and can be used for in vivo biological imaging (Shin,K.;Choi,J.W.;Ko,G.;Baik,S.;Kim,D.;Park,O.K.;Lee,K.;Cho,H.R.;Han,S.I.;Lee,S.H.;Lee,D.J.;Lee,N.;Kim,H.C.;Hyeon,T.,Nat Commun 2017,8,15807.)., although the application of the inorganic nanoparticle aqueous solution is convenient, the adhesive can only be applied at a higher concentration, has rigidity and can not be used for energy dissipation, if the adhesive is used in the field of tissue engineering, cytotoxicity exists, the degradation and metabolism speeds are slow, long-time in vivo retention can bring a certain hazard to body tissues, the mechanical strength of a nano layer formed by aggregation at a wound part is not adapted to that of soft tissues, and tissue inflammatory reaction is easy to be caused, so that the wound healing effect is influenced, and inflammatory reaction is caused. Therefore, the development of the polymer nanogel adhesive is helpful to break through the limitation of inorganic nanoparticles, because the polymer nanogel has the basic characteristics of hydrogel, such as high water content, properties like extracellular matrix and the like, and biocompatibility are more excellent than those of inorganic nanoparticles. Although the current method for synthesizing the nanogel is mature, the problems of complex operation, expensive equipment or low nanogel concentration and the like often exist, and the application of the nanogel is restricted; on the other hand, while nanogels have been used in biomedical applications, most of the applications are directed to drug release using nanogels as carriers for drugs, and few reports of use as tissue adhesives have been made.

In order to solve the problems that the adhesive is complex in preparation, the viscosity cannot be obtained in time, the application is inconvenient, and the like, the nano gel adhesive with simple preparation process, quick adhesion and convenient application can be developed, the viscosity of the nano gel adhesive under different conditions is explored, a general model of the nano gel adhesive is built, and the application range of the nano gel in biomedicine is widened for laying a foundation for using the nano gel as a tissue adhesive in the future.

Disclosure of Invention

In order to overcome the defects and shortcomings of the prior art, the primary purpose of the invention is to provide a preparation method of a dynamic nanogel adhesive. According to the invention, a temperature-sensitive monomer N-isopropyl acrylamide (NIPAM) and 3-acrylamide phenylboron (AAPBA) capable of forming dynamic chemical bonds are used as monomers, N' -Methylene Bisacrylamide (MBA) is used as a cross-linking agent, sodium Dodecyl Sulfate (SDS) is used as a surfactant, and a high molecular dynamic nanogel adhesive is obtained through aqueous phase precipitation polymerization initiated by potassium persulfate (KPS), so that the problem that the concentration of synthesized nanogel adhesive is always lower is broken through. Compared with hydrogel adhesives, inorganic nanoparticle adhesives and cyanoacrylate adhesives, the nanogel adhesive has the advantages of simple preparation, convenience in carrying, convenience in application, convenience in use, convenience in storage and the like, has temperature sensitivity and pH sensitivity, can regulate and control adhesion performance by regulating and controlling the temperature and pH value during application, and widens the application conditions of the adhesive and the application range of nanogel.

It is another object of the present invention to provide a dynamic nanogel adhesive obtained by the above preparation method.

It is a further object of the present invention to provide the use of the dynamic nanogel adhesive described above.

The aim of the invention is achieved by the following technical scheme:

a method for preparing a dynamic nanogel adhesive, comprising the following steps:

(1) Dissolving 3-acrylamidophenylboron (AAPBA) in an alkaline aqueous solution to obtain a AAPBA solution;

(2) Dissolving N-isopropyl acrylamide (NIPAM), N, N' -Methylene Bisacrylamide (MBA) and sodium dodecyl sulfate in an alkaline aqueous solution to obtain a mixed solution; adding an initiator KPS or not into the mixed solution;

(3) Mixing AAPBA the solution and the mixed solution in the step (2) uniformly, regulating the pH value to be alkaline, heating and stirring for 1-10 h, and dialyzing to obtain a nanogel solution; when the mixed solution in the step (2) is not added with the initiator KPS, the initiator KPS is added after AAPBA of the mixed solution in the step (2) is mixed;

(4) And (3) regulating the concentration and the pH value of the nanogel solution in the step (3) to obtain the nanogel adhesive.

The AAPBA in AAPBA solution in step (1) is at a concentration of 0.5g/100mL; the pH value of the alkaline aqueous solution is 10; AAPBA the solution is obtained by stirring and dissolving, the stirring time is 10-30 min, and the stirring speed is 100-300 rpm.

In the step (2), the concentration of NIPAM in the mixed solution is 5g/100mL, the concentration of MBA is 0.05g/100mL, and the concentration of Sodium Dodecyl Sulfate (SDS) is 0.05-0.6 g/100mL, preferably 0.3-0.6 g/100mL. The mass ratio of the initiator KPS to the initiator NIPAM is 0.05-0.2: 5.

The initiator is KPS.

The pH in step (3) was adjusted to 10.

The temperature of the heating in the step (3) is 65-75 ℃; the stirring time is preferably 7-9h, and the stirring speed is 100-200rpm.

The heating reaction is carried out under a protective atmosphere.

The molecular weight cut-off of the dialysis bag in the step (3) is 8-14 k.

The pH value in the step (4) is 7.4-10, and the concentration of the nanogel solution in the step (3) is regulated to be 0.05-8.5 g/100mL, preferably 2-8.5g/100mL.

The particle size of the nano gel is gradually reduced along with the temperature rise at 20-50 ℃; as the temperature decreases, its particle size increases. The nano gel of the invention is repeatedly treated at different temperatures, and the particle size can be reversible.

A dynamic nanogel adhesive is prepared by the preparation method.

The dynamic nanogel adhesives are used to adhere PVA gels and/or in tissue adhesives.

Compared with the prior art, the invention has the following technical advantages and beneficial effects:

(1) The invention adopts one-step precipitation polymerization to synthesize the dynamic polymer nano gel adhesive, and has simple operation and convenient synthesis.

(2) The invention overcomes the problem of low solid content of the precipitated polymer.

(3) The polymer nano gel adhesive prepared by the invention has a certain adhesion effect under different pH values, and can be applied under different pH values.

(4) The nano gel prepared by the invention has temperature sensitivity and excellent adhesion effect at different temperatures.

(5) The nanogel adhesive prepared by the invention can regulate the adhesiveness by the content of conditional SDS.

Drawings

FIG. 1 is a transmission electron microscope image and a particle size distribution diagram of the nanogel of example 1;

FIG. 2 is an SEM image and a particle size distribution chart of a nanogel according to example 1;

FIG. 3 is a graph showing the transmittance of nanogels as a function of temperature at different pH values in example 2;

FIG. 4 is a graph showing the variation of the particle size of the nanogel with temperature at different pH values in example 3;

FIG. 5 is a graph (a) and a graph (b) showing the particle size change of the nanogel at different pH values in example 4 after repeated temperature rise and drop;

FIG. 6 is a graph showing the adhesion properties of nanogels of different concentrations in examples 5-11;

FIG. 7 is a graph of the adhesion properties of the nanogels of different particle sizes of comparative examples 1,2, L, M and S representing three different sizes, large, medium and small, of the nanogel of example 10;

FIG. 8 is a graph showing the adhesion effect of the nanogel to the liver in example 10;

FIG. 9 is a graph showing the effect of cell activity of mouse fibroblasts co-cultured with nanogels for 5 days in example 12.

Detailed Description

The present invention will be further specifically described with reference to the following specific examples and drawings, but the embodiments of the present invention are not limited to the advantages and features of the present invention will become more apparent with the description, but the examples are merely exemplary in nature and do not limit the scope of the present invention in any way.

The following examples are illustrative of the sources of raw materials used: n-isopropyl acrylamide, triacrylamidophenylboronic acid, N' -methylenebisacrylamide, sodium dodecyl sulfate, and potassium persulfate were all purchased from Aladin.

Example 1

(1) 3-acrylamidophenylboronic acid was dissolved in aqueous sodium bicarbonate at ph=10 to give 10mL of a solution having a mass concentration of 0.5w/v% (i.e., 10mL of a solution containing 0.05g of 3-acrylamidophenylboronic acid).

(2) 10ML of a mixed solution of N-isopropylacrylamide, 0.05w/v% N, N' -methylenebisacrylamide, 0.5w/v% sodium dodecyl sulfate, and 0.1w/v% initiator KPS was prepared with an aqueous sodium bicarbonate solution having pH=10.

(3) Mixing the solutions in the step (1) and the step (2) together to obtain a mixed solution of (3-acrylamidophenylboronic acid and N-isopropyl acrylamide in a mass ratio of 0.5:5), stirring and fully mixing, and adjusting the pH=10 of the solution.

(4) And (3) carrying out water bath reaction on the mixed solution obtained in the step (3) at 70 ℃ for 8 hours, wherein the stirring speed is 150rpm.

(5) And (3) transferring the nanogel solution obtained in the step (4) into a dialysis bag for dialysis for 3d to obtain the nanogel solution with the concentration of 8.5 w/v%.

The nanogel solution is diluted to 0.05w/v% by ultrapure water, and is placed under a transmission electron microscope to observe the morphology of the nanogel, and a transmission electron microscope image and a particle size distribution chart are shown in figure 1.

The nanogel solution was diluted to 0.05w/v% with ultra pure water and the morphology of the nanogel was observed under a field emission high power Scanning Electron Microscope (SEM) and the particle size distribution diagram are shown in fig. 2.

Example 2

(1) 3-acrylamidophenylboronic acid was dissolved in aqueous sodium bicarbonate at ph=10 to give 10mL of a solution with a mass concentration of 0.5 w/v%.

(2) 10ML of a mixed solution of N-isopropylacrylamide, 0.05w/v% N, N' -methylenebisacrylamide, 0.5w/v% sodium dodecyl sulfate, and 0.1w/v% initiator KPS was prepared with an aqueous solution having pH=10.

The nanogel solution was diluted to 0.1w/v% with ultrapure water, and nanogel solutions having ph=7.4, ph=8.5, and ph=10 were respectively prepared, and the change in nanogel transmittance with temperature was characterized, and the result is shown in fig. 3.

Example 3

The nanogel solution was diluted to 0.1w/v% with ultrapure water, and nanogel solutions having ph=7.4, ph=8.5, and ph=10 were prepared, respectively, and the change in nanogel particle size with temperature was characterized, and the result is shown in fig. 4.

Example 4

First, the pH of the nanogel solution is adjusted: ph=7.4, ph=8.5 and ph=10, then the nanogel solution was diluted to 0.1w/v% with the same pH solution, and repeated temperature increase and decrease characterize the reversibility of the nanogel particle size with temperature, as shown in fig. 5. Fig. 5 is a graph (a) and a physical graph (b) of particle diameter change of the nanogel at different pH values in example 4 after repeated temperature increase and decrease.

Example 5

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive with ph=8.5 at 0.5 w/v%. The adhesive property graph of the nanogel of this example is shown in fig. 6.

Example 6

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive with ph=8.5 at 1 w/v%. The adhesive property graph of the nanogel of this example is shown in fig. 6.

Example 7

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive with ph=8.5 at 1.5 w/v%. The adhesive property graph of the nanogel of this example is shown in fig. 6.

Example 8

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive with ph=8.5 at 2 w/v%. The adhesive property graph of the nanogel of this example is shown in fig. 6.

Example 9

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive with ph=8.5 at 4 w/v%. The adhesive property graph of the nanogel of this example is shown in fig. 6.

Example 10

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive with a ph=8.5 at 6w/v%, and this adhesive was designated as S. The adhesive properties of the nanogel of this example are shown in figures 6 and 7 and the adhesion to the liver is shown in figure 8.

Example 11

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive with ph=8.5 at 8 w/v%. The adhesive property graph of the nanogel of this example is shown in fig. 6.

Example 12

(6) Diluting the nanogel solution obtained in the step (5) with a culture medium to obtain a culture medium containing nanogel, and co-culturing the culture medium with mouse fibroblasts.

Comparative example 1

1) 3-Acrylamidophenylboronic acid was dissolved in aqueous sodium bicarbonate at ph=10 to give 10mL of a solution with a mass concentration of 0.5 w/v%.

(2) A10 mL mixture of N-isopropylacrylamide, 0.05w/v% N, N' -methylenebisacrylamide, 0.2w/v% sodium dodecyl sulfate, and 0.1w/v% initiator KPS was prepared with an aqueous solution having a pH of 10.

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive of 6w/v%, ph=8.5, and this adhesive was designated as M. The adhesive properties of the nanogel of this comparative example are shown in figure 7.

Comparative example 2

(2) 10ML of a mixture of N-isopropylacrylamide, 0.05w/v% N, N' -methylenebisacrylamide, 0.05w/v% sodium dodecyl sulfate, and 0.1w/v% initiator KPS was prepared with an aqueous solution having pH=10.

(6) The nanogel solution obtained in step (5) was formulated into a nanogel adhesive with a ph=8.5 at 6w/v%, and this nanogel adhesive was designated as L. The adhesive properties of the nanogel of this comparative example are shown in figure 7.

Conclusion:

Fig. 1 is a transmission electron microscope Image and a particle size distribution diagram of the nanogel prepared in example 1, and it can be seen from fig. 1 that the nanogel has a relatively uniform size under the electron microscope, and the average particle size d=198±81nm is measured by Image J.

Fig. 2 is a scanning electron microscope Image and particle size distribution of the nanogel prepared in example 1, and it can be seen from fig. 2 that the nanogel is circular, and a small portion of the nanogel is aggregated, and the average particle size d=202±50nm is measured by Image J.

From fig. 3, it can be seen that the light transmittance of the nanogel decreases with increasing temperature, and the higher the pH, the higher the light transmittance.

From fig. 4, it can be seen that the particle size of the nanogel decreases with increasing temperature, and the particle size is larger at the same temperature as the pH value is larger.

As can be seen from fig. 5 (a), the particle size of the nanogel is reversible with repeated temperature increase and decrease, and the particle size is increased with temperature decrease; (b) The temperature-rising and temperature-lowering physical diagram is that the temperature-rising nanogel solution becomes milky to indicate that the particle size of the nanogel is reduced, and the temperature-lowering nanogel solution becomes clear and transparent to indicate that the hydrophilic particle size of the nanogel is enlarged.

FIG. 6 is a graph showing the adhesion properties of nanogels of different concentrations in examples 5-11. As can be seen from fig. 6, the nanogel concentration was the most viscous at 6%.

FIG. 7 is a graph of the adhesive properties of the nanogels of example 10, comparative example 1 and comparative example 2 (L, M and S represent three different sizes of nanogels, large, medium and small), showing that the size of the nanogels affects the adhesive strength, wherein the surfactant SDS content of example 10 is the largest, the size of the nanogels is the smallest, the adhesive properties are the strongest, the surfactant SDS content of comparative example 1 is the second, the adhesive properties are centered, the surfactant content of comparative example 2 is the smallest, the nanogel size is the largest, and the adhesive properties are the smallest.

FIG. 8 is a graph showing the adhesion effect of the nanogel to the liver in example 10. Figure 8 shows that the nanogel has good adhesion to the liver.

As can be seen from fig. 9, the mouse fibroblasts were free of obvious dead cells after five days of co-culture with the nanogel, indicating that the nanogel has good biocompatibility.

Claims

1. A preparation method of a dynamic nanogel adhesive is characterized by comprising the following steps of: the method comprises the following steps:

(1) Dissolving 3-acrylamidophenylboron in an alkaline aqueous solution to obtain AAPBA solution;

(2) Dissolving N-isopropyl acrylamide, N, N' -methylene bisacrylamide and sodium dodecyl sulfate in an alkaline aqueous solution to obtain a mixed solution; adding an initiator KPS or not into the mixed solution;

(4) Regulating the concentration and the pH value of the nanogel solution in the step (3) to obtain a nanogel adhesive;

The concentration of the 3-acrylamidophenylboron in the AAPBA g/100mL solution in the step (1); the pH of the alkaline aqueous solution is 10;

In the step (2), the concentration of N-isopropyl acrylamide in the mixed solution is 5g/100mL, the concentration of N, N' -methylene bisacrylamide is 0.05g/100mL, and the concentration of sodium dodecyl sulfate is 0.05-0.6 g/100mL; the mass ratio of the initiator KPS to the N-isopropyl acrylamide is 0.05-0.2: 5.

2. The method for preparing the dynamic nanogel adhesive according to claim 1, wherein:

the concentration of the sodium dodecyl sulfate is 0.3-0.6 g/100mL.

3. The method for preparing the dynamic nanogel adhesive according to claim 1, wherein: the pH in step (3) is adjusted to 10;

the temperature of the heating in the step (3) is 65-75 ℃; the stirring time is 7-9h, and the stirring speed is 100-200rpm.

4. The method for preparing the dynamic nanogel adhesive according to claim 1, wherein:

The pH value in the step (4) is 7.4-10, and the concentration of the nanogel solution in the step (3) is regulated to be 0.05-8.5 g/100mL;

The particle size of the nano gel is gradually reduced along with the temperature rise at 20-50 ℃; as the temperature decreases, its particle size increases.

5. The method of preparing a dynamic nanogel adhesive according to claim 4, wherein:

the concentration of the nanogel solution in the step (3) is regulated to be 2-8.5g/100mL.

6. The method for preparing the dynamic nanogel adhesive according to claim 1, wherein:

The AAPBA solution is obtained by stirring and dissolving, the stirring time is 10-60 min, and the stirring speed is 100-300 rpm;

the molecular weight cut-off of the dialysis bag in the step (3) is 8-14 k.

7. A dynamic nanogel adhesive obtained according to the preparation method of any one of claims 1 to 6.

8. The use of a dynamic nanogel adhesive according to claim 7, wherein: the dynamic nanogel adhesive is used to adhere PVA gels and/or as a tissue adhesive.