Gel microsphere and preparation method thereof based on bubble generation and polymer in-situ deposition

Abstract

The invention discloses gel microspheres and a preparation method thereof based on bubble generation and polymer in-situ deposition, and belongs to the technical field of high polymer materials. The preparation method comprises the following steps: mixing polyacrylamide (PAM) or partially hydrolyzed polyacrylamide (HPAM) gel with the concentration of 1-20.0% (w / v) with a Fenton-like system with the concentration of 1-10%, which is prepared from hydrogen peroxide and complex iron in a molar ratio of (10.2-10.5): 1, according to a mass ratio of 1: (5-12), putting the mixture into a container for reaction, and adding a free radical quencher after the reaction is finished, so as to obtain the gel microspheres. According to the method, polymer degradation and bubble in-situ generation are synchronously achieved through a Fenton-like reaction, polymer fragments generated through degradation and system salt are self-assembled on a gas-liquid interface to form a compact shell layer, and the structured microspheres with the hollow interior are constructed in one step. The prepared gel microspheres have the diameter of 10-50 microns, the shell thickness of 1-5 microns and the compressive strength of 2-5 MPa, and have the advantages of simple process, high controllability, compact shell and high strength.

Description

Technical Field

[0001] This invention belongs to the field of polymer materials technology, specifically relating to gel microspheres. This invention also relates to a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition. Background Technology

[0002] Gel microspheres with core-shell structures or internal cavities have broad application prospects in drug controlled release, cell culture, catalyst carriers, cosmetics, and the food industry. The thickness, density, and mechanical strength of the shell are key factors determining the performance of these microspheres.

[0003] Currently, common techniques for preparing such microspheres mainly include layer-by-layer self-assembly, microfluidics, emulsion templates, and phase separation. For related techniques of layer-by-layer self-assembly, refer to the research progress on the preparation of hydrogel antibacterial microspheres and their application in bioengineering published in the *Journal of Composite Materials* by Meng Fengyu, Jiang Yitong, Yin Zhenyang, et al., which discloses a method of constructing the target structure by alternately adsorbing substances with different charges (such as chitosan-ammonium polyphosphate) and depositing them layer by layer on the matrix surface. For specific applications of microfluidics, see Tang Shilin's research results, "Preparation and Performance Study of Multifunctional Hydrogel Microspheres and Membranes," which uses microfluidic chips to precisely control fluid flow rate and interfacial tension, first forming uniformly sized droplets, and then preparing gel microspheres through subsequent polymerization and other treatments. For the technical concept of the emulsion template method, refer to the research by Yang S, Li Z, Qu G, et al., "Composite hydrogel microspheres modulate intestinal inflammation via releasing HA modified liposomes@4-OI targeting." "M1macrophages" uses emulsion droplets as templates to coat or crosslink polymers at the droplet interface. Subsequently, cavity and shell structures are formed by removing the template or utilizing differences in internal components. The related technology of phase separation method is mentioned in the research of Wang Yue, Ao Qing, Li Yingli et al., "Research Progress on the Preparation of Hydrogel Antibacterial Microspheres and Their Application in the Field of Bioengineering". This method utilizes the phase separation of polymer systems under specific conditions such as temperature and solvent changes to form microsphere prototypes with cavity or core-shell structures, which are then solidified to obtain the finished product.

[0004] However, the aforementioned existing preparation technologies generally have significant limitations: First, the shell thickness and strength are difficult to control in a coordinated manner. For high molecular weight polymers such as partially hydrolyzed polyacrylamide (HPAM), due to their long molecular chains and large steric hindrance, it is difficult to form a dense, uniform, and sufficiently mechanically strong thin shell at the micron-scale emulsion droplet interface through simple adsorption or crosslinking. Extremely low raw material concentrations or complex interface activation treatments are often required, resulting in a narrow process window and poor repeatability. Second, to obtain a shell with sufficient strength, multiple layer-by-layer depositions using small molecule emulsifiers or oligomers are usually required. This process is cumbersome and time-consuming, and defects may exist between the multi-layer interfaces, seriously affecting the integrity and stability of the shell. More importantly, it is difficult to achieve the construction of a single-layer, in-situ reinforced shell. Third, the controllability of internal cavity formation is poor. Existing technologies mostly form cavities by removing templates or utilizing differences in internal crosslinking density. This is not only complex but also suffers from low controllability of cavity size and distribution. Summary of the Invention

[0005] The first objective of this invention is to provide a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition, which can generate gel microspheres with a single-layer shell in a single step under mild conditions.

[0006] Another object of the present invention is to provide gel microspheres.

[0007] The first technical solution adopted in this invention is a gel microsphere preparation method based on bubble generation and in-situ polymer deposition, which involves mixing a polyacrylamide gel with a concentration of 1.0-20.0% (w / v) with a Fenton-like system with a concentration of 1-10% and then reacting the mixture.

[0008] The first technical solution of the present invention is further characterized by: Polyacrylamide gels are formulated using polyacrylamide or partially hydrolyzed polyacrylamide.

[0009] The degree of hydrolysis of partially hydrolyzed polyacrylamide is 10-30%.

[0010] Polyacrylamide or partially hydrolyzed polyacrylamide has a molecular weight of 5-60 million.

[0011] The Fenton-like system is an aqueous solution prepared by hydrogen peroxide and complexed iron in a molar ratio of (10.2~10.5):1.

[0012] The hydrogen peroxide is selected from at least one of sodium percarbonate, percarbonamide, sodium perborate, calcium peroxide, and magnesium peroxide.

[0013] Complexed iron is formed by complexing iron ions with ethylenediaminetetraacetic acid salt, citrate, oxalate, tartrate or gluconate, wherein the iron ions are divalent or trivalent.

[0014] The mass ratio of polyacrylamide gel to Fenton-like system is 1:(5-12).

[0015] The reaction temperature is 60-80℃, and the reaction time is 4-24h.

[0016] Another technical solution adopted in this invention is gel microspheres, which are prepared according to the above-mentioned gel microsphere preparation method based on bubble generation and in-situ polymer deposition. The microspheres are hollow inside and the shell is composed of polyacrylamide degradation products. The viscosity of the degradation products has an average molecular weight of 5 to 2 million. The microspheres have a diameter of 10-50 μm, a shell thickness of 1-5 μm, and a shell compressive strength of 2-5 MPa.

[0017] The beneficial effects of this invention are: 1. The preparation method of this invention simultaneously constructs cavities and shells in a one-step process: utilizing the chemical reaction of the Fenton-like system and controlling the reaction conditions, the degradation of polyacrylamide polymers and the in-situ generation of gas occur simultaneously. The generated gas acts as a dynamic template to form stable cavities with controllable dimensions within the gel matrix. Simultaneously, polymer fragments of specific molecular weights generated during degradation and salt components in the system undergo synergistic self-assembly at the gas-liquid interface, spontaneously forming a dense, single-layer reinforced shell. Thus, structured gel microspheres with a core-shell structure are efficiently and controllably prepared in a single reaction step.

[0018] 2. The method of the present invention utilizes polyacrylamide polymers to degrade and generate medium molecular weight fragments instead of the original macromolecules as shell materials. The medium molecular weight fragments have better interfacial migration and alignment capabilities. At the same time, the addition of salt further strengthens the shell structure through electrostatic shielding and bridging effects, thereby achieving high strength of the single-layer shell and overcoming the problem that macromolecules are difficult to form a dense thin shell.

[0019] 3. The preparation method of the present invention controls the gas generation rate and bubble size by changing the oxidant concentration, and controls the matrix viscosity and bubble stability by controlling the gel concentration, thereby achieving adjustable size of the internal cavity and shell thickness of the microspheres. Attached Figure Description

[0020] Figure 1 These are typical morphology images of the gel microspheres prepared in Example 1 of this invention under a 100 μm scanning electron microscope (SEM); Figure 2 These are typical morphology images of the gel microspheres prepared in Example 2 of this invention under a 50 μm scanning electron microscope (SEM); Detailed Implementation The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments.

[0021] This invention discloses a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition, specifically as follows: A polyacrylamide gel and a Fenton-like system were mixed at a mass ratio of 1:(5-12), and the mixture was placed in a container to initiate a redox reaction. Specifically, the concentration of polyacrylamide gel is 1.0-20.0% (w / v), which is a hydrogel prepared with polyacrylamide (PAM) with a molecular weight of 5 million-60 million or partially hydrolyzed polyacrylamide (HPAM), and the degree of hydrolysis of partially hydrolyzed polyacrylamide (HPAM) is 10-30%.

[0022] The Fenton-like system, acting as a depolymerizing agent, is formulated from hydrogen peroxide and complexed iron. The hydrogen peroxide, acting as the oxidizing agent, is at least one of sodium percarbonate (SPC), percarbonamide, sodium perborate, calcium peroxide, and magnesium peroxide; the complexed iron, acting as the reducing agent, is Fe. 2+ or Fe 3+ Stable complexes are formed with ethylenediaminetetraacetic acid salt, citrate, oxalate, tartrate, and gluconate complexing agents. In preparation, water is used as the solvent, and hydrogen peroxide and complexed iron are added at a molar ratio of (10.2~10.5):1, ultimately forming an aqueous solution with an effective content of 1-10% hydrogen peroxide and complexed iron.

[0023] The reaction environment pressure is atmospheric pressure or a slight negative pressure of 95-101.325 kPa. A slight negative pressure facilitates bubble formation, while excessively high or low pressures are detrimental. The reaction temperature is 60-80℃. After the reaction is triggered, hydrogen peroxide decomposes under the catalysis of complexed iron, producing oxygen and hydroxyl radicals. Oxygen forms numerous micron-sized bubbles within the gel network; hydroxyl radicals attack the polyacrylamide molecular chains, causing chain-breaking degradation. By controlling the oxidant concentration, reaction temperature, and time, the degree of degradation can be controlled, resulting in degradation products containing a large number of polymer fragments with medium molecular weights (5-2 million average viscosity). These polymer fragments, containing hydrophilic amide groups and some hydrophobic carbon-carbon segments, are amphiphilic and tend to migrate and accumulate at the gas-liquid interface, i.e., the bubble surface. Hydrogen peroxide decomposes in the system to form salts. These salts compress the electric double layer of the polymer fragments, reducing their hydration level and promoting further compact packing and physical entanglement at the interface. Simultaneously, the salts also act as a "bridging" agent, enhancing the interaction between polymer fragments. This process creates a dense, reinforced shell around the bubble, composed of polymer fragments from degradation and salt.

[0024] The reaction time is 4-24 hours. After the reaction is completed, the reaction is terminated by adding the free radical quencher sodium thiosulfate or tert-butanol. The gel microspheres are then obtained by centrifugation, filtration or static separation.

[0025] The gel microspheres prepared by this method have an internal cavity as a core and a shell enclosing the core. The shell is mainly composed of degradation products of polyacrylamide. The microsphere diameter is 10-50 μm, the shell thickness is 1-5 μm, and the shell compressive strength ranges from 2-5 MPa. The microsphere size and shell thickness can be controlled by adjusting the initial concentration of the polymer, the concentration of the oxidant, and the reaction time in the reaction system.

[0026] Example 1 This embodiment discloses a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition, specifically as follows: Prepare a 1% (w / v) PAM aqueous solution with an initial molecular weight of approximately 5 million; use sodium percarbonate and EDTA-Fe in a molar ratio of 10.2:1. 3+ Prepare a 1% Fenton-like system; rapidly mix the PAM aqueous solution and the Fenton-like system at a mass ratio of 1:5 until homogeneous. Transfer the mixture to several well-sealed glass vials with sufficient headspace and incubate in an 80°C water bath for 4 hours. After the reaction is complete, add sodium thiosulfate, a free radical quencher, to terminate the reaction.

[0027] Remove the vial and cool it in an ice bath. Dilute the product with deionized water, centrifuge to collect the solid matter, and wash it twice with deionized water.

[0028] The obtained product was subjected to critical point drying and then sputter-coated with gold. Its morphology was observed using a scanning electron microscope (SEM). Figure 1 As shown, numerous spherical structures with diameters ranging from 15 to 40 μm can be observed, each containing a distinct cavity. The cavity walls (shells) are single-layered, exhibiting a continuous and relatively dense morphology, with a shell thickness of 1–5 μm. The compressive strength of these microspheres was measured to be 2 MPa using a micromanipulator and a microforce sensor.

[0029] Example 2 This embodiment discloses a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition. Specifically, it involves preparing a 1% (w / v) HPAM aqueous solution with a degree of hydrolysis of 10% and an initial HPAM molecular weight of approximately 10 million; and using sodium percarbonate and EDTA-Fe in a molar ratio of 10.5:1. 3+ Prepare a 1% Fenton-like system; rapidly mix the HPAM aqueous solution and the Fenton-like system at a mass ratio of 1:5 until homogeneous. Transfer the mixture to several well-sealed glass vials with sufficient headspace and incubate at 70°C for 8 hours. After the reaction is complete, add sodium thiosulfate as a free radical quencher to terminate the reaction.

[0030] Remove the vial and cool it in an ice bath. Dilute the product with deionized water, centrifuge to collect the solid matter, and wash it twice with deionized water.

[0031] The obtained product was subjected to critical point drying and then sputter-coated with gold. Its morphology was observed using a scanning electron microscope (SEM). Figure 2 As shown, numerous spherical structures with diameters ranging from 20 to 40 μm can be observed, each containing a distinct cavity. The cavity walls (shells) are single-layered, exhibiting a continuous and relatively dense morphology, with a shell thickness of 1–2 μm. The compressive strength of these microspheres was measured to be 5 MPa using a micromanipulator and a microforce sensor.

[0032] Example 3 This embodiment discloses a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition, specifically: preparing a 10% (w / v) PAM aqueous solution, the initial molecular weight of PAM being approximately 10 million; using percarbonamide and sodium citrate–Fe in a molar ratio of 10.2:1. 2+ A 5% Fenton-like system was prepared by rapidly mixing the PAM aqueous solution and the Fenton-like system at a mass ratio of 1:5. The mixture was then transferred to several well-sealed glass vials with sufficient headspace and placed in a 70°C water bath for 14 hours. After the reaction was completed, sodium thiosulfate, a free radical quencher, was added to terminate the reaction.

[0033] Remove the vial and cool it in an ice bath. Dilute the product with deionized water, centrifuge to collect the solid matter, and wash it twice with deionized water.

[0034] Example 4 This embodiment discloses a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition. Specifically, it involves preparing a 10% (w / v) HPAM aqueous solution with a degree of hydrolysis of 30% and an initial molecular weight of approximately 25 million for HPAM; and using sodium perborate and sodium citrate–Fe in a molar ratio of 10.5:1. 2+ Prepare a 10% Fenton-like system; rapidly mix the HPAM aqueous solution and the Fenton-like system at a mass ratio of 1:7 until homogeneous. Transfer the mixture to several well-sealed glass vials with sufficient headspace and incubate in a 60°C water bath for 18 hours. After the reaction is complete, add sodium thiosulfate, a free radical quencher, to terminate the reaction.

[0035] Remove the vial and cool it in an ice bath. Dilute the product with deionized water, centrifuge to collect the solid matter, and wash it twice with deionized water.

[0036] Example 5 This embodiment discloses a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition. Specifically, a 20% (w / v) PAM aqueous solution is prepared, with an initial molecular weight of approximately 60 million PAM. A 5% Fenton-like system is prepared using calcium peroxide and ferrous gluconate at a molar ratio of 10.2:1. The PAM aqueous solution and the Fenton-like system are rapidly mixed at a mass ratio of 1:12. The mixed solution is transferred to multiple well-sealed glass vials with sufficient headspace and placed in a 60°C water bath for a constant temperature reaction for 24 hours. After the reaction is completed, sodium thiosulfate, a free radical quencher, is added to terminate the reaction.

[0037] Remove the vial and cool it in an ice bath. Dilute the product with deionized water, centrifuge to collect the solid matter, and wash it twice with deionized water.

[0038] Example 6 This embodiment discloses a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition. Specifically, a 20% (w / v) HPAM aqueous solution is prepared with a degree of hydrolysis of 20%, and the initial molecular weight of HPAM is approximately 5 million. Magnesium peroxide and Fe are used in a molar ratio of 10.3:1. 3+ - Prepare a 3% Fenton-like system using sodium tartrate; rapidly mix the HPAM aqueous solution and the Fenton-like system at a mass ratio of 1:8 until homogeneous. Transfer the mixture to several well-sealed glass vials with sufficient headspace and place them in an 80°C water bath for 10 hours. After the reaction is complete, add sodium thiosulfate as a free radical quencher to terminate the reaction.

[0039] Remove the vial and cool it in an ice bath. Dilute the product with deionized water, centrifuge to collect the solid matter, and wash it twice with deionized water.

[0040] Example 7 This embodiment discloses a method for preparing gel microspheres based on bubble generation and in-situ polymer deposition. Specifically, it involves preparing a 5% (w / v) HPAM aqueous solution with a degree of hydrolysis of 15% and an initial molecular weight of approximately 7 million for HPAM; and using magnesium peroxide and Fe in a molar ratio of 10.3:1. 3+ - Prepare a 3% Fenton-like system using sodium oxalate; rapidly mix the HPAM aqueous solution and the Fenton-like system at a mass ratio of 1:10 until homogeneous. Transfer the mixture to several well-sealed glass vials with sufficient headspace and incubate in an 80°C water bath for 10 hours. After the reaction is complete, add sodium thiosulfate as a free radical quencher to terminate the reaction.

[0041] Remove the vial and cool it in an ice bath. Dilute the product with deionized water, centrifuge to collect the solid matter, and wash it twice with deionized water.

[0042] The preparation method of this invention precisely controls parameters such as the ratio of polyacrylamide gel to Fenton-like system, reaction temperature, and time. Utilizing a Fenton-like reaction, it simultaneously achieves polymer degradation and in-situ bubble generation, allowing the medium-molecular-weight polymer fragments generated during degradation to synergistically self-assemble with the system's salts at the gas-liquid interface, constructing hollow, dense, and high-strength gel microspheres in one step. This method eliminates the need for complex template removal or multi-layer deposition steps, offering a simple and highly controllable process. By adjusting the initial polymer concentration, oxidant concentration, and reaction conditions, the microsphere diameter, shell thickness, and compressive strength can be flexibly controlled, effectively overcoming the limitations of traditional preparation techniques such as difficulty in shell control, poor cavity controllability, and cumbersome steps. The prepared gel microspheres have broad application prospects in multiple fields such as drug controlled release, cell culture, and catalyst carriers.

Claims

1. A method for preparing gel microspheres based on bubble generation and in-situ polymer deposition, characterized in that, A 1.0-20.0% (w / v) polyacrylamide gel was mixed with a 1-10% Fenton-like system and then reacted.

2. The method for preparing gel microspheres based on bubble generation and in-situ polymer deposition according to claim 1, characterized in that, The polyacrylamide gel is prepared using polyacrylamide or partially hydrolyzed polyacrylamide.

3. The method for preparing gel microspheres based on bubble generation and in-situ polymer deposition according to claim 2, characterized in that, The degree of hydrolysis of the partially hydrolyzed polyacrylamide is 10-30%.

4. The method for preparing gel microspheres based on bubble generation and in-situ polymer deposition according to claim 2, characterized in that, The polyacrylamide or partially hydrolyzed polyacrylamide has a molecular weight of 5-60 million.

5. The method for preparing gel microspheres based on bubble generation and in-situ polymer deposition according to claim 1, characterized in that, The Fenton-like system is an aqueous solution prepared from hydrogen peroxide and complexed iron in a molar ratio of (10.2~10.5):

1.

6. The method for preparing gel microspheres based on bubble generation and in-situ polymer deposition according to claim 5, characterized in that, The hydrogen peroxide is at least one of sodium percarbonate, percarbonamide, sodium perborate, calcium peroxide, and magnesium peroxide.

7. The method for preparing gel microspheres based on bubble generation and in-situ polymer deposition according to claim 5, characterized in that, The complexed iron is complexed with ferric ions using ethylenediaminetetraacetic acid salt, citrate, oxalate, tartrate, or gluconate, wherein the ferric ions are divalent or trivalent.

8. The method for preparing gel microspheres based on bubble generation and in-situ polymer deposition according to claim 1, characterized in that, The mass ratio of the polyacrylamide gel to the Fenton-like system is 1:(5-12).

9. The method for preparing gel microspheres based on bubble generation and in-situ polymer deposition according to claim 1, characterized in that, The reaction temperature is 60-80℃, and the reaction time is 4-24h.

10. Gel microspheres, characterized in that, The gel microspheres are prepared according to any one of claims 1-9, based on bubble generation and in-situ polymer deposition. The microspheres are hollow inside and the shell is composed of polyacrylamide degradation products. The viscosity of the degradation products has an average molecular weight of 5 to 2 million. The microspheres have a diameter of 10-50 μm, a shell thickness of 1-5 μm, and a shell compressive strength of 2-5 MPa.

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