A core-shell abnormal PEGDA porous microsphere based on a low-boiling point pore-forming agent, a preparation method and application thereof

Abstract

This invention discloses a method for preparing core-shell shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent: An aqueous solution containing a photoinitiator is emulsified with a low-boiling-point hydrophobic liquid pore-forming agent and a surfactant to obtain an aqueous phase solution; an oil phase solution is prepared; the aqueous and oil phase solutions are injected into the aqueous and oil phase microchannels of a droplet microfluidic chip, respectively, using an external pump to generate microdroplets; the microdroplets are cured by ultraviolet irradiation within a flexible tube channel to obtain PEGDA microspheres; the PEGDA microspheres are dried to obtain core-shell shaped PEGDA porous microspheres. This invention also discloses the core-shell shaped PEGDA porous microspheres obtained by the above preparation method and their applications in drug delivery, catalyst loading, coatings, organic pollutant adsorbents, acoustic functional materials, or biosensors. The preparation method provided by this invention enables low-cost, batch preparation of monodisperse micron-sized PEGDA porous microspheres, and the obtained PEGDA porous microspheres exhibit a core-shell shaped pore morphology.

Description

Technical Field

[0001] This invention belongs to the field of droplet microfluidics technology, and specifically relates to a core-shell irregularly shaped PEGDA porous microsphere based on a low-boiling-point pore-forming agent, its preparation method, and its application. Background Technology

[0002] Polyethylene glycol diacrylate (PEGDA) is a hydrogel material that can be rapidly photopolymerized at room temperature. It has advantages such as low toxicity, good biocompatibility, easy chemical modification, and a wide molecular weight range. Due to its porous structure, PEGDA porous microspheres possess some special properties, such as low density, high specific surface area, good adsorption, and good light or sound scattering. It is widely used in drug delivery, catalyst loading, biosensing, cosmetics, coatings, organic pollutant adsorbents, and acoustic functional materials.

[0003] Traditional methods for preparing PEGDA porous microspheres mainly involve emulsion polymerization, dispersion polymerization, and suspension polymerization combined with solid pore-forming agents (such as micro / nano particles of sparingly soluble carbonates and bicarbonates). Emulsion polymerization is primarily used to prepare nano- and submicron-sized particles, dispersion polymerization generally prepares monodisperse particles ranging from a few micrometers to tens of micrometers, and suspension polymerization is often used to prepare large-diameter particles and porous microspheres ranging from tens of micrometers to several millimeters. However, it can be observed that the surfaces of PEGDA microspheres obtained by traditional methods are relatively smooth, based on the principle of minimum surface energy; smooth microspheres have the lowest external surface area. Furthermore, the pore size of PEGDA porous microspheres obtained by traditional methods is almost entirely comparable to the size of the solid pore-forming agent particles (generally less than a few micrometers). To further increase the pore size of PEGDA porous microspheres, the size of the solid pore-forming agent particles must be increased. However, larger solid pore-forming agent particles are less able to mix uniformly with the PEGDA precursor solution, thus limiting the increase in pore size of the PEGDA porous microspheres. To meet diverse application needs, specific requirements are often placed on the morphology of PEGDA microspheres. For example, increasing the surface roughness of the microspheres can significantly increase their external surface area, thereby enhancing contact during use. Other requirements include modifying the size, shape, and distribution of pores within the microspheres as needed. However, these specially morphological PEGDA microspheres are often not obtained through a single-step polymerization process using traditional methods.

[0004] Droplet microfluidics enables the flow control of droplets in microchannels, providing a novel platform for the controllable design and precise manipulation of size, morphology, and functional properties in microdroplet generation. However, there are no reports on how to prepare PEGDA microspheres with special morphologies using droplet microfluidics. Summary of the Invention

[0005] The purpose of this invention is to provide a core-shell shaped PEGDA porous microsphere based on a low-boiling-point pore-forming agent and its preparation method, which can realize the low-cost batch preparation of monodisperse micron-sized PEGDA porous microspheres, and the pore morphology of the obtained PEGDA porous microspheres exhibits a core-shell shaped structure.

[0006] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0007] A method for preparing core-shell shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent, the method comprising:

[0008] (1) A PEGDA aqueous solution containing a photoinitiator was emulsified with a low-boiling-point hydrophobic liquid pore-forming agent and a surfactant to obtain a dispersed phase / aqueous phase solution.

[0009] (2) Prepare a continuous phase / oil phase solution;

[0010] (3) The aqueous solution and the oil solution are injected into the aqueous microchannel and the oil microchannel of the droplet microfluidic chip respectively by an external pump to generate microdroplets;

[0011] (4) Microdroplets are cured by ultraviolet irradiation in the tube channel to obtain PEGDA microspheres;

[0012] (5) After drying the PEGDA microspheres, core-shell shaped PEGDA porous microspheres are obtained.

[0013] The preparation method provided by this invention utilizes a low-boiling-point hydrophobic liquid as a pore-forming agent (n-pentane, methyl formate, or ethyl acetate, with a boiling point below 80°C at normal pressure, and hydrophobic). The low-boiling-point hydrophobic liquid is emulsified with an aqueous solution of PEGDA to create microdroplets of PEGDA aqueous solution encapsulating numerous low-boiling-point hydrophobic liquid microdroplets. After PEGDA is cured by ultraviolet light, the low-boiling-point hydrophobic liquid microdroplets remain in a liquid state. After high-temperature drying, the low-boiling-point hydrophobic liquid microdroplets inside the PEGDA microspheres vaporize and escape. The vaporization of the low-boiling-point hydrophobic liquid microdroplets on the shallow surface of the PEGDA microspheres results in a uniform and dense distribution of hemispherical pits on the surface of the PEGDA microspheres. The vaporization of the low-boiling-point hydrophobic liquid microdroplets inside the PEGDA microspheres results in alternating river-like pores and partially spherical closed pores within the PEGDA microspheres, thereby forming core-shell heteromorphic porous PEGDA microspheres.

[0014] In step (1), the low-boiling-point hydrophobic liquid pore-forming agent is selected from n-pentane, methyl formate, or ethyl acetate; the average molecular weight of PEGDA is 400-700; the photoinitiator is selected from 2-hydroxy-2-methyl-1-phenylpropanone or 1-hydroxycyclohexylbenzophenone; the surfactant is selected from Span80 or Span85; and the emulsification method is selected from an ultrasonic pulverizer or a high-speed homogenizer.

[0015] The volume ratio of the low-boiling-point hydrophobic liquid pore-forming agent to the PEGDA aqueous solution is 1:5 to 1:1; the volume fraction of PEGDA in the PEGDA aqueous solution is 8% to 50%; and the proportion of the photoinitiator in the aqueous phase is 1% to 3 wt%.

[0016] In step (2), the oil phase is selected from silicone oil, liquid paraffin or n-hexadecane, and contains 1 to 6 t.% surfactant, which is Span 60 or Span 80.

[0017] In step (3), the external pump is selected from a micro-injection pump or a micro-pressure peristaltic pump; the microfluidic chip includes a T-shaped chip, a flow focusing chip or a coaxial flow chip, a PDMS chip or a metal droplet generator.

[0018] In step (3), the radii of the aqueous phase microchannel and the oil phase microchannel in the microfluidic chip are 50 to 500 μm, the flow rates of the aqueous phase and the oil phase are independently 2 to 200 μL / min, and the ratio of the aqueous phase flow rate to the oil phase flow rate is 1:(1 to 10).

[0019] In step (4), the intensity of ultraviolet light received by each microdroplet is 30–80 mW / cm². 2 The illumination time is 3 to 40 seconds.

[0020] Preferably, the method for preparing the core-shell shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent includes the following steps:

[0021] Step 1: Prepare the continuous phase / oil phase solution: Add oil (silicone oil, liquid paraffin or n-hexadecane) and 1-6 vt.% Span series surfactant (Span60 or Span80) to a beaker, stir until completely dissolved to obtain a continuous phase solution.

[0022] Step 2: Preparation of dispersed / aqueous phase solution: Add 8–50 vt.% polyethylene glycol diacrylate (PEGDA) (average molecular weight 400–700), 2–5 vt.% photoinitiator (2-hydroxy-2-methyl-1-phenylpropanone or 1-hydroxycyclohexylbenzophenone), and an appropriate amount of deionized water to a brown glass bottle, and stir magnetically for 20–40 minutes to obtain a PEGDA aqueous solution; then add the PEGDA aqueous solution and a low-boiling-point hydrophobic liquid pore-forming agent (n-pentane, methyl formate, or ethyl acetate) to the solution. The solution (with a boiling point below 80℃ under normal pressure and hydrophobic) is prepared in a brown glass bottle at a volume ratio of 5:1 to 1:1. Then, 1 to 3 wt.% of Span series surfactants (Span 80 or Span 85) is added. The mixture is then homogenized using an ultrasonic pulverizer (100W to 600W, 0.5 to 2 minutes) or a high-speed homogenizer (8000 to 30000 rpm, 1 to 5 minutes). Finally, the mixture is magnetically stirred for 15 to 60 minutes (200 to 800 rpm) to obtain the dispersed phase solution.

[0023] Step 3: Constructing a droplet microfluidic platform for microsphere fabrication: The droplet microfluidic platform mainly consists of an external pump, a microfluidic chip, a UV lamp, a microscope, a collection bottle, a syringe, and tubing. The external pump is selected from a micro-injection pump or a micro-pressure peristaltic pump. The microfluidic chip includes a T-shaped chip, a flow-focusing chip, or a coaxial flow chip (PDMS chip) or a metal droplet generator. The radii of the aqueous and oil microchannels in the microfluidic chip are 50–500 μm, and the flow rates of the aqueous and oil phases are independently 2–200 μL / min, with a flow rate ratio of 1:(1–10). Aspirate both the dispersed and continuous phase solutions into 10 mL syringes, and fix the syringes onto a microinjection pump. Adjust the pump parameters (continuous phase flow rate: 20–200 μL / min; dispersed phase flow rate: 2–50 μL / min; dispersed phase flow rate to continuous phase flow rate: 1:(1–10)). Mount the droplet microfluidic chip onto a fixture. Connect the chip inlet to the needle via a tubing, and connect the outlet tubing to a collection bottle. Position the outlet tubing at the same level as the droplet microfluidic chip. Install a UV lamp (365 nm) at the tubing channel, ensuring the UV light intensity at the tubing channel is 30–80 mW / cm². 2 The illumination time is 3-40 seconds, and the outlet hose is connected to the collection bottle.

[0024] Step 4: Microsphere collection, pore formation, and post-processing: Adjust the flow rates of the dispersed and continuous phases to ensure uniform microdroplet generation. The microdroplets solidify into microspheres under UV irradiation. Collect the solution containing PEGDA microspheres in a microsphere collection bottle. Wash and filter the collected PEGDA microspheres with deionized water and anhydrous ethanol, repeating the process multiple times until the washing liquid is clear. Then, dry the PEGDA microspheres in an oven at 45–80℃ for 6–10 hours to obtain core-shell shaped PEGDA porous microspheres.

[0025] The present invention also provides a core-shell shaped PEGDA porous microsphere based on a low-boiling-point pore-forming agent obtained according to the above preparation method.

[0026] The PEGDA porous microspheres provided by this invention are prepared by droplet microfluidics combined with a low-boiling-point hydrophobic liquid pore-forming agent.

[0027] Furthermore, the particle size of the PEGDA porous microspheres is 100–450 μm; the pore morphology of the PEGDA porous microspheres exhibits a core-shell heterogeneous shape, with uniformly and densely distributed hemispherical pits on the outer surface, and alternating river-like pores and partially spherical closed pores inside; wherein, the particle size of the PEGDA porous microspheres is 100–450 μm, the hemispherical pits have a size of 5–20 μm, the river-like pores have a size of 3–25 μm, and the spherical closed pores have a size of 1–5 μm.

[0028] The present invention also provides an application of the above-mentioned core-shell irregular PEGDA porous microspheres in the fields of drug delivery, catalyst loading, coatings, organic pollutant adsorbents, acoustic functional materials or biosensors.

[0029] Compared with the prior art, the present invention has the following superior effects:

[0030] The preparation method proposed in this invention can balance monodispersity, size uniformity, pore morphology control of porous microspheres, mechanical properties, and preparation difficulty, and achieve low-cost batch preparation of monodisperse micron-sized core-shell PEGDA porous microspheres. It has broad application prospects in drug delivery, catalyst loading, coatings, organic pollutant adsorbents, acoustic functional materials, and biosensors. Attached Figure Description

[0031] Figure 1 The image shown is a scanning electron microscope (SEM) image of the core-shell PEGDA porous microspheres based on a low-boiling-point pore-forming agent prepared in the examples.

[0032] Figure 2 The image shown is a scanning electron microscope (SEM) image of a partial cross-section of the core-shell PEGDA porous microspheres based on a low-boiling-point pore-forming agent prepared in the example.

[0033] Figure 3The solid PEGDA microspheres prepared in the comparative example are shown. Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be described in detail below with reference to embodiments, comparative examples, and accompanying drawings. It should be noted that the following embodiments are only used to explain and illustrate this invention and are not intended to limit this invention.

[0035] Example

[0036] The preparation method of core-shell irregular PEGDA porous microspheres based on low-boiling-point pore-forming agents in this embodiment includes the following steps:

[0037] (1) Preparation of continuous phase / oil phase solution: Add liquid paraffin and 3 t.% Span80 surfactant to a beaker and stir until completely dissolved to obtain continuous phase solution.

[0038] (2) Preparation of dispersed / aqueous solution: Add 20 vt.% polyethylene glycol diacrylate (PEGDA) (average molecular weight 600), 2 vt.% photoinitiator (2-hydroxy-2-methyl-1-phenylpropanone), and an appropriate amount of deionized water to a brown glass bottle, and stir magnetically for 30 minutes to obtain an aqueous PEGDA solution. Then, prepare the aqueous PEGDA solution and a low-boiling-point hydrophobic liquid pore-forming agent (n-pentane, boiling point 36℃ at normal pressure, hydrophobic) in a brown glass bottle at a volume ratio of 5:1, add 3 vt.% Span85 surfactant, and mix evenly using a high-speed homogenizer (10000 rpm, 2 minutes), and then stir magnetically for 30 minutes (600 rpm) to obtain the dispersed phase solution.

[0039] (3) Construction of droplet microfluidic technology for microsphere preparation: The droplet microfluidic technology platform mainly consists of a micro-injection pump, a T-shaped metal droplet generator (minimum channel radius of 100 μm), an ultraviolet lamp, a microscope, a collection bottle, a syringe, and tubing. The dispersed phase and continuous phase solutions are respectively drawn into 10 mL syringes, which are then fixed to the micro-injection pump. The pump parameters are adjusted (continuous phase flow rate 100 μL / min, dispersed phase flow rate 10 μL / min). The droplet microfluidic chip is mounted on a fixture. The chip inlet is connected to the needle via a tubing, and the outlet tubing is connected to the collection bottle. The outlet tubing is positioned at the same level as the droplet microfluidic chip. An ultraviolet lamp (365 nm) is installed at the tubing channel, with the ultraviolet light intensity at the tubing channel being 40 mW / cm². 2 The illumination time is 12 seconds, and the outlet hose is connected to the microsphere collection bottle.

[0040] (4) Microsphere collection, microsphere pore formation and post-processing: Adjust the flow rates of the dispersed phase and the continuous phase to ensure uniform generation of microdroplets. The microdroplets are solidified into microspheres under ultraviolet light irradiation. The solution containing PEGDA microspheres is collected in the microsphere collection bottle. The collected PEGDA microspheres are washed and filtered with deionized water and anhydrous ethanol, and the process is repeated 3 times. Then, the PEGDA microspheres are dried in a 45℃ oven for 8 hours to obtain core-shell shaped PEGDA porous microspheres.

[0041] The scanning electron microscope (SEM) image of the core-shell heteromorphic PEGDA porous microspheres prepared in this embodiment based on a low-boiling-point pore-forming agent is shown below. Figure 1 As shown, its particle size is approximately 330 μm, and from Figure 1 As can be seen, the outer surface of the core-shell heteromorphic PEGDA porous microspheres is composed of uniformly and densely distributed hemispherical pits with a pit size of 5–15 μm.

[0042] Scanning electron microscopy (SEM) of a portion of the cross-section of the core-shell heteromorphic PEGDA porous microspheres prepared in this embodiment, based on a low-boiling-point pore-forming agent, is shown below. Figure 2 As shown, from Figure 2 It can be seen that the interior of the core-shell heteromorphic PEGDA porous microspheres consists of alternating river-like pores and partially spherical closed pores: the scale of the river-like pores is 3 to 20 μm, and the scale of the spherical closed pores is 1 to 5 μm.

[0043] Comparative Example

[0044] Preparation of continuous phase / oil phase solution: Add liquid paraffin and 3 t.% Span 80 surfactant to a beaker and stir until completely dissolved to obtain a continuous phase solution.

[0045] Preparation of dispersed / aqueous solution: Add 20 vt.% polyethylene glycol diacrylate (PEGDA) (average molecular weight 600), 2 vt.% photoinitiator (2-hydroxy-2-methyl-1-phenylpropanone), and an appropriate amount of deionized water to a brown glass bottle, and stir magnetically for 30 minutes to obtain the dispersed solution.

[0046] The droplet microfluidic platform for microsphere fabrication was constructed using a micro-injection pump, a T-shaped metal droplet generator (minimum channel radius of 100 μm), a UV lamp, a microscope, a collection bottle, a syringe, and tubing. The dispersed and continuous phase solutions were drawn into 10 mL syringes, which were then fixed to the micro-injection pump. The pump parameters were adjusted (continuous phase flow rate 100 μL / min, dispersed phase flow rate 10 μL / min). The droplet microfluidic chip was mounted on a fixture. The chip inlet was connected to the needle via a tubing, and the outlet tubing led into the collection bottle. The outlet tubing was positioned at the same level as the droplet microfluidic chip. A 365 nm UV lamp was installed at the tubing channel, with the UV light intensity at the channel set at 40 mW / cm².2 The illumination time is 12 seconds, and the outlet hose is connected to the microsphere collection bottle.

[0047] Microsphere collection, microsphere pore formation and post-processing: The flow rates of the dispersed phase and the continuous phase were adjusted to ensure uniform generation of microdroplets. The microdroplets were solidified into microspheres under UV irradiation. The solution containing PEGDA microspheres was collected in the microsphere collection bottle. The collected PEGDA microspheres were washed and filtered with deionized water and anhydrous ethanol, and the process was repeated 3 times. Then, the PEGDA microspheres were dried in a 45℃ oven for 8 hours to obtain solid PEGDA microspheres.

[0048] The PEGDA solid microspheres prepared in this comparative example are as follows: Figure 3 As shown, from Figure 3 It can be seen that its outer surface is very smooth and its particle size is about 300μm.

[0049] The specific embodiments described above illustrate the technical solution and beneficial effects of the present invention in detail. It should be understood that the above description is only the most preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, additions, and equivalent substitutions made within the scope of the principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing core-shell irregularly shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent, characterized in that, The preparation method includes: (1) A dispersed phase / aqueous phase solution was obtained by emulsifying an aqueous solution of PEGDA containing a photoinitiator with a low-boiling-point hydrophobic liquid pore-forming agent and a surfactant. (2) Prepare a continuous phase / oil phase solution; (3) The aqueous solution and the oil solution are injected into the aqueous microchannel and the oil microchannel of the droplet microfluidic chip respectively by an external pump to generate microdroplets; (4) Microdroplets are cured by ultraviolet irradiation in the tube channel to obtain PEGDA microspheres; (5) When PEGDA is cured by ultraviolet light, the low-boiling-point hydrophobic liquid microdroplets are still in a liquid state. After the PEGDA microspheres are dried at high temperature, the low-boiling-point hydrophobic liquid microdroplets inside the microspheres are vaporized and escaped. After the low-boiling-point hydrophobic liquid microdroplets on the shallow surface of the PEGDA microspheres are vaporized, hemispherical pits are evenly and densely distributed on the surface of the PEGDA microspheres. After the low-boiling-point hydrophobic liquid microdroplets inside the PEGDA microspheres are vaporized, river-like cracks and some spherical closed pores are distributed alternately inside the PEGDA microspheres, thus forming core-shell heteromorphic PEGDA porous microspheres.

2. The method for preparing core-shell irregularly shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent according to claim 1, characterized in that, In step (1), the low-boiling-point hydrophobic liquid pore-forming agent is selected from n-pentane, methyl formate, or ethyl acetate; the average molecular weight of PEGDA is 400-700; the photoinitiator is selected from 2-hydroxy-2-methyl-1-phenylpropanone or 1-hydroxycyclohexylbenzophenone; the surfactant is selected from Span80 or Span85; and the emulsification method is selected from an ultrasonic pulverizer or a high-speed homogenizer.

3. The method for preparing core-shell irregularly shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent according to claim 2, characterized in that, The volume ratio of the low-boiling-point hydrophobic liquid pore-forming agent to the PEGDA aqueous solution is 1:5 to 1:1; the volume fraction of PEGDA in the PEGDA aqueous solution is 8% to 50%; and the proportion of the photoinitiator in the aqueous phase is 1% to 3% (vt.%).

4. The method for preparing core-shell irregularly shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent according to claim 1, characterized in that, In step (2), the oil phase is selected from silicone oil, liquid paraffin or n-hexadecane, and contains 1 to 6 vt.% surfactant, which is Span60 or Span80.

5. The method for preparing core-shell irregularly shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent according to claim 1, characterized in that, In step (3), the external pump is selected from a micro-injection pump or a micro-pressure peristaltic pump; the microfluidic chip is selected from a T-type chip, a flow focusing chip or a coaxial flow chip, a PDMS chip or a metal droplet generator.

6. The method for preparing core-shell irregularly shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent according to claim 1, characterized in that, In step (3), the radius of the aqueous phase microchannel and the oil phase microchannel in the microfluidic chip is 50~500μm, the flow rate of the aqueous phase and the flow rate of the oil phase are independently 2~200μL / min, and the ratio of the aqueous phase flow rate to the oil phase flow rate is 1:(1~10).

7. The method for preparing core-shell irregularly shaped PEGDA porous microspheres based on a low-boiling-point pore-forming agent according to claim 1, characterized in that, In step (4), the intensity of ultraviolet light received by each microdroplet is 30~80 mW / cm. 2 The illumination time is 3~40 s.

8. A core-shell shaped PEGDA porous microsphere based on a low-boiling-point pore-forming agent, obtained by the preparation method according to any one of claims 1-7.

9. The core-shell irregularly shaped PEGDA porous microspheres according to claim 8, characterized in that, The PEGDA porous microspheres have a particle size of 100-450 μm; the pore morphology of the PEGDA porous microspheres exhibits a core-shell heterogeneous shape, with uniformly and densely distributed hemispherical pits on the outer surface, and alternating river-like pores and some spherical closed pores inside; wherein, the particle size of the PEGDA porous microspheres is 100-450 μm, the hemispherical pits have a size of 5-20 μm, the river-like pores have a size of 3-25 μm, and the spherical closed pores have a size of 1-5 μm.

10. The application of the core-shell irregularly shaped PEGDA porous microspheres of claim 8 in drug delivery, catalyst loading, coatings, organic pollutant adsorbents, acoustic functional materials or biosensors.

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