High-loading mxene-encapsulated magnetic porous microcapsules for adsorption and methods of making and using the same

Abstract

The application discloses a high-loading MXene-encapsulated magnetic porous microcapsule for adsorption and a preparation method and application thereof, and belongs to the field of biomedical materials, and the preparation method comprises the following steps: in step one, a hydrogel precursor solution doped with magnetic nanoparticles is used as an external phase, and a MXene dispersion liquid is used as an inner phase, and a microfluidic coaxial electrospraying device is used to generate monodisperse core-shell droplets with uniform sizes; in step two, the monodisperse core-shell droplets prepared in step one are subjected to freezing pretreatment, and then are crosslinked with divalent metal ions, so that double gelation of the core layer and the shell layer is triggered, and hydrogel microspheres with a core-shell structure are obtained; and in step three, the hydrogel microspheres with the core-shell structure obtained in step two are subjected to freeze drying, and high-loading MXene-encapsulated magnetic porous microcapsules are obtained. The application has excellent blood compatibility and high adsorption capacity, and is outstanding in removing uremic toxins including creatinine, urea and uric acid, and is a kind of adsorbent which is both efficient and safe.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical materials and relates to an adsorption material, in particular to a high-load MXene-encapsulated magnetic porous microcapsule for adsorption, and a preparation method and application thereof. Background Art

[0002] Adsorption is an important separation and purification technology that plays an important role in the fields of chemical industry, environmental protection, biomedicine, etc. The adsorption process relies on adsorbents to remove harmful components or enrich beneficial components. In the past few decades, in order to achieve the above goals, various adsorption materials have been developed, including polymers, carbonaceous materials, metal-organic framework materials, etc. In addition, by adding magnetic elements, the adsorbent can have controllable mobility, which facilitates the collection of adsorbates and the recycling and reuse of the adsorbent. It is worth noting that the adsorbents involved in the biomedical field should have more comprehensive properties, especially biocompatibility. Therefore, higher requirements are placed on the composition and preparation method of the adsorbent. Therefore, it is still worth considering the development of new adsorbents that are both efficient and have good biosafety.

[0003] MXenes have attracted widespread attention due to their unique properties, such as their two-dimensional lamellar structure, high specific surface area, hydrophilicity, and abundant active sites. Like other layered materials, MXenes can embed water, organic molecules, or metal ions. Most importantly, MXenes have good biocompatibility, which opens up the possibility of adsorption in biological systems. However, the practical application of MXene as an adsorbent faces several challenges. On the one hand, pristine MXene nanosheets easily restack, resulting in a decrease in surface utilization. On the other hand, the construction of MXene-based hybrid systems faces the dilemma of low MXene content. Summary of the Invention

[0004] In response to the deficiencies in the prior art, the present invention provides a high-load MXene-encapsulated magnetic porous microcapsule for adsorption, as well as a preparation method and application thereof. A MXene dispersion is used as a core liquid and a hydrogel precursor solution doped with magnetic nanoparticles is used as a shell liquid. A microfluidic coaxial electrospray device is used to prepare high-load MXene-encapsulated magnetic porous microcapsules in one step. The high-load MXene-encapsulated magnetic porous microcapsules can be used to efficiently remove three types of uremic toxins, namely creatinine, urea and uric acid, and have satisfactory blood compatibility.

[0005] To achieve the above-mentioned object, the present invention provides a method for preparing high-load MXene-encapsulated magnetic porous microcapsules for adsorption, which has the following characteristics: comprising the following steps: step 1, using a hydrogel precursor solution doped with magnetic nanoparticles as the outer phase (shell liquid) and a MXene dispersion as the inner phase (core liquid), generating monodisperse core-shell droplets of uniform size by a microfluidic coaxial electrospray device; step 2, subjecting the monodisperse core-shell droplets prepared in step 1 to a freezing pretreatment, and then cross-linking them with divalent metal ions to induce double gelation of the core layer and the shell layer to obtain hydrogel microspheres with a core-shell structure; step 3, freeze-drying the hydrogel microspheres with a core-shell structure obtained in step 2 to obtain high-load MXene-encapsulated magnetic porous microcapsules; wherein the hydrogel precursor in step 1 is a viscous hydrogel precursor that can be cross-linked with divalent metal ions and is not positively charged, and the divalent metal ions in step 2 are divalent metal ions that can cross-link with the hydrogel precursor in step 1.

[0006] By changing the preparation parameters of the monodisperse core-shell droplets in step 1, the size, morphology or core-shell component ratio of the final high-loading MXene-encapsulated magnetic porous microcapsules can be adjusted.

[0007] Furthermore, the present invention provides a method for preparing high-load MXene-encapsulated magnetic porous microcapsules for adsorption, which may also have the following characteristics: wherein the hydrogel precursor in step one is alginate, and the divalent metal ion in step two is barium ion.

[0008] Furthermore, the present invention provides a method for preparing high-load MXene-encapsulated magnetic porous microcapsules for adsorption, which may also have the following characteristics: wherein, the specific method of step 2 is: collecting the monodisperse core-shell droplets prepared in step 1 in a container filled with liquid nitrogen, and immediately pouring a divalent metal ion solution into it after the liquid nitrogen evaporates, thereby inducing double gelation of the core layer and the shell layer to obtain hydrogel microspheres with a core-shell structure.

[0009] Furthermore, the present invention provides a method for preparing high-load MXene-encapsulated magnetic porous microcapsules for adsorption, which may also have the following characteristics: wherein, in step 2, the cross-linking time is 20 to 40 minutes.

[0010] Furthermore, the present invention provides a method for preparing high-load MXene-encapsulated magnetic porous microcapsules for adsorption, which may also have the following characteristics: wherein, in step 1, in the hydrogel precursor solution doped with magnetic nanoparticles, the concentration of the magnetic nanoparticles relative to the hydrogel precursor solution is 0.5-2 wt%, and the concentration of the hydrogel precursor solution is 1.5-3 wt%; the concentration of the MXene dispersion is 30-45 mg / ml.

[0011] Furthermore, the present invention provides a method for preparing high-load MXene-encapsulated magnetic porous microcapsules for adsorption, which may also have the following characteristics: wherein, in step 2, the concentration of the divalent metal ion solution is 0.5 to 2 wt%.

[0012] Furthermore, the present invention provides a method for preparing high-load MXene-encapsulated magnetic porous microcapsules for adsorption, which may also have the following characteristics: wherein, in step 2, the container is a container made of polytetrafluoroethylene or tin foil.

[0013] Furthermore, the present invention provides a method for preparing high-load MXene-encapsulated magnetic porous microcapsules for adsorption, which may also have the following characteristics: wherein, in step 1, the internal phase flow rate is 0.5 to 4 ml / h, the external phase flow rate is 1 to 6 ml / h, the receiving distance is 4 to 10 cm, and the voltage is +4 to +10 kV.

[0014] The present invention also provides a high-load MXene-encapsulated magnetic porous microcapsule for adsorption prepared by the above preparation method.

[0015] The present invention also provides the use of high-load MXene-encapsulated magnetic porous microcapsules for adsorption in the preparation of products for the adsorption of uremic toxins. Uremic toxins include creatinine, urea, and uric acid. These high-load MXene-encapsulated magnetic porous microcapsules, with their robust porous biomass shell and three-dimensional MXene core, exhibit excellent scavenging capabilities and satisfactory blood compatibility, making them highly effective and safe adsorbents.

[0016] The beneficial effects of the present invention are:

[0017] First, the present invention utilizes microfluidic technology to fabricate core-shell microcapsules, effectively encapsulating active ingredients while maintaining overall structural integrity and enabling their efficacy. The microfluidic coaxial electrospray device features a simple process, minimal assembly steps, and a streamlined channel. The size, morphology, and shell thickness of the gelled core-shell microcapsules can be adjusted through controlled manufacturing parameters, offering flexible operation.

[0018] 2. The present invention designs a MXene microcarrier with a core-shell structure, in which the biomass shell derived from hydrogel precursors such as alginate provides strong support for the MXene core and prevents leakage during use, ensuring biosafety. At the same time, it can also achieve a high loading distribution of the MXene active components to optimize the adsorption effect.

[0019] 3. The present invention induces the self-assembly of MXene nanosheets through the gelation between MXene and divalent metal ions such as barium ions to form a three-dimensional network structure, thereby avoiding the accumulation of MXene nanosheets and improving the surface utilization.

[0020] 4. The present invention adopts a reasonable porous structure design in the microcapsule, which can facilitate the diffusion and adsorption of molecules. Specifically, the present invention forms a macroporous structure in the biomass shell through liquid nitrogen freezing pretreatment, which helps the target molecules to diffuse and be adsorbed between the MXene core and the external environment.

[0021] 5. The present invention incorporates magnetic nanoparticles into the shell of the microcapsule, so that the microcapsule has controllable movement ability, thereby achieving flexible separation.

[0022] 6. The high-load MXene-encapsulated magnetic porous microcapsules prepared by the present invention have excellent blood compatibility and outstanding performance in adsorbing uremic toxins. They are a potential adsorbent for artificial kidney or dialysate regeneration. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 Schematic diagram of the preparation process of the high-load MXene-encapsulated magnetic porous microcapsules of the present invention;

[0024] Figure 2 is a diagram of a microfluidic coaxial electrospray device, wherein a is a physical diagram of the microfluidic coaxial electrospray device, and b is an enlarged view of the coaxial nozzle;

[0025] Figure 3 : are optical micrographs of high-load MXene-encapsulated magnetic porous microcapsules prepared in the present invention, wherein a is a microcapsule prepared at an internal phase flow rate of 0.5 ml / h, b is a microcapsule prepared at an internal phase flow rate of 1.0 ml / h, c is a microcapsule prepared at an internal phase flow rate of 2 ml / h, and d is a microcapsule prepared at an internal phase flow rate of 4 ml / h;

[0026] Figure 4 3 is a scanning electron microscope image of a high-load MXene-encapsulated magnetic porous microcapsule prepared in the present invention, wherein a is a complete microcapsule, b is a magnified view of the corresponding surface, c is a cross-section of the microcapsule, and d is a magnified view of the core layer;

[0027] Figure 5 The adsorption kinetic curves of uremic toxins by the high-load MXene-encapsulated magnetic porous microcapsules prepared by the present invention are shown in FIG. 1 , wherein a is the adsorption kinetic curve for creatinine, b is the adsorption kinetic curve for urea, and c is the adsorption kinetic curve for uric acid.

[0028] Figure 6This is a photo of the magnetic responsive separation of high-load MXene-encapsulated magnetic porous microcapsules prepared by the present invention; Figure 7 This is the blood compatibility evaluation of the high-load MXene-encapsulated magnetic porous microcapsules prepared by the present invention, where a and b are coagulation tests, and c is a hemolysis test. DETAILED DESCRIPTION

[0029] The present invention will be further described below with reference to specific embodiments and accompanying drawings.

[0030] like Figure 1 As shown, this embodiment provides a high-load MXene-encapsulated magnetic porous microcapsule for adsorption, and the preparation method thereof comprises the following steps:

[0031] Step 1: Assemble the microfluidic coaxial electrospray device: Figure 2 As shown, the microfluidic coaxial electrospray device consists of coaxially nested external and internal capillaries. The outlet of the internal capillary must be flush with the outlet of the external capillary, while ensuring that the internal capillary does not block the inlet of the external capillary. The internal capillary is a single-channel capillary with an inner diameter of 0.58 mm and an outer diameter of 1 mm, drawn using a laboratory spray gun to form an outlet diameter of approximately 120 μm. The external capillary is a single-channel capillary with an inner diameter of 0.75 mm and an outer diameter of 1 mm, drawn using a tube puller to form an outlet diameter of approximately 350 μm.

[0032] Preparation of monodisperse core-shell droplets: Sodium alginate solution doped with ferroferric oxide nanoparticles (the concentration of the sodium alginate solution is 3wt%, and the concentration of ferroferric oxide nanoparticles relative to the sodium alginate solution is 1wt%) is used as the outer phase (i.e., shell liquid), and 40mg / ml of MXene dispersion is used as the inner phase (i.e., core liquid), and a microfluidic coaxial electrospray device is used to generate monodisperse core-shell droplets of uniform size. Specifically, the inner phase fluid and the outer phase fluid are extracted separately with a syringe and placed on a syringe pump. The syringe is connected to the microfluidic coaxial electrospray device through a polyethylene tube. After setting the flow rate of the inner phase fluid and the outer phase fluid on the syringe pump control panel, the syringe pump is started. When the inner phase fluid and the outer phase fluid meet on the outlet side, the inner phase is wrapped by the outer phase to form a core-shell co-flow. By applying an electric field stimulation, these co-flows will break through the limitation of surface tension and be ejected from the nozzle to form a core-shell droplet flow. Among them, the inner phase flow rate is 0.5~4ml / h, the outer phase flow rate is 1~6ml / h, the receiving distance is 4~10cm, and the voltage is +4~+10KV.

[0033] Step 2: Collect the uniformly sized, monodisperse core-shell droplets prepared in Step 1 in a fixed container filled with liquid nitrogen. After the liquid nitrogen evaporates, immediately add a 1 wt% barium chloride solution to cause the shell and core liquids to gel simultaneously, forming hydrogel microspheres with a core-shell structure.

[0034] Step 3: After collection, the hydrogel microspheres are washed with deionized water to remove excess barium ions. After freeze-drying, high-load MXene-encapsulated magnetic porous microcapsules are finally obtained.

[0035] In this embodiment, sodium alginate can also be other hydrogel precursors, and barium chloride can correspondingly be other divalent metal ion salts, as long as the following conditions are met: the hydrogel precursor in step 1 is viscous, capable of cross-linking with divalent metal ions, and non-positively charged, and the divalent metal ions in step 2 are divalent metal ions capable of cross-linking with the hydrogel precursor in step 1. For example, the hydrogel precursor can also be sodium carboxymethylcellulose, and the corresponding divalent metal ion salt can be barium chloride. Similarly, the ferrosoferric oxide nanoparticles can also be other magnetic nanoparticles.

[0036] The external phase flow rate was fixed at 2 ml / h, the receiving distance was 6 cm, the voltage was +6KV, and the internal phase flow rate was adjusted to 0.5 mL / h, 1.0 mL / h, 2.0 mL / h, and 4.0 mL / h in sequence. The optical microscopy images of the high-load MXene-encapsulated magnetic porous microcapsules were shown in Figure 2. Figure 3 As shown. Figure 3 As can be seen, in the resulting high-MXene-loaded magnetic porous microcapsules, the transparent area is shrinking, the black area is expanding, and the overall microcapsule size is gradually increasing. This process indicates that the proportion of MXene in the microcapsule is gradually increasing. In particular, when the internal phase flow rate reaches 4 ml / h, the MXene almost fills the entire chamber. Therefore, by adjusting the internal and external flow rate ratio, high MXene loading can be achieved.

[0037] The prepared high-load MXene-encapsulated magnetic porous microcapsules were observed under a scanning electron microscope. Figure 4 As shown. Figure 4 As can be seen, the magnetic porous microcapsules encapsulated with high MXene loading are spherical, with a porous shell and a three-dimensional cross-linked core. The porous structure in the shell can be attributed to the template traces left by the dendritic ice crystals formed during the freezing pretreatment process. This porous structure facilitates the diffusion and adsorption of target molecules. The three-dimensional network structure of the core layer is caused by gelation triggered by divalent barium ions. Zooming in on the core reveals the random pores formed by the MXene nanosheets. This three-dimensional network effectively prevents the restacking of the MXene nanosheets, greatly improving surface utilization.

[0038] The high-load MXene-encapsulated magnetic porous microcapsules of the present invention are used for adsorbing uremic toxins.

[0039] Test the adsorption kinetics curve of high-load MXene-encapsulated magnetic porous microcapsules: First, three uremic toxin solutions were prepared respectively, in which the concentration of creatinine solution was 100 mg / L, the concentration of urea solution was 300 mg / L, and the concentration of uric acid solution was 50 mg / L. Subsequently, high-load MXene-encapsulated magnetic porous microcapsules (7 mg) prepared under different internal phase flow rate conditions (0.5 ml / h, 1.0 ml / h, 2.0 ml / h, 4.0 ml / h) were added to 10 ml of the above three uremic toxin solutions and shaken at 37 ° C (150 rpm). Every 30 minutes, 200 μl of supernatant was taken and the residual concentration was determined by UV-visible spectrophotometer. At the same time, an equal volume of blank solvent (deionized water) was added to the corresponding solution to keep the solution volume constant. The absorbance wavelengths for creatinine and uric acid were 234 nm and 287 nm respectively; after the reaction of urea with p-dimethylaminobenzaldehyde, the residual concentration was measured at 426 nm. The adsorption capacity was calculated based on the residual concentration and the kinetic curve was drawn. The results are shown in Figure 2. Figure 5 As shown. Figure 5 It can be seen that the high-load MXene-encapsulated magnetic porous microcapsules have excellent adsorption performance for these three toxins. When the internal phase flow rate increases from 0.5ml / h to 4ml / h, the maximum adsorption capacity of the corresponding microcapsules also maintains an increasing trend, verifying the key adsorption role of MXene in the microcapsules.

[0040] A magnet was placed on one side of the uremic toxin solution containing high-load MXene-encapsulated magnetic porous microcapsules. Thanks to the magnetic response properties of the microcapsules, the microcapsules could be easily collected by the magnet, e.g. Figure 6 shown.

[0041] Blood compatibility evaluation of high-load MXene-encapsulated magnetic porous microcapsules:

[0042] 1. In vitro coagulation test: A fully automatic coagulation analyzer was used to measure three coagulation indices, namely prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT), to evaluate coagulation performance.

[0043] (1) Effect of MXene content in microcapsules on coagulation time: First, microcapsules prepared under different internal phase flow rate conditions (0.5 ml / h, 1.0 ml / h, 2.0 ml / h, 4.0 ml / h) were incubated in rabbit plasma at a dosage of 2 mg / ml for 30 min. After taking 300 μl of the supernatant from each sample, the coagulation time was measured on a coagulation analyzer using the corresponding detection kit. For comparison, a plasma sample without microcapsules was used as a control group. The results are shown in Figure 2. Figure 7 As shown in (a), compared with the control group, the three coagulation indicators did not decrease, meeting the coagulation requirements.

[0044] (2) Effect of microcapsule dosage on coagulation time: Taking microcapsules prepared under the condition that the internal phase flow rate and the external phase flow rate are both 2 ml / h as an example, microcapsules with different dosages (2 mg / ml, 4 mg / ml, 6 mg / ml, 8 mg / ml) were placed in rabbit plasma and incubated for 30 min, and then the supernatant was taken to measure the coagulation time. The results are shown in Figure 2. Figure 7 As shown in b, the increase in microcapsule dosage does not promote coagulation and meets the coagulation requirements.

[0045] 2. In vitro hemolysis test: The hemolysis rate can be calculated by detecting the amount of hemoglobin released in the supernatant.

[0046] Take fresh rabbit blood, centrifuge at 3500rpm for 10 minutes, wash it 3 times with PBS buffer, and then dilute the red blood cells 100 times with PBS buffer for later use. Add microcapsules (1mg) prepared under different internal phase flow rate conditions (0.5ml / h, 1.0ml / h, 2.0ml / h, 4.0ml / h) to 1ml red blood cell suspension, incubate at 37℃ for 2h, take the supernatant after centrifugation, and measure the absorbance value at 545nm with an enzyme marker. For comparison, PBS buffer and deionized water were used as negative and positive controls, respectively. The results are as follows: Figure 7 As shown in Figure c, compared with the positive control, no obvious red color was observed in the high-load MXene-encapsulated magnetic porous microcapsules. At the same time, all calculated hemolysis rates were below 1%, far below the clinical standard (5%), further confirming the good blood compatibility of the microcapsules.

[0047] The present invention uses a microfluidic coaxial electrospray device to continuously and stably generate core-shell droplets composed of a MXene dispersion as the core and a hydrogel precursor solution doped with magnetic nanoparticles as the shell. Through freeze pretreatment and rapid crosslinking induced by divalent metal ions, magnetic porous microcapsules with a core-shell structure are obtained. These microcapsules have a biomass shell, which provides strong support for the MXene core. Consequently, they exhibit high MXene loading and sufficient biosafety. Furthermore, the MXene nanosheets form a three-dimensional network structure through metal ion-induced gelation, thus avoiding sheet stacking and significantly improving surface utilization. Furthermore, freeze pretreatment of the microcapsules during the preparation process creates a macroporous structure within the shell, which facilitates the diffusion and adsorption of target molecules. The high-load MXene-encapsulated magnetic porous microcapsules prepared by this invention exhibit excellent blood compatibility and high adsorption capacity, and are particularly effective in removing uremic toxins, including creatinine, urea, and uric acid. Due to the doping of magnetic nanoparticles, the microcapsules possess controllable mobility, enabling flexible separation without residue. This high-load MXene-encapsulated magnetic porous microcapsule manufactured based on microfluidic technology is a new type of adsorbent that is both efficient and safe, and is expected to play an important role in dialysis-related applications.

[0048] In the present invention, unless otherwise specified, the scientific and technical terms used herein have the meanings commonly understood by those skilled in the art. In addition, the reagents, materials and operating procedures used herein are those widely used in the corresponding fields.

[0049] Finally, it should be noted that the above descriptions are merely preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art will be able to modify the technical solutions described in the aforementioned embodiments or substitute equivalents for some of the technical features. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. Application of a high-load MXene-encapsulated magnetic porous microcapsule for adsorption in the preparation of a product for adsorbing uremic toxins, characterized in that: The preparation method of the high-load MXene-encapsulated magnetic porous microcapsules comprises the following steps: Step 1: Using a hydrogel precursor solution doped with magnetic nanoparticles as the outer phase and a MXene dispersion as the inner phase, monodisperse core-shell droplets are generated using a microfluidic coaxial electrospray device; the hydrogel precursor is alginate; Step 2: freezing the monodisperse core-shell droplets prepared in step 1, and then cross-linking them with divalent metal ions to induce double gelation of the core layer and the shell layer to obtain hydrogel microspheres with a core-shell structure; the divalent metal ions are barium ions; Step 3: freeze-dry the core-shell hydrogel microspheres obtained in step 2 to obtain high-load MXene-encapsulated magnetic porous microcapsules.

2. The use of the high-load MXene-encapsulated magnetic porous microcapsules for adsorption according to claim 1 in the preparation of a product for adsorbing uremic toxins, characterized in that: in, The specific method of step 2 is: collecting the monodisperse core-shell droplets prepared in step 1 in a container filled with liquid nitrogen, and immediately pouring a divalent metal ion solution into the container after the liquid nitrogen evaporates, thereby inducing double gelation of the core layer and the shell layer to obtain hydrogel microspheres with a core-shell structure.

3. Use of the high-load MXene-encapsulated magnetic porous microcapsules for adsorption according to claim 1 in the preparation of a product for adsorbing uremic toxins, characterized in that: in, In step 2, the cross-linking time is 20 to 40 minutes.

4. The use of the high-load MXene-encapsulated magnetic porous microcapsules for adsorption according to claim 1 in the preparation of a product for adsorbing uremic toxins, characterized in that: in, In step 1, in the hydrogel precursor solution doped with magnetic nanoparticles, the concentration of the magnetic nanoparticles relative to the hydrogel precursor solution is 0.5-2 wt %, the concentration of the hydrogel precursor solution is 1.5-3 wt %; and the concentration of the MXene dispersion is 30-45 mg / ml.

5. The use of the high-load MXene-encapsulated magnetic porous microcapsules for adsorption according to claim 2 in the preparation of a product for adsorbing uremic toxins, characterized in that: in, In step 2, the concentration of the divalent metal ion solution is 0.5-2 wt%.

6. Use of the high-load MXene-encapsulated magnetic porous microcapsules for adsorption according to claim 2 in the preparation of a product for adsorbing uremic toxins, characterized in that: in, In step 2, the container is a container made of polytetrafluoroethylene.

7. Use of the high-load MXene-encapsulated magnetic porous microcapsules for adsorption according to claim 1 in the preparation of a product for adsorbing uremic toxins, characterized in that: in, In step 1, the inner phase flow rate is 0.5-4 ml / h, the outer phase flow rate is 1-6 ml / h, the receiving distance is 4-10 cm, and the voltage is +4-+10 kV.

Images