A soluble microneedle patch loaded with fe s2 nanoparticles and preparation and application thereof

Abstract

The application discloses a soluble microneedle patch loaded with FeS2 nanoparticles and a preparation and application thereof. The preparation method comprises the following steps: using polyvinylpyrrolidone as a surface stabilizer, and preparing FeS2 nanoparticles by using an ethylene glycol solvothermal method; mixing the nanoparticles with a needle body matrix solution to prepare a needle body casting solution; and then filling a microneedle mold, vacuumizing, back layer compounding, drying and demolding to obtain the FeS2@MN microneedle patch. The obtained microneedle patch has a complete appearance, good mechanical strength, skin puncture capacity and rapid dissolution and release performance, can realize stable temperature rise under 808 nm near-infrared irradiation, and exhibits good in-vitro antibacterial and antibiofilm effects on methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Meanwhile, the microneedle patch can promote endothelial cell migration and tube formation, and is suitable for local treatment of bacterial infection wounds.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials and transdermal delivery technology, specifically to a soluble microneedle patch loaded with FeS2 nanoparticles and its preparation and application. Background Technology

[0002] Chronic infected wounds often present problems during the repair process, including persistent bacterial colonization, biofilm formation, prolonged local inflammation, and insufficient angiogenesis. Simultaneously, the wound surface is frequently covered with exudate, necrotic tissue, and biofilm-like substances, making it difficult for topical medications to fully reach the lesion and penetrate deeper tissues. Consequently, the treatment cycle is prolonged and recurrence is common.

[0003] Currently, local treatments for infected wounds mainly include antibiotic ointments, irrigation solutions, wet dressings, and topical application after debridement. These methods are effective in reducing the number of bacteria on the surface, but when faced with drug-resistant strains that form biofilms, they often suffer from insufficient depth of action, limited local retention time, and poor treatment persistence; frequent dressing changes also increase the burden on patients.

[0004] Microneedle patches are a type of minimally invasive local delivery platform capable of penetrating the wound surface barrier to deliver active ingredients to local tissues or micropore channels with minimal bleeding. They have a promising foundation for applications in local anti-infection and wound management. Hyaluronic acid possesses excellent biocompatibility, biodegradability, and moisturizing properties. Using it to prepare soluble microneedles facilitates both microneedle formation and rapid dissolution of the patch after insertion, thereby achieving local release.

[0005] On the other hand, inorganic nanomaterials with photothermal response and enzyme-like activity have attracted attention for their role in bacterial clearance and wound microenvironment regulation. Combining such functional nanoparticles with soluble microneedles is expected to simultaneously improve local delivery efficiency, enhance antibacterial effects, and maintain the material functionality required for wound treatment.

[0006] FeS2 nanoparticles exhibit good near-infrared response and local antibacterial potential, producing a temperature rise suitable for local treatment under near-infrared irradiation. However, if FeS2 nanoparticles are directly dripped or coated onto the wound surface, the material is easily diluted by exudate or lost during dressing changes, making stable and precise local delivery difficult and limiting material utilization.

[0007] Therefore, it is necessary to provide a FeS2 microneedle patch with a clear preparation process, stable molding, rapid local delivery through microneedle array, and external antibacterial, anti-biofilm, and certain repair potential to meet the application needs of local treatment of infected wounds. Summary of the Invention

[0008] The primary objective of this invention is to overcome the shortcomings of the prior art and provide a soluble microneedle patch loaded with FeS2 nanoparticles. This patch loads FeS2 nanoparticles into a soluble microneedle array and can be used for infection-related local treatment. Under near-infrared irradiation conditions, the material exhibits good in vitro antibacterial, anti-biofilm, and endothelial cell migration and tubing effects.

[0009] A second objective of this invention is to provide a method for preparing the above-mentioned soluble microneedle patch.

[0010] A third objective of this invention is to provide applications of the aforementioned soluble microneedle patches.

[0011] To achieve the above objectives, the present invention adopts the following technical solution:

[0012] A method for preparing a soluble microneedle patch loaded with FeS2 nanoparticles includes the following steps:

[0013] (1) Polyvinylpyrrolidone was dissolved in a solvent, and ferric chloride, sodium acetate and sulfur powder were added under stirring. After ultrasonic dispersion, the mixture was heated to react. After the reaction was completed, FeS2 nanoparticles were obtained by centrifugation, washing and drying.

[0014] (2) Add FeS2 nanoparticles to the needle matrix solution and mix evenly to obtain needle casting liquid;

[0015] (3) Add the needle body molding liquid into the microneedle mold, and fill the needle cavity with the molding liquid by vacuuming, and remove the excess molding liquid from the surface of the mold;

[0016] (4) Add the backing material solution, dry and demold to obtain a soluble microneedle patch loaded with FeS2 nanoparticles.

[0017] Furthermore, the solvent mentioned in step (1) includes ethylene glycol.

[0018] Furthermore, the FeS2 nanoparticles obtained in step (1) can be pyrite phase nanoparticles with an average particle size of 3 to 10 nm. After the particles are dispersed in the hyaluronic acid needle matrix, they are mainly enriched in the microneedle array layer, which is beneficial to improving the delivery efficiency of the active components at the insertion site.

[0019] Furthermore, the needle matrix solution mentioned in step (2) is a hyaluronic acid solution; even further, the mass fraction of the hyaluronic acid solution is 8 wt.% to 12 wt.%.

[0020] Furthermore, the concentration of FeS2 nanoparticles in the needle casting solution in step (2) is 0.5–5.0 mg / mL.

[0021] Furthermore, the microneedle mold described in step (3) is a 15×15 array, with a single needle height of 550 μm, a needle base diameter of 210 μm, and a needle spacing of 600 μm.

[0022] Furthermore, the mechanical compressive strength of each needle of the microneedle patch obtained in step (4) is 0.4 to 1.0 N; after the patch is inserted into the skin, the needle tip can undergo significant dissolution and release FeS2 nanoparticles within 5 minutes.

[0023] Furthermore, the backing material solution mentioned in step (4) is a hyaluronic acid solution; even further, the mass fraction of the hyaluronic acid solution is 8 wt.% to 12 wt.%.

[0024] A soluble microneedle patch loaded with FeS2 nanoparticles was prepared by the above-described method.

[0025] The above-mentioned soluble microneedle patch loaded with FeS2 nanoparticles is used in the preparation of antibacterial products.

[0026] Furthermore, the bacteria include one of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa.

[0027] Furthermore, the antibacterial product is an antibacterial product suitable for photothermal therapy; even further, the photothermal therapy irradiation conditions are: power density of 0.75–1.25 W / cm², irradiation time of 2–5 min; even further, the irradiation is near-infrared light irradiation.

[0028] The above-mentioned soluble microneedle patch loaded with FeS2 nanoparticles is used in the preparation of products that promote wound healing.

[0029] Furthermore, the application is in the preparation of products that promote the repair of bacterial infection wounds.

[0030] Furthermore, the bacteria include one of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa.

[0031] Furthermore, the product for promoting wound healing is a product suitable for photothermal therapy; even further, the photothermal therapy light conditions are: power density of 0.75-1.25 W / cm², irradiation time of 2-5 min; even further, the light irradiation is near-infrared light irradiation.

[0032] Compared with the prior art, the present invention has the following beneficial effects:

[0033] (1) The present invention uses a material system combining FeS2 nanoparticles and hyaluronic acid soluble microneedles. The composition is relatively simple, the main process route is clear, and it is easy to repeat the preparation and scale up the subsequent process.

[0034] (2) The microneedle patch prepared by the present invention has a complete morphology and good mechanical properties. It can effectively puncture the skin and dissolve quickly after insertion, thereby establishing a local delivery channel and releasing FeS2 nanoparticles.

[0035] (3) The microneedle patch of the present invention has a good inhibitory effect on MRSA and Pseudomonas aeruginosa in vitro, and can reduce the corresponding biofilm residue, making it suitable for infection-related local antibacterial treatment.

[0036] (4) The microneedle patch of the present invention has a stable photothermal response under near-infrared irradiation, and the local temperature rise is within the temperature range suitable for local treatment of wounds.

[0037] (5) The microneedle patch of the present invention can promote endothelial cell migration and tube formation, indicating that the material system has certain repair potential in addition to antibacterial properties.

[0038] (6) The present invention adopts the technical route of “nanoparticle preparation - needle casting liquid construction - microneedle molding - in vitro functional evaluation”. The supporting relationship in the specification is clear, which facilitates subsequent patent implementation and technology transfer. Attached Figure Description

[0039] Figure 1 Here are (a) a transmission electron microscope image and (b) a particle size distribution diagram of FeS2 nanoparticles in this embodiment of the invention;

[0040] Figure 2 The following are the XPS total spectrum, (b) high-resolution XPS spectrum of Fe 2p and (c) high-resolution XPS spectrum of S 2p nanoparticles in the embodiments of the present invention;

[0041] Figure 3 Here are (a) scanning electron microscope images and (b) elemental distribution diagrams of the FeS2@MN microneedle patch in this embodiment of the invention;

[0042] Figure 4 This is an H&E staining image of the FeS2@MN microneedle patch after skin insertion in an embodiment of the present invention;

[0043] Figure 5 The images show (a) photothermal curve and (b) infrared thermal image of the FeS2@MN microneedle patch in this embodiment of the invention.

[0044] Figure 6 The above figures show the in vitro antibacterial results of FeS2@MN microneedle patches against (a) MRSA and (b) Pseudomonas aeruginosa in this embodiment of the invention.

[0045] Figure 7 The images show the results of FeS2@MN microneedle patch disruption of (a) MRSA and (b) Pseudomonas aeruginosa biofilms in this embodiment of the invention.

[0046] Figure 8 This is a diagram showing the results of FeS2@MN microneedle patch promoting endothelial cell migration in an embodiment of the present invention;

[0047] Figure 9 This is a diagram showing the results of FeS2@MN microneedle patch promoting endothelial cell tube formation in an embodiment of the present invention.

[0048] Figure 10 The images show the fluorescence imaging results of intracellular ROS levels of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa after treatment in each group in Example 6; where a is the result image of MRSA and b is the result image of Pseudomonas aeruginosa.

[0049] Figure 11 The graphs show the relative expression levels of HSP70 in each group after treatment in Example 7; where a is the result for methicillin-resistant Staphylococcus aureus and b is the result for Pseudomonas aeruginosa.

[0050] Figure 12 This is a graph showing the expression levels of genes related to the positive regulation of angiogenesis after treatment in each group in Example 8.

[0051] Figure 13 The images show the wound healing results after treatment in each group in Example 9; where a is a wound image and b is a quantitative analysis of the wound area. Detailed Implementation

[0052] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited to the following embodiments. Unless otherwise specified, the reagents, methods and equipment used in the embodiments are all conventional reagents, methods and equipment in the art. The embodiments in this specification mainly involve the preparation of FeS2 nanoparticles, the molding and characterization of FeS2@MN microneedle patches, in vitro antibacterial and anti-biofilm evaluation, and endothelial cell migration and tube formation related experiments.

[0053] Example 1

[0054] In this embodiment, a soluble microneedle patch loaded with FeS2 nanoparticles was prepared according to the following steps:

[0055] (1) Preparation of FeS2 nanoparticles: 0.7 g of polyvinylpyrrolidone was weighed and dispersed in 30 mL of ethylene glycol. 0.25 g of ferric chloride hexahydrate was added under magnetic stirring and stirring was continued to ensure that the iron salt was fully dispersed. Then, 3.6 g of sodium acetate was added and stirred evenly. 0.2 g of sulfur powder was added and ultrasonically dispersed for 1 h. The resulting mixture was transferred to a 40 mL polytetrafluoroethylene-lined reactor and reacted at 473 K for 12 h. After the reaction was completed, the mixture was naturally cooled to room temperature. The black product was collected by centrifugation and washed successively with chloroform, anhydrous ethanol and ultrapure water to remove unreacted raw materials, free sulfur and surface impurities. FeS2 nanoparticles were obtained after vacuum freeze-drying.

[0056] (2) Preparation of needle molding solution: A 10 wt.% hyaluronic acid solution was prepared, and after it was completely dissolved, 3 mg of FeS2 nanoparticles were added. The mixture was then ultrasonically dispersed to form a uniform mixture, thus obtaining the needle molding solution. In this embodiment, hyaluronic acid was used as both the microneedle matrix material and the backing film material to ensure good integrity between the microneedle array and the backing layer.

[0057] (3) Preparation of microneedle patch: The needle casting liquid obtained in step (2) was added to a PDMS microneedle mold. The mold was a 15×15 array with a single needle height of about 550 μm, a needle base diameter of about 210 μm, and a needle spacing of about 600 μm. Vacuum was applied for 5 min at −0.08 MPa and then restored to normal pressure. This process was repeated 3 times to ensure that the needle cavity was fully filled. After scraping off the excess liquid from the mold surface, 10 wt.% hyaluronic acid solution was added as a backing layer. The mold was then dried overnight at a constant temperature. After demolding, FeS2@MN microneedle patch was obtained. The obtained patch consists of a backing layer and a microneedle array layer, in which FeS2 nanoparticles are mainly distributed in the microneedle array layer.

[0058] (4) Preparation of blank control microneedles: Except for the absence of FeS2 nanoparticles in step (2), the other steps are the same to prepare HA@MN. This blank microneedle can be used as a control group for subsequent evaluation of microneedle morphology, skin insertion and in vitro function.

[0059] Example 2

[0060] The FeS2 nanoparticles prepared in Example 1 were characterized, and the results are as follows: Figure 1 and Figure 2 As shown. Transmission electron microscopy results show that the obtained FeS2 nanoparticles are uniformly dispersed in a near-spherical shape with a relatively concentrated particle size distribution and an average particle size of about 5.6 nm. High-resolution transmission electron microscopy can observe a crystal plane spacing of about 0.22 nm, corresponding to the (211) crystal plane of pyrite phase FeS2, indicating that the obtained product has good crystallinity.

[0061] like Figure 2As shown, X-ray photoelectron spectroscopy results indicate characteristic peaks near 707.2 eV and 719.8 eV in the Fe 2p high-resolution spectrum, and characteristic peaks near 162.4 eV and 163.6 eV in the S 2p high-resolution spectrum. Combined with transmission electron microscopy results, this further confirms that the obtained product is FeS2 nanoparticles. The above characterization results demonstrate that the solvothermal method used in this embodiment can stably obtain FeS2 nanoparticles suitable for microneedle loading.

[0062] In this embodiment, the near-infrared photothermal performance of FeS2 nanoparticles was also evaluated. When the FeS2 concentration was 150 μg / mL and the irradiation power density was 1.0 W / cm², the temperature could rise to about 44 °C within 10 min, indicating that the particles possess the basic photothermal response capability required for application with microneedle patches.

[0063] Example 3

[0064] The FeS2@MN microneedle patch prepared in Example 1 was characterized, and the results are as follows: Figures 3 to 5 As shown in the figure. Scanning electron microscopy results show that the obtained microneedle patch has a regular arrangement of needles and intact needle tips. The actual height of a single needle is about 575 μm, the needle base diameter is about 220 μm, and the needle spacing is about 550 μm. The elemental distribution results show that Fe and S elements are mainly distributed in the needle body region, indicating that FeS2 nanoparticles have been successfully loaded into the microneedles and are mainly located in the needle body part.

[0065] Mechanical performance tests showed that each FeS2@MN microneedle patch could withstand a compressive force of approximately 0.6–0.8 N, meeting the mechanical strength requirements for skin puncture. Compared to blank microneedles, the microneedles loaded with FeS2 maintained good overall structural stability, indicating that the addition of FeS2 did not have a significant adverse effect on microneedle formation.

[0066] like Figure 4 As shown, after the FeS2@MN microneedle patch was pressed into detached pig skin, uniformly distributed micropores were observed on the skin surface; H&E staining results showed that the microneedle insertion depth was approximately 303 μm. After insertion into the skin, the needle tip dissolved significantly within 5 minutes; in vitro release experiments showed that the release rate of FeS2 nanoparticles was close to 100% within 5 minutes, indicating that the microneedle patch has a rapid local delivery capability.

[0067] like Figure 5As shown, the FeS2@MN microneedle patch can rapidly heat up under 808 nm near-infrared irradiation; when the irradiation power density is 1.0 W / cm², the surface temperature of the microneedles can stabilize at approximately 44.1 °C within 5 min. These results indicate that the FeS2@MN microneedle patch prepared in this embodiment possesses good formability, puncture resistance, rapid dissolution and release capability, and stable photothermal response performance.

[0068] Example 4

[0069] Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa were used as experimental strains to evaluate the in vitro antibacterial activity of the FeS2@MN microneedle patch prepared in Example 1. The results are as follows: Figure 6 As shown in the figure. The experiment included PBS, HA@MN, and FeS2@MN groups, and compared colony formation under near-infrared (NIR) irradiation conditions. The results showed that under NIR irradiation, the number of colonies in the FeS2@MN group was significantly reduced, and its in vitro antibacterial effect was significantly better than the blank group and the HA@MN group.

[0070] Further evaluation of the biofilm was performed using live / dead bacterial fluorescence staining, and the results were as follows: Figure 7 As shown, FeS2@MN significantly reduced the residual amount of MRSA and Pseudomonas aeruginosa biofilms under near-infrared irradiation, with a biofilm removal rate of approximately 75%. Simultaneously, the dead bacteria signal was significantly enhanced, indicating that this microneedle patch not only inhibits the growth of planktonic bacteria but also disrupts mature biofilms.

[0071] The above results indicate that the FeS2@MN microneedle patch of the present invention has good in vitro antibacterial and anti-biofilming capabilities, and can be used in local treatment scenarios related to bacterial infection.

[0072] Example 5

[0073] The angiogenesis-related properties of the FeS2@MN microneedle patch prepared in Example 1 were evaluated using human umbilical vein endothelial cells (HUVECs). The experiment included PBS, HA@MN, and FeS2@MN groups, with some groups receiving supplemental 808 nm near-infrared irradiation. Figure 8 As shown in the figure, the scratch test results show that FeS2@MN can significantly improve the migration speed of HUVECs under near-infrared irradiation conditions, and the scratch closure rate is close to 95% after 24 h.

[0074] like Figure 9As shown, Matrigel tube formation experiments revealed that FeS2@MN can form a denser and more continuous capillary-like network structure under near-infrared irradiation, exhibiting a higher number of branches and a more complete tube-like structure, indicating that it has a good pro-angiogenic ability.

[0075] The above results indicate that the FeS2@MN microneedle patch of the present invention can promote endothelial cell migration and tube formation, suggesting that in addition to in vitro antibacterial activity, this material system also has certain potential to promote repair.

[0076] In summary, this invention constructs a microneedle patch that combines rapid local delivery, in vitro antibacterial activity, anti-biofilm formation, and the ability to promote endothelial cell migration and tubulation by loading FeS2 nanoparticles into a hyaluronic acid-soluble microneedle array. This technical route is clear, the preparation process is controllable, and it is suitable as a local treatment material for infected wounds.

[0077] Example 6

[0078] DCFH-DA was used as a fluorescent probe to assess the production of glutathione (GSH)-induced intracellular reactive oxygen species (ROS) in bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa suspensions (10⁻¹⁰) were used. 7 ·CFU mL -1 The samples were co-incubated for 2 hours with PBS, GSH, HA@MN, FeS2@MN, FeS2@MN+GSH, PBS+NIR, GSH+NIR, HA@MN+NIR, FeS2@MN+NIR, or FeS2@MN+GSH+NIR, respectively. For the near-infrared light treatment group (+NIR group), the samples were incubated at 1.0 W cm⁻¹. − The bacteria were exposed to an 808 nm laser at an intensity of 5 min. After centrifugation to remove the supernatant, the bacteria were co-incubated in the dark with the reactive oxygen species (ROS) fluorescent dye DCFH-DA (10 μM) for 30 min, and then observed using a confocal laser scanning microscope (CLSM; excitation / emission wavelength = 485 / 525 nm).

[0079] The results are as follows Figure 10 As shown, FeS2@MN exhibits glutathione-responsive properties under near-infrared light, triggering cascade catalytic reactions and enhancing the generation of reactive oxygen species (ROS), suggesting a potential application in sterilization using reactive oxygen species.

[0080] Example 7

[0081] Commercially available ELISA kits were used to determine bacterial HSP70 expression levels according to the manufacturer's instructions. Bacteria were treated with PBS, mPTT, FeS2@MN+NIR, FeS2@MN+GSH, or FeS2@MN+GSH+NIR, respectively. In the mPTT group, PBS-treated bacteria were additionally incubated at 42 °C for 5 minutes. After treatment, bacterial cells were collected, washed with PBS, lysed, and centrifuged to obtain the supernatant. The HSP70 content in each sample was then determined by ELISA, and absorbance was recorded using a microplate reader. Relative HSP70 expression levels were calculated by normalizing the data to the control group.

[0082] The results are as follows Figure 11 As shown, FeS2@MN exhibits glutathione-responsive bactericidal properties at low temperatures (below 42 °C), which can circumvent the heat resistance of pathogens at relatively low temperatures and exert bactericidal effects by activating reactive oxygen species through glutathione activation.

[0083] Example 8

[0084] The transcriptional levels of angiogenesis-related genes in human umbilical vein endothelial cells (HUVECs) were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). HUVECs were divided into six groups: PBS, HA@MN, FeS2@MN, PBS(+), HA@MN(+), and FeS2@MN(+). After incubation under specified conditions for 24 hours, the groups marked "+" received irradiation with an 808 nm near-infrared (NIR) laser (power 1.0 W cm⁻¹). -2 The first group was cultured for 5 minutes, while the second group was cultured under the same conditions but without laser irradiation. Total RNA was extracted using PrimeScript RT reagent (TAKARA) and reverse transcribed into complementary DNA (cDNA). qRT-PCR was performed using a QuantStudio 6 Flex system (Life Technologies). GAPDH was used as an internal control gene. The relative expression levels of four representative angiogenesis-related genes were calculated.

[0085] The results are as follows Figure 12 As shown, FeS2@MN under NIR conditions can promote the expression of angiogenesis-related genes. FeS2@MN can promote the expression of repair-related genes in infected hosts while killing bacteria, thus promoting the repair of infected hosts.

[0086] Example 9

[0087] Male Sprague-Dawley (SD) rats (4–6 weeks old, 180–220 g) were purchased from Guangzhou Saiyoutai Biotechnology Co., Ltd. All animal experiments were conducted in accordance with the guidelines approved by the Animal Experiment Ethics Committee of Guangzhou Saiyoutai Biotechnology Co., Ltd. (IACUC No.: SYT2025066). Preoperatively, rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital (1.0 mL / kg). A full-thickness circular wound (10 mm in diameter) was created on the dorsal skin. Subsequently, each wound was inoculated with a suspension of methicillin-resistant Staphylococcus aureus (MRSA) (1×10⁻⁶ g / kg). 8 CFU mL -1 Animals were cultured for 48 hours to establish an infected wound model. They were then randomly divided into eight groups: control group (G1), vancomycin group (G2), HA@MN group (G3), HA@MN+NIR group (G4), FeS2 group (G5), FeS2+NIR group (G6), FeS2@MN group (G7), and FeS2@MN+NIR group (G8). During treatment, HA@MN or FeS2@MN dressings were applied directly to the wound site, while FeS2 dispersion was administered topically in the respective groups. For the near-infrared therapy group, an 808 nm laser at 1.0 W cm⁻¹ was used. -2 The wound was irradiated with a specific power. Infrared thermography was continuously recorded during irradiation, and corresponding temperature-time curves were obtained. Twelve days after treatment, wound tissue was collected, fixed in 4% paraformaldehyde, embedded in paraffin, and sectioned for histological and immunological analysis. Tissue regeneration and collagen deposition were assessed using hematoxylin and eosin (H&E) staining and Massen's trichrome staining. Angiogenesis was assessed using dual immunofluorescence staining for CD31 and α-SMA, and immunofluorescence staining for HIF-1α and VEGF. Furthermore, immunofluorescence staining for heat shock protein 90 (HSP90) was performed to assess the heat shock response in wound tissue after near-infrared irradiation. Inflammatory response was assessed using immunohistochemical staining for IL-10 and TNF-α. Major organs, including the heart, liver, spleen, lungs, and kidneys, were collected for H&E staining to further evaluate the in vivo biocompatibility of the nanozyme.

[0088] The results are as follows Figure 13 As shown, under both NIR and non-NIR conditions, FeS2@MN is superior to HA microneedles and FeS2 in promoting wound healing.

[0089] Those skilled in the art will understand that the above embodiments are for illustrative purposes only and do not constitute a limitation on the scope of protection of the present invention. Equivalent substitutions, conventional adjustments, or improvements made within the spirit and principles of the present invention should all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a soluble microneedle patch loaded with FeS2 nanoparticles, characterized in that, Includes the following steps: (1) Polyvinylpyrrolidone was dissolved in a solvent, and ferric chloride, sodium acetate and sulfur powder were added under stirring. After ultrasonic dispersion, the mixture was heated to react. After the reaction was completed, FeS2 nanoparticles were obtained by centrifugation, washing and drying. (2) Add FeS2 nanoparticles to the needle matrix solution and mix evenly to obtain needle casting liquid; (3) Add the needle body molding liquid into the microneedle mold, and fill the needle cavity with the molding liquid by vacuuming, and remove the excess molding liquid from the surface of the mold; (4) Add the backing material solution, dry and demold to obtain a soluble microneedle patch loaded with FeS2 nanoparticles.

2. The preparation method according to claim 1, characterized in that, The solvent mentioned in step (1) includes ethylene glycol.

3. The preparation method according to claim 1, characterized in that, The needle matrix solution mentioned in step (2) is a hyaluronic acid solution; The concentration of FeS2 nanoparticles in the needle casting solution in step (2) is 0.5–5.0 mg / mL.

4. The preparation method according to claim 3, characterized in that, The mass fraction of the hyaluronic acid solution mentioned in step (2) is 8 wt.% to 12 wt.%.

5. The preparation method according to claim 1, characterized in that, The microneedle mold described in step (3) is a 15×15 array with a single needle height of 550 μm, a needle base diameter of 210 μm, and a needle spacing of 600 μm.

6. The preparation method according to claim 1, characterized in that, The mechanical compressive strength of each needle in the microneedle patch obtained in step (4) is 0.4 to 1.0 N; The backing material solution mentioned in step (4) is a hyaluronic acid solution.

7. A soluble microneedle patch loaded with FeS2 nanoparticles, characterized in that, It is prepared by the preparation method according to any one of claims 1-6.

8. Application, characterized in that: The application is any one of the following A1) to A3): A1) The application of the soluble microneedle patch loaded with FeS2 nanoparticles as described in claim 7 in the preparation of antibacterial products; A2) The application of the soluble microneedle patch loaded with FeS2 nanoparticles as described in claim 7 in the preparation of products that promote wound repair; A3) The application of the soluble microneedle patch loaded with FeS2 nanoparticles as described in claim 7 in the preparation of products that promote the repair of bacterial infection wounds.

9. The application according to claim 8, characterized in that, The bacteria mentioned include one of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa; The antibacterial product mentioned is an antibacterial product suitable for photothermal therapy; The product mentioned above is a wound-healing product suitable for photothermal therapy; The product described above that promotes the repair of bacterial infection wounds is suitable for photothermal therapy.

10. The application according to claim 9, characterized in that, The photothermal therapy conditions are as follows: power density of 0.75–1.25 W / cm² and irradiation time of 2–5 min. The illumination mentioned is near-infrared light illumination.

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