Soluble antibacterial microneedle loaded with photosensitizer and preparation method of soluble antibacterial microneedle

Abstract

The invention provides a soluble antibacterial microneedle loaded with a photosensitizer and a preparation method of the soluble antibacterial microneedle, and belongs to the field of biomedical materials. The microneedle is composed of a substrate and a soluble polymer needle tip located on the substrate, a photosensitizer is loaded in the needle tip, and the substrate and the needle tip are of an integrally-formed structure; the photosensitizer is 5, 5-difluoro-2, 8-diiodo-1, 3, 7, 9-tetramethyl-10-phenyl-5H-dipyrrolo [1, 2-C: 2 ', 1'-F] [1, 3, 2] diazaborane-4-onium-5-urea, and the photosensitizer is 5, 5-difluoro-2, 8-diiodo-1, 3, 7, 9-tetramethyl-10-phenyl-5H-dipyrrolo [1, 2-C: 2 ', 1'-F] [1, 3, 2] The soluble polymer is polyvinylpyrrolidone. Compared with the prior art, the photosensitizer I-BDP excited by the green light is used, and due to the fact that the penetration depth of the green light is small, surrounding normal tissue is relatively less affected, and therefore the photosensitizer I-BDP has good tissue protectiveness when surface skin infection is treated.

Description

Technical Field

[0001] The invention belongs to the field of biomedical materials, and specifically relates to a soluble antibacterial microneedle loaded with a photosensitizer and a preparation method thereof. Background Art

[0002] Microneedles have emerged as a minimally invasive and effective transdermal drug delivery platform for rapid or sustained release. Compared with traditional transdermal patches, microneedles can penetrate the stratum corneum and provide a conduit through the epidermis, allowing for efficient and convenient delivery of various therapies into the skin. Soluble microneedles are made of soluble or degradable polymer materials. During drug delivery, the drug is released after the polymer material inside the soluble microneedle dissolves or degrades. This microneedle preparation method is simple, gentle, safe, and has a high drug loading rate, so it is considered a very promising delivery method.

[0003] Staphylococcus aureus (S. aureus) is an important zoonotic pathogen, and traditional antibiotic treatment is limited by drug resistance and side effects. Photodynamic antimicrobial therapy (PDAT) uses photosensitizers to produce reactive oxygen radicals (ROS) under excitation light irradiation to effectively kill bacteria, making it one of the promising methods for treating bacterial infections. However, due to the poor water solubility of common photosensitizers, they are prone to aggregation in physiological environments, which leads to a weakened PDAT effect. The hydrophilicity and amphiphilic ion properties of photosensitizers lead to poor permeability in the skin, and their low solubility further limits their bioavailability during transdermal administration. This may result in the inability of the drug to be effectively absorbed and exert its effect, thereby affecting the penetration of the drug and reducing its efficacy.

[0004] Although most existing technologies use water-soluble photosensitizers loaded in microneedles to improve skin permeability, common photosensitizers often have problems with poor solubility and insufficient stability in practical applications. Therefore, it is usually necessary to use highly toxic organic solvents to dissolve water-insoluble photosensitizers, and some organic solvents cannot be completely removed, which not only increases safety risks, but also limits the clinical adaptability of microneedles.

[0005] In addition, the preparation of microneedles currently faces many challenges. The height, diameter and spacing of microneedles require very precise results, and traditional preparation methods (such as molding, etching, etc.) may find it difficult to meet the requirements of high precision and high repeatability.

[0006] As an emerging technology, surface projection micro-stereolithography has become an ideal choice for manufacturing high-precision microneedles due to its advantages of customization, rapid manufacturing, low-cost large molding area and high processing accuracy. Combining microneedle preparation with micro-stereolithography can significantly improve the efficiency and quality of microneedle manufacturing by utilizing its high resolution, flexible design capabilities and multi-material processes, thereby promoting the application of microneedle technology in biomedicine and drug delivery.

[0007] Therefore, this invention has significant significance in improving the efficacy, safety and microneedle manufacturing of photodynamic antibacterial therapy. Summary of the invention

[0008] The purpose of the present invention is to solve the problem of weakened antibacterial effect and poor skin permeability caused by poor water solubility of existing water-insoluble photosensitizers, and to provide a soluble antibacterial microneedle loaded with a photosensitizer and a preparation method thereof.

[0009] The present invention provides a soluble antibacterial microneedle loaded with a photosensitizer, the microneedle is composed of a substrate and a soluble polymer needle tip located on the substrate, the needle tip is loaded with a photosensitizer, and the substrate and the needle tip are an integrally formed structure;

[0010] The photosensitizer is 5,5-difluoro-2,8-diiodo-1,3,7,9-tetramethyl-10-phenyl-5H-dipyrrolo[1,2-C:2',1'-F][1,3,2]diazaborol-4-ium-5-urea I-BDP;

[0011] The soluble polymer is polyvinyl pyrrolidone.

[0012] The present invention provides a method for preparing a soluble antibacterial microneedle loaded with a photosensitizer, comprising the following steps:

[0013] Step 1: Prepare HTL resin microneedle positive mold using surface projection microstereolithography;

[0014] Step 2: preparing a polydimethylsiloxane (PDMS) microneedle negative mold;

[0015] Step 3: evenly dispersing I-BDP in an anhydrous ethanol solution, adding polyvinyl pyrrolidone into the solution to dissolve it, thereby forming a solution containing I-BDP and polyvinyl pyrrolidone;

[0016] Step 4: Drop the solution containing I-BDP and polyvinyl pyrrolidone obtained in step 3 onto the surface of the polydimethylsiloxane (PDMS) microneedle negative mold, allow the drug to enter the tip of the mold in a vacuum environment, and recover excess solution; add the polyvinyl pyrrolidone solution to the polydimethylsiloxane (PDMS) mold loaded with photosensitizer I-BDP and polyvinyl pyrrolidone, and fill the mold with the soluble polymer solution under vacuum; let it stand and dry, then peel off the polydimethylsiloxane (PDMS) microneedle negative mold to obtain microneedles.

[0017] Preferably, in the step 1, a positive HTL resin microneedle mold is prepared using surface projection microstereolithography, with a z-axis resolution of 5 μm, a needle tip designed to be conical, and the needle tips are placed with a center-to-center spacing of 600 μm and arranged in a 10×10 array. The microneedles contain 100 needle tips in total, with a needle height of 100-2000 μm, a needle base width of 50-600 μm, and a needle center spacing of 100-2000 μm. The resulting mold is immersed in isopropanol overnight and dried in an oven at 80-100°C for 8-20 hours. After that, ultraviolet light is projected onto each surface of the two molds for at least 2 hours.

[0018] Preferably, the preparation of the polydimethylsiloxane (PDMS) microneedle negative mold described in step 2 is specifically as follows:

[0019] Place polydimethylsiloxane (PDMS) and curing agent in a beaker, stir for 5-8 minutes, then put it in a vacuum tank to remove bubbles to obtain a mixture, stick the printed HTL resin microneedle positive mold on the bottom of the culture dish, and then pour the above mixture into the culture dish to make it 3-4 mm thick; put the culture dish into a vacuum tank to remove all bubbles in the mixture, heat it at 80-100°C for 1-2 hours to solidify the polydimethylsiloxane (PDMS); after cooling, peel off the solidified polydimethylsiloxane (PDMS) and the HTL resin microneedle positive mold to obtain a polydimethylsiloxane (PDMS) microneedle negative mold.

[0020] Preferably, the mass ratio of polydimethylsiloxane (PDMS) to curing agent is 10:1.

[0021] Preferably, in the solution of I-BDP and polyvinyl pyrrolidone in step 3, the concentration of I-BDP is 0.5-2 mg / mL, the concentration of polyvinyl pyrrolidone is 100-200 mg / mL, and the number average molecular weight of polyvinyl pyrrolidone is 130 kDa.

[0022] Beneficial Effects of the Invention

[0023] The present invention provides a soluble antibacterial microneedle loaded with a photosensitizer and a preparation method thereof. The present invention uses a photosensitizer I-BDP excited by green light. Since the penetration depth of green light is relatively shallow, it relatively rarely affects the surrounding normal tissues, so it has good tissue protection when treating superficial skin infections. By selecting an anhydrous ethanol solution with relatively low toxicity as a solvent to dissolve the photosensitizer, replacing traditional dichloromethane or dimethyl sulfoxide, and using polyvinylpyrrolidone that can be well dissolved in anhydrous ethanol solution, the loading capacity of the photosensitizer is effectively enhanced, and its stability and biocompatibility are improved, thereby solving the problem of weakened antibacterial effect and poor skin permeability caused by poor water solubility of the photosensitizer in photodynamic therapy.

[0024] In addition, the present invention utilizes surface projection micro-stereolithography technology, which combines high resolution with flexible design capabilities, significantly improves the efficiency and quality of microneedle manufacturing, and ensures the superior performance of the prepared microneedles in structure and function. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Microscope images and scanning electron microscope images of the soluble antibacterial microneedles loaded with I-BDP prepared in Example 1 of the present invention;

[0026] Figure 2 This is a diagram showing the transdermal effect of the soluble antibacterial microneedle loaded with I-BDP prepared in Example 1 of the present invention;

[0027] Figure 3 This is a curve diagram of the generation of singlet oxygen in vitro under laser irradiation of the soluble antibacterial microneedles loaded with I-BDP prepared in Example 1 of the present invention;

[0028] Figure 4 This is a graph showing the effect of the in vitro anti-Staphylococcus aureus biofilm activity of the soluble I-BDP-loaded polyvinyl pyrrolidone microneedles prepared in Example 1 of the present invention at a wavelength of 532 nm;

[0029] Figure 5 The schematic diagram of the preparation process of the soluble antibacterial microneedle loaded with photosensitizer of the present invention includes: 1. a negative mold of a polydimethylsiloxane (PDMS) microneedle; 2. a mixed solution containing a photosensitizer and polyvinyl pyrrolidone; 3. a polyvinyl pyrrolidone solution; and 4. a microneedle. DETAILED DESCRIPTION

[0030] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0031] The present invention first provides a soluble antibacterial microneedle loaded with a photosensitizer. The microneedle consists of a substrate and a soluble polymer needle tip located on the substrate. The needle tip carries the photosensitizer, and the substrate and the needle tip are an integrally formed structure. The photosensitizer is 5,5-difluoro-2,8-diiodo-1,3,7,9-tetramethyl-10-phenyl-5H-dipyrrolo[1,2-C:2',1'-F][1,3,2]diazaborolane-4-ium-5-urea I-BDP; and the soluble polymer is polyvinylpyrrolidone.

[0032] The present invention also provides a method for preparing a soluble antibacterial microneedle loaded with a photosensitizer, such as Figure 5As shown, the following steps are included:

[0033] Step 1: Prepare HTL resin microneedle positive mold using surface projection microstereolithography;

[0034] Step 2: preparing a polydimethylsiloxane (PDMS) microneedle negative mold;

[0035] Step 3: Dispersing I-BDP uniformly in an anhydrous ethanol solution, adding polyvinyl pyrrolidone to the solution to dissolve, and forming a solution of I-BDP and polyvinyl pyrrolidone; the concentration of I-BDP in the solution is preferably 0.5-2 mg / mL, the concentration of the polyvinyl pyrrolidone is preferably 100-200 mg / mL, and the number average molecular weight of the polyvinyl pyrrolidone is 130 kDa;

[0036] Step 4: Drop the solution containing I-BDP and polyvinyl pyrrolidone obtained in step 3 onto the surface of the polydimethylsiloxane (PDMS) microneedle negative mold, allow the drug to enter the tip of the mold in a vacuum environment, and recover excess solution; add the polyvinyl pyrrolidone solution to the polydimethylsiloxane (PDMS) mold loaded with photosensitizer I-BDP and polyvinyl pyrrolidone, and fill the mold with the soluble polymer solution under vacuum; let it stand and dry, then peel off the polydimethylsiloxane (PDMS) microneedle negative mold to obtain microneedles.

[0037] According to the present invention, the preparation of the HTL resin microneedle positive mold in step 1 preferably includes: using surface projection microstereolithography (BMF Nanomaterial Technology Co., Ltd.) to prepare the HTL resin microneedle positive mold, the z-axis resolution is 5μm, the needle tip is designed to be conical, the needle tip is placed with a center-to-center spacing of 600μm, and arranged in a 10×10 array, the microneedles contain 10×10, a total of 100 needle tips, a needle height of 100-2000μm, a needle base width of 50-600μm, and a needle center spacing of 100-2000μm. The obtained mold is immersed in isopropanol overnight and dried in an oven at 80-100°C for 8-20h, and then, ultraviolet light is projected onto each surface of the two molds for at least 2h.

[0038] According to the present invention, the preparation of the polydimethylsiloxane (PDMS) microneedle negative mold in the step 2 preferably includes: placing polydimethylsiloxane (PDMS) and a curing agent preferably in a beaker at a mass ratio of 10:1, stirring for 5-8 minutes, and then placing in a vacuum tank at 25°C, in a vacuum environment with a vacuum degree of -0.08MPa for 10-12 minutes, removing bubbles to obtain a mixture, and sticking the printed HTL resin microneedle positive mold to the bottom of a disposable culture dish, and then pouring the above mixture into the disposable culture dish to a thickness of 3-4mm; placing the culture dish in a vacuum tank, evacuating to a vacuum degree of -0.08MPa to remove bubbles in the mixture; heating at 80-100°C for 1-2h to solidify the polydimethylsiloxane (PDMS); after cooling, peeling off the solidified polydimethylsiloxane (PDMS) and the HTL resin microneedle positive mold to obtain a polydimethylsiloxane (PDMS) microneedle negative mold.

[0039] According to the present invention, 200 μL of the solution containing I-BDP and polyvinyl pyrrolidone obtained in step three is poured on the surface of the polydimethylsiloxane (PDMS) microneedle negative mold, and the drug is allowed to enter the tip of the mold in a vacuum environment of -0.08 MPa at 25°C, and the excess solution is recovered; 100 mg / mL of polyvinyl pyrrolidone solution is added to the polydimethylsiloxane (PDMS) mold loaded with I-BDP and polyvinyl pyrrolidone, and the polyvinyl pyrrolidone solution is filled in the mold under vacuum; after standing for 10 minutes, it is taken out and then dried at 25°C for 12 hours, and then the polydimethylsiloxane (PDMS) microneedle negative mold is peeled off to obtain microneedles loaded with I-BDP and polyvinyl pyrrolidone.

[0040] The steps of applying the soluble microneedle to photodynamic therapy of the present invention include: (1) inserting the soluble antibacterial microneedle loaded with photosensitizer into the affected area, pressing for a certain time until the tip of the microneedle dissolves and then removing it; (2) irradiating the needle-inserted area with excitation light of a specific wavelength after a certain time. The pressing time is preferably 1 second to 10 minutes, and the time interval from the start of pressing to the excitation light irradiation is 4 hours to 24 hours.

[0041] The present invention is further described in detail below with reference to specific examples, and the raw materials involved in the examples are all commercially available.

[0042] Example 1: Preparation of soluble antibacterial microneedles loaded with I-BDP

[0043] 1. Preparation of HTL resin microneedle positive mold: HTL resin microneedle positive mold was prepared using surface projection microstereolithography (BMF Nanomaterial Technology Co., Ltd.) with a z-axis resolution of 5 μm. The needle tip was designed to be conical. The needle tips were placed with a center-to-center spacing of 600 μm and arranged in a 10×10 array. The microneedles contained 100 needle tips in total, with a needle height of 100-2000 μm, a needle base width of 50-600 μm, and a needle center spacing of 100-2000 μm. The resulting mold was soaked in isopropanol overnight and dried in an oven at 80-100°C for 8-20 h. After that, UV light was projected onto each surface of the two molds for at least 2 h.

[0044] 2. Preparation of polydimethylsiloxane (PDMS) microneedle negative mold: polydimethylsiloxane (PDMS) and curing agent (Dow Corning 184) are placed in a beaker at a mass ratio of 10:1, stirred for about 5 minutes, and then placed in a vacuum tank at 25°C, in a vacuum environment of -0.08MPa for 10 minutes to remove bubbles, and the printed HTL resin microneedle positive mold is attached to the bottom of a disposable culture dish, and then the above mixture is poured into a disposable culture dish to a thickness of about 3-4mm; the culture dish is placed in a vacuum tank and evacuated to a vacuum degree of -0.08MPa to remove all bubbles in the mixture; the polydimethylsiloxane (PDMS) is cured by heating at 80°C for 2h; after cooling, the cured polydimethylsiloxane (PDMS) and the HTL resin microneedle positive mold are peeled off to obtain a polydimethylsiloxane (PDMS) microneedle negative mold.

[0045] 3. Dispersing I-BDP uniformly in an anhydrous ethanol solution, adding polyvinyl pyrrolidone to the solution to dissolve, thereby forming a solution of I-BDP and polyvinyl pyrrolidone, wherein the concentration of I-BDP in the solution is 1 mg / mL, the concentration of the polyvinyl pyrrolidone is 100 mg / mL, and the number average molecular weight of the polyvinyl pyrrolidone is 130 kDa;

[0046] 4. Pour 200 μL of the solution containing I-BDP and polyvinyl pyrrolidone obtained in step 3 on the surface of the female mold of polydimethylsiloxane (PDMS) microneedle, and allow the drug to enter the tip of the mold in a vacuum environment of -0.08 MPa at 25°C, and recover the excess solution; add 100 mg / mL of polyvinyl pyrrolidone solution to the female mold of polydimethylsiloxane (PDMS) loaded with I-BDP and polyvinyl pyrrolidone, and fill the female mold of polydimethylsiloxane (PDMS) with the polyvinyl pyrrolidone solution under vacuum; take it out after leaving it for 10 minutes, and then dry it at 25°C for 12 hours, and then peel off the female mold of polydimethylsiloxane (PDMS) microneedle to obtain microneedles loaded with I-BDP and polyvinyl pyrrolidone. Figure 1 As shown, Figure 1a is a microscope image of soluble antibacterial microneedles loaded with I-BDP; Figure 1 b is a scanning electron microscopy image of soluble antibacterial microneedles loaded with I-BDP.

[0047] Comparative Example 1

[0048] The polyvinyl pyrrolidone in Example 1 was replaced with hyaluronic acid to form a solution containing I-BDP and hyaluronic acid. However, since hyaluronic acid is insoluble in ethanol, a solution cannot be formed, and soluble antibacterial microneedles loaded with I-BDP cannot be prepared.

[0049] Comparative Example 2

[0050] The anhydrous ethanol solution in Example 1 was replaced with a deionized water solution, and after I-BDP was uniformly dispersed in deionized water, polyvinyl pyrrolidone was added to form a solution containing I-BDP and polyvinyl pyrrolidone. Although polyvinyl pyrrolidone can be dissolved in deionized water, the photosensitizer is insoluble in water, causing it to precipitate in the mixed solution and unable to generate active oxygen through green light excitation to kill bacteria. Therefore, the prepared soluble antibacterial microneedles loaded with I-BDP do not have antibacterial function.

[0051] Example 2: Testing the transdermal ability of soluble antibacterial microneedles loaded with I-BDP

[0052] 1. Prepare soluble antibacterial microneedles loaded with I-BDP according to the method described in Example 1;

[0053] 2. Prepare a piece of fresh pig skin, remove excess subcutaneous fat tissue, wash it, place it on a glass slide, and wipe it dry;

[0054] 3. Insert the soluble microneedles loaded with I-BDP vertically into the pig skin and press for 5 minutes before removing them;

[0055] Under 532nm excitation light, a laser confocal microscope was used to scan from shallow to deep layer by layer at 20μm intervals. At a certain depth, a regularly arranged hole matrix appeared. The holes were surrounded by red hollow circles, which were formed by the diffusion of I-BDP to the surrounding tissue after the microneedle dissolved. As the tip of the microneedle loaded with I-BDP gradually shrank, the deeper the scanning went, the smaller the red circle formed, the darker the color, and finally shrank to a red dot until it disappeared. Figure 2 shown. Figure 2 This is a diagram showing the transdermal effect of the soluble antibacterial microneedle loaded with I-BDP prepared in Example 1 of the present invention. Figure 2 From left to right in the middle are laser confocal microscopy scans from shallow to deep. This experimental result suggests that the drug-loaded tip of the microneedle can penetrate the skin to a certain depth and dissolve, delivering the drug contained therein to the tissue.

[0056] Example 3: Detection of singlet oxygen produced by soluble antibacterial microneedles loaded with I-BDP after light treatment;

[0057] The soluble antibacterial microneedles loaded with I-BDP were prepared according to the method described in Example 1, and the singlet oxygen production was quantitatively analyzed using 9,10-anthracenediyl-bis(methylene)dicarboxylic acid (ABDA). 1 O2 capacity, ABDA and I-BDP@PVP microneedle mixed solution was illuminated by green LED (18 mW cm -2 ) was irradiated for 160 seconds. During the experiment, the absorbance of the mixed solution at 400nm was measured every 20 seconds using a UV spectrometer. The experiment was divided into ABDA (microneedles without photosensitizer) group and ABDA and I-BDP@PVP microneedle mixed solution group. A / A0 = absorbance of the mixture after illumination / absorbance of the initial mixture

[0058] The experimental results are as follows Figure 3 As shown, Figure 3 This is a curve diagram of the generation of singlet oxygen in vitro by the soluble antibacterial microneedles loaded with I-BDP prepared in Example 1 of the present invention under laser irradiation; it can be seen that with the extension of light irradiation time, the absorbance of the ABDA and I-BDP@PVP microneedle groups decreased significantly, indicating that I-BDP was generated by photodynamic 1 O2 gradually increased and oxidized ABDA; while the absorbance of ABDA (microneedle group without photosensitizer) remained basically unchanged, indicating that I-BDP@PVP microneedles can produce a large amount of 1 O2, laying the foundation for subsequent photodynamic antibacterial therapy.

[0059] Example 4: In vitro anti-biofilm activity assay of soluble antibacterial microneedles loaded with I-BDP;

[0060] Soluble antibacterial microneedles loaded with I-BDP were prepared according to the method described in Example 1, and the mixed solution of I-BDP and polyvinyl pyrrolidone in Example 1 was replaced with the polyvinyl pyrrolidone solution in Example 1 to prepare empty microneedles (PVP microneedles) without I-BDP. Crystal violet (CV) is a basic dye that can bind to DNA in the cell nucleus to produce nuclear staining. Therefore, the CV staining method was used to further analyze the ability of I-BDP@PVP microneedles with excellent antibacterial activity to inhibit the formation of S. aureus biofilm. First, I-BDP@PVP microneedles were dissolved in S. aureus solution (1×10 7The mixed solution was added to a 24-well plate and incubated in a 37°C incubator for 30 min. The experimental groups were divided into a control group (PBS mixed with bacterial solution), a control group + light, a PVP microneedle group, a PVP microneedle group + light, an I-BDP@PVP microneedle group, and an I-BDP@PVP microneedle + light. The light group was exposed to green LED (18 mW cm -2 ) for 10 min. After incubation in a 37°C incubator for 24 h, the suspension was discarded, methanol was fixed for 30 min, excess methanol was discarded and dried. The biofilm was stained with CV solution for 30 min and washed with PBS. Acetic acid was then added and the light absorption value of the solution at a wavelength of 570 nm was measured to calculate the biomass to quantify the biofilm.

[0061] The experimental results are as follows Figure 4 As shown in the figure, in the absence of light, the control group (PBS mixed with bacterial solution), PVP microneedle group and I-BDP@PVP microneedle group could not inhibit biofilm formation. When green light was irradiated, the I-BDP@PVP microneedle group was the lightest in color after CV staining because it inhibited the formation of biofilm ( Figure 4 a), and the biofilm biomass was the lowest ( Figure 4 b), indicating that I-BDP@PVP microneedles can effectively inhibit the formation of S. aureus biofilm. In contrast, the control group (PBS mixed with bacterial solution) and the PVP microneedle group could not inhibit the formation of biofilm.

[0062] It will be easily understood by those skilled in the art that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. A soluble antibacterial microneedle loaded with a photosensitizer, characterized in that: The microneedle is composed of a substrate and a soluble polymer needle tip located on the substrate, a photosensitizer is loaded in the needle tip, and the substrate and the needle tip are an integrally formed structure; The photosensitizer is 5,5-difluoro-2,8-diiodo-1,3,7,9-tetramethyl-10-phenyl-5H-dipyrrolo[1,2-C:2',1'-F][1,3,2]diazaborol-4-ium-5-urea I-BDP; The soluble polymer is polyvinyl pyrrolidone.

2. The method for preparing a photosensitizer-loaded soluble antibacterial microneedle according to claim 1, characterized in that: The following steps are involved: Step 1: Prepare HTL resin microneedle positive mold using surface projection microstereolithography; Step 2: preparing a polydimethylsiloxane microneedle negative mold; Step 3: evenly dispersing I-BDP in an anhydrous ethanol solution, adding polyvinyl pyrrolidone into the solution to dissolve it, thereby forming a solution containing I-BDP and polyvinyl pyrrolidone; Step 4: Drop the solution containing I-BDP and polyvinyl pyrrolidone obtained in step 3 onto the surface of the polydimethylsiloxane microneedle negative mold, allow the drug to enter the tip of the mold in a vacuum environment, and recover excess solution; add the polyvinyl pyrrolidone solution to the polydimethylsiloxane mold loaded with photosensitizer I-BDP and polyvinyl pyrrolidone, and fill the mold with the soluble polymer solution under vacuum; let it stand and dry, then peel off the polydimethylsiloxane microneedle negative mold to obtain microneedles.

3. The method for preparing a photosensitizer-loaded soluble antibacterial microneedle according to claim 2, characterized in that: In the step 1, a positive mold of HTL resin microneedles is prepared by surface projection microstereolithography, with a z-axis resolution of 5 μm, a needle tip designed to be conical, and the needle tips are placed with a center-to-center spacing of 600 μm and arranged in a 10×10 array. The microneedles contain 100 needle tips in total, with a needle height of 100-2000 μm, a needle base width of 50-600 μm, and a needle center spacing of 100-2000 μm. The obtained mold is immersed in isopropanol overnight and dried in an oven at 80-100°C for 8-20 hours. After that, ultraviolet light is projected onto each surface of the two molds for at least 2 hours.

4. The method for preparing a photosensitizer-loaded soluble antibacterial microneedle according to claim 2, characterized in that: The preparation of the polydimethylsiloxane microneedle negative mold described in step 2 is specifically as follows: Place polydimethylsiloxane and curing agent in a beaker, stir for 5-8 minutes, then put it in a vacuum tank to remove bubbles to obtain a mixture, stick the printed HTL resin microneedle positive mold on the bottom of the culture dish, and then pour the above mixture into the culture dish to make it 3-4 mm thick; put the culture dish into a vacuum tank to remove all bubbles in the mixture, heat at 80-100°C for 1-2 hours to cure the polydimethylsiloxane; after cooling, peel off the cured polydimethylsiloxane (PDMS) and the HTL resin microneedle positive mold to obtain the polydimethylsiloxane microneedle negative mold.

5. The method for preparing a photosensitizer-loaded soluble antibacterial microneedle according to claim 2, characterized in that: The mass ratio of the polydimethylsiloxane to the curing agent is 10:

1.

6. The method for preparing a photosensitizer-loaded soluble antibacterial microneedle according to claim 2, characterized in that: In the step 3, the concentration of I-BDP in the solution of I-BDP and polyvinyl pyrrolidone is 0.5-2 mg / mL, the concentration of polyvinyl pyrrolidone is 100-200 mg / mL, and the number average molecular weight of polyvinyl pyrrolidone is 130 kDa.

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