A core-shell type microneedle with antibacterial and liquid absorption functions and a preparation method thereof

Abstract

This invention discloses a core-shell microneedle with both antibacterial and exudate-absorbing properties, and its preparation method, belonging to the field of microneedle drug delivery systems and acne treatment technology. The microneedle comprises: a core layer containing an exudate-absorbing component for absorbing exudate; and a shell layer covering the core layer, containing a microenvironment-responsive drug delivery unit and antibacterial nanoparticles loaded within the drug delivery unit. The drug delivery unit responds to the microenvironment of the acne lesion by releasing the antibacterial nanoparticles. This invention combines baicalein and surfactant into nanoparticles, loaded into a ROS-responsive shell layer formed by TSPBA and polyvinyl alcohol. Sodium polyglutamate is introduced into the core layer as an exudate-absorbing component. The core-shell microneedle is prepared by a two-step centrifugation method. This invention solves the problems of poor drug permeability, uncontrollable release, and exudate affecting treatment efficacy in traditional acne treatments. It achieves targeted drug release and exudate adsorption synergistic effects on acne lesions, improves drug bioavailability, reduces systemic side effects, and is suitable for the treatment of acne, especially inflammatory and purulent acne.

Description

Technical Field

[0001] This invention belongs to the interdisciplinary field of microneedle drug delivery systems and skin disease treatment technology, specifically involving a core-shell microneedle that combines antibacterial and exudate absorption and its preparation method. Background Technology

[0002] Acne is a common chronic inflammatory skin disease of the pilosebaceous unit. Its pathogenesis is closely related to the proliferation of Propionibacterium acnes, excessive sebum secretion, abnormal keratinization of the pilosebaceous duct, and inflammatory response. The acne microenvironment (AME) of acne lesions has significant characteristics: First, the pH value is reduced. The normal skin pH is 5.5-7.0, while the pH of acne lesions drops to 4.5-6.0 due to the production of lactic acid, fatty acids, and other substances by Propionibacterium acnes metabolism. Second, specific enzymes are present. Propionibacterium acnes can secrete lipases, proteases, etc., which participate in sebum decomposition and inflammation mediation. Third, exudation occurs. Inflammatory acne (such as papules, pustules, and nodules) is often accompanied by exudate such as pus and tissue fluid, resulting in a moist lesion area with poor adhesion, which affects the retention and penetration of topical drugs.

[0003] Current acne treatments include topical medications (such as clindamycin and azelaic acid), oral medications (such as antibiotics and isotretinoin), and physical therapy. However, these treatments have several shortcomings: topical medications have poor skin permeability, making it difficult for them to penetrate the stratum corneum and reach the deep follicles and sebaceous glands, and their non-targeted release leads to low bioavailability; oral medications are prone to causing systemic side effects such as gastrointestinal discomfort and liver and kidney damage, and long-term use may lead to bacterial resistance; although traditional microneedling can disrupt the stratum corneum barrier and improve drug penetration, it lacks responsiveness to the acne microenvironment, making drug release uncontrollable and unable to handle lesion exudate. A moist environment can also cause the microneedles to not adhere tightly to the skin, affecting the treatment effect.

[0004] Baicalein, the core active ingredient of the traditional Chinese medicine Scutellaria baicalensis, exhibits unique advantages in acne treatment. It not only exerts direct antibacterial effects by disrupting the cell membrane integrity of Propionibacterium acnes and inhibiting bacterial biofilm formation, but also inhibits abnormal keratinization of the pilosebaceous duct by downregulating the expression of inflammatory factors such as TNF-α and IL-6, while simultaneously reducing sebum secretion, achieving a synergistic therapeutic effect of antibacterial, anti-inflammatory, and sebum metabolism regulation. However, baicalein has extremely poor water solubility and strong lipid solubility, resulting in low skin penetration when applied topically. Furthermore, it is easily metabolized and degraded in normal skin, limiting its bioavailability and restricting its clinical application.

[0005] Surfactin, derived from Bacillus subtilis, is a natural lipopeptide biosurfactant with multiple functions suitable for acne treatment: its amphiphilic structure can disrupt the cell membrane stability of pathogenic bacteria such as Propionibacterium acnes, exhibiting broad-spectrum antibacterial activity and being less likely to induce bacterial resistance. Furthermore, surfactant can reduce the interfacial tension between drugs and skin, improve the solubility and skin penetration of hydrophobic drugs (such as baicalein), and possesses advantages such as high biocompatibility, biodegradability, and no skin irritation.

[0006] Therefore, developing a new acne treatment formulation that can overcome the above-mentioned defects and has both targeted drug delivery and exudation management functions is of great clinical significance. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of the prior art and provide a core-shell microneedle that combines antibacterial and exudate absorption, as well as its preparation method.

[0008] To achieve the above objectives, the present invention provides the following technical solution: This application provides a core-shell microneedle that combines antibacterial and exudate absorption properties, the microneedle comprising: The core layer contains an exudate-absorbing component for absorbing exudate; A shell, covering the outside of the core layer, includes a microenvironment-responsive drug delivery unit and antibacterial nanoparticles loaded within the drug delivery unit; The drug delivery unit releases the antibacterial nanoparticles in response to the acne lesion microenvironment.

[0009] Optionally, the antibacterial nanoparticles are surfactant-baicalin composite nanoparticles.

[0010] Optionally, the surfactant-baicalin composite nanoparticles are formed by covalently combining surfactant and baicalin.

[0011] Optionally, the microenvironment-responsive drug delivery unit is a reactive oxygen species (ROS) responsive unit.

[0012] Optionally, the ROS-responsive unit is formed by covalently bonding a phenylboronic acid ester crosslinking agent with a polymer matrix.

[0013] Optionally, the phenylboronic acid ester crosslinking agent is TSPBA, and the polymer matrix is ​​polyvinyl alcohol (PVA).

[0014] Optionally, the permeate-absorbing component is sodium polyglutamate.

[0015] Secondly, this application provides a method for preparing the above-mentioned core-shell microneedles, comprising the following steps: Provide microneedle molds; A shell solution containing antibacterial nanoparticles and microenvironment-responsive drug delivery unit molding material is injected into the microneedle mold and subjected to a first curing treatment to form the shell of the microneedle. A core layer solution containing exudate-absorbing components is injected into a microneedle mold that has undergone a first curing treatment, and then a second curing treatment is performed to form the core layer of the microneedle. Demolding yields the core-shell microneedles.

[0016] Optionally, the shell solution comprises polyvinyl alcohol (PVA), TSPBA, and surfactant-baicalin composite nanoparticles; the core solution comprises polyvinyl alcohol and sodium polyglutamate.

[0017] Thirdly, this application provides the use of the core-shell microneedles as described above or prepared by the above method in the preparation of drugs for treating skin diseases, especially acne.

[0018] Compared with the prior art, this application has the following beneficial effects: 1. This invention provides a novel composite nanoparticle that utilizes amphiphilic materials to treat hydrophobic drugs, combining the two through hydrogen bonds and hydrophilic-hydrophobic interactions to prepare a multifunctional nanoparticle. This significantly improves the hydrophilicity and dispersion stability of baicalin, while integrating the antibacterial, anti-inflammatory, and penetration-enhancing functions of both, thereby greatly improving the targeted therapy effect.

[0019] 2. This invention provides a drug delivery unit microneedle that can precisely penetrate the stratum corneum to construct a drug delivery channel, achieve local drug enrichment, avoid systemic side effects, and significantly improve treatment efficacy and patient compliance.

[0020] 3. The ROS-responsive and exudate-absorbing structural design provided by this invention enables the drug to be specifically released only in the microenvironment of acne lesions, with extremely low drug release in normal skin areas, significantly improving drug bioavailability, reducing systemic side effects, and avoiding the development of bacterial resistance; at the same time, the exudate-absorbing component can quickly absorb lesion exudate, improve the moist environment, and prolong the contact time between the microneedle and the skin, prolonging the drug action time and improving penetration efficiency.

[0021] 4. All components used in this invention are biocompatible materials, non-irritating, and have no obvious toxic side effects, avoiding the biotoxicity problems of traditional drug carriers; the microneedle length is precisely controlled within the traditional range of the stratum corneum, with no obvious pain or skin damage.

[0022] 5. It can be loaded with a variety of antibacterial and anti-inflammatory drugs, making it suitable for the treatment of different types of acne. It requires no special equipment and has a simple preparation process. Attached Figure Description

[0023] Figure 1 This is a TEM image of the synthesized surfactant-baicalin composite nanoparticles.

[0024] Figure 2 This is a particle size distribution diagram of the synthesized surfactant-baicalin composite nanoparticles.

[0025] Figure 3 The drug release curves after the synthesis of surfactant-baicalin composite nanoparticles are shown.

[0026] Figure 4 The infrared spectrum of the synthesized surfactant-baicalin composite nanoparticles is shown.

[0027] Figure 5 This is a differential calorimetric scanning spectrum of the synthesized surfactant-baicalin composite nanoparticles.

[0028] Figure 6 This image shows the antibacterial effect of the synthesized surfactant-baicalin composite nanoparticles.

[0029] Figure 7 This is a SEM image of the microneedles.

[0030] Figure 8 This is a fluorescence image of the microneedles. Detailed Implementation

[0031] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0032] Furthermore, in this invention, an element referred to as fixed to or disposed on another element may be directly disposed on the other element, or there may be an intermediate element. When an element is considered to be connected to another element, it may be directly connected to the other element, or there may be an intermediate element present simultaneously. The terms vertical, horizontal, left, right, and similar expressions used herein are for illustrative purposes only and do not represent the only possible implementation.

[0033] Example 1 See Figures 1-8 This application provides a core-shell microneedle that combines antibacterial and exudate absorption properties, the microneedle comprising: The core layer contains an exudate-absorbing component for absorbing exudate; A shell, covering the outside of the core layer, includes a microenvironment-responsive drug delivery unit and antibacterial nanoparticles loaded within the drug delivery unit; The drug delivery unit releases the antibacterial nanoparticles in response to the acne lesion microenvironment.

[0034] In this embodiment, the microneedles prepared in this embodiment include a core layer and a shell layer; the core layer contains sodium polyglutamate as an exudate absorption component; the shell layer covers the outside of the core layer and contains a ROS-responsive drug delivery unit (a borate ester bond crosslinking network formed by TSPBA and PVA) and surfactant-baicalin composite nanoparticles loaded in the unit.

[0035] Furthermore, using a PDMS microneedle mold, a shell solution (containing TSPBA, PVA, and SF@BA nanoparticles) and a core solution (containing PVA and sodium polyglutamate) were injected sequentially through a two-step centrifugation method. After two freeze-drying processes, the core-shell microneedle array was obtained by demolding.

[0036] Furthermore, to verify the core-shell structure, Rhodamine B (a red fluorescent dye) was added to the core layer solution, and FITC (a green fluorescent dye) was added to the shell layer solution. Microneedles were prepared using the same method; fluorescence microscopy observations showed (same as above) Figure 8 The inner layer of the microneedles exhibits red fluorescence, while the outer layer exhibits green fluorescence, demonstrating the successful construction of a core-shell structure in which the core layer is enclosed within the shell layer.

[0037] To verify the exudate absorption function, a microneedle array was attached to the surface of an aqueous agarose gel to simulate an exudate environment, and the mass increase at different time points was measured. The results showed that the microneedles containing sodium polyglutamate absorbed 3.5 times their own weight of water within 30 minutes, which was significantly higher than the control group without sodium polyglutamate (absorbing only 1.2 times the amount of water), proving that the core layer has good exudate absorption capacity.

[0038] To verify the responsive release function of the drug delivery unit, microneedles were placed in PBS buffer containing 100 μM H2O2 (simulating the high ROS microenvironment of acne) and ordinary PBS buffer (simulating the normal skin environment), and the release of baicalin was measured. The results showed that in the high ROS environment, the cumulative drug release rate reached 78.5% within 24 hours, while in the ordinary environment, only 23.6% was released, demonstrating that the drug delivery unit can respond to the acne lesion microenvironment and achieve targeted release.

[0039] Optionally, the antibacterial nanoparticles are surfactant-baicalin composite nanoparticles; the surfactant-baicalin composite nanoparticles are formed by the covalent bonding of surfactant and baicalin.

[0040] Preparation of surfactant-baicalein composite nanoparticles: 4 mg of surfactant and 2 mg of baicalein were accurately weighed and dissolved in 0.4 mL of acetone. The solution was then added dropwise to 4 mL of ultrapure water stirred at 800 rpm. The mixture was stirred in the dark for 4 hours to obtain a dispersion of SF@BA composite nanoparticles. The dispersion was observed under a transmission electron microscope (TEM). Figure 1 The particles were observed to be spherical with uniform size and no obvious aggregation, proving the successful preparation of nanoparticles. Fourier transform infrared spectroscopy analysis was performed on freeze-dried SF, BA, and SF@BA powders (same as above). Figure 4 The results showed that characteristic absorption peaks of both SF and BA appeared simultaneously in the SF@BA complex, and some peak positions shifted, indicating an interaction between the two. Differential scanning calorimetry (DSC) was performed. Figure 5 The results show that the thermal behavior of the SF@BA complex differs significantly from that of a physical mixture of the two. These results demonstrate that the surfactant and baicalin covalently combine to form nanoparticles.

[0041] Optionally, the microenvironment-responsive drug delivery unit is a reactive oxygen species (ROS) responsive unit; the ROS responsive unit is formed by a phenylboronic acid ester crosslinking agent and a polymer matrix through covalent bonds; the phenylboronic acid ester crosslinking agent is TSPBA, and the polymer matrix is ​​polyvinyl alcohol (PVA).

[0042] Preparation of the shell solution: TSPBA was dissolved in ultrapure water to prepare a 3% (w / w) TSPBA solution; the concentration of the above SF@BA composite nanoparticle dispersion was adjusted to 200 μg / mL; the TSPBA solution and nanoparticle dispersion were mixed in equal volumes to obtain the shell solution. The shell solution was injected separately into a mold and freeze-dried to form a ROS-responsive unit; this unit was used for swelling experiments, placed in PBS buffers containing 0 μM, 50 μM, and 100 μM H2O2 respectively. To verify the specific structure of the responsive unit, a gel was formed immediately after mixing the TSPBA solution and PVA solution, proving that the two are cross-linked through borate ester bonds. The gel was placed in H2O2 solution, and the gel gradually dissolved, further demonstrating the ROS-responsive breaking characteristics of the borate ester bonds.

[0043] Optionally, the permeate-absorbing component is sodium polyglutamate.

[0044] Preparation of the core layer solution: Polyvinyl alcohol (PVA, degree of polymerization 1750±50) and sodium polyglutamate (molecular weight 500,000-800,000) were weighed and dissolved in ultrapure water to prepare a mixed solution with a total mass fraction of 10%, of which PVA accounted for 7.5% and sodium polyglutamate for 2.5%. To verify the permeation absorption function of sodium polyglutamate, a control core layer solution (containing only 10% PVA, without sodium polyglutamate) was prepared, and two types of microneedles were prepared accordingly. The two types of microneedles were attached to the surface of hydrous agarose gel, and the water absorption was measured. The results showed that the microneedles containing sodium polyglutamate absorbed 4.2 times the amount of water within 60 minutes, while the control group without sodium polyglutamate only absorbed 1.5 times. Sodium polyglutamate is rich in free carboxyl groups and has extremely strong hydrophilic properties, adsorbing a large number of water molecules.

[0045] Secondly, this application provides a method for preparing the above-mentioned core-shell microneedles, comprising the following steps: Provide microneedle molds; A shell solution containing antibacterial nanoparticles and microenvironment-responsive drug delivery unit molding material is injected into the microneedle mold and subjected to a first curing treatment to form the shell of the microneedle. A core layer solution containing exudate-absorbing components is injected into a microneedle mold that has undergone a first curing treatment, and then a second curing treatment is performed to form the core layer of the microneedle. Demolding yields the core-shell microneedles.

[0046] Optionally, the shell solution comprises polyvinyl alcohol (PVA), TSPBA, and surfactant-baicalin composite nanoparticles; the core solution comprises polyvinyl alcohol and sodium polyglutamate.

[0047] In this embodiment, the steps for preparing the microneedles include: Provide PDMS microneedle molds (tip height 600μm, bottom diameter 300μm, array 10×10); The shell solution (containing TSPBA, PVA and SF@BA nanoparticles) was added to the surface of the mold and centrifuged at 3000 rpm for 10 minutes to fill the microcavity of the mold. The solution was then freeze-dried at -50℃ for 24 hours to form the shell of the microneedles (first curing treatment). The core layer solution (containing PVA and sodium polyglutamate) was added to the surface of the same mold and centrifuged at 3000 rpm for 10 minutes to fill the cavity inside the shell layer. The core layer solution was then freeze-dried at -50°C for 24 hours to form the core layer of the microneedles (second curing treatment). Carefully demold at room temperature to obtain a core-shell microneedle array.

[0048] The above steps fully realize the preparation process of first forming the shell and then forming the core.

[0049] Prepare the following solutions respectively: Shell solution: 3% TSPBA + 200 μg / mL SF@BA nanoparticles (mixed in equal volumes).

[0050] Core layer solution: 7.5% PVA + 2.5% sodium polyglutamate by mass fraction.

[0051] The microneedles prepared according to the above method were observed by SEM (same as above). Figure 7 The shape is regular, the surface is smooth, and there are no cracks; observation under a fluorescence microscope (same as above). Figure 8 The core-shell structure was confirmed; performance tests confirmed that it has both responsive drug release and exudate absorption functions.

[0052] Thirdly, this application provides the use of the core-shell microneedles as described above or prepared by the above method in the preparation of drugs for treating skin diseases, especially acne.

[0053] The core-shell microneedles prepared in this embodiment were subjected to in vitro transdermal and antibacterial experiments to verify their application potential in the preparation of drugs for treating acne.

[0054] In vitro transdermal assay: A Franz diffusion cell was used to press a microneedle array onto isolated porcine skin, with PBS buffer in the receiving cell. The control group consisted of ordinary microneedles (without response units and exudate absorption components) and direct application of SF@BA nanoparticle suspension. Receiving fluid was collected at 2, 4, 8, 12, and 24 hours to determine the baicalin content. Results showed that the core-shell microneedles of this invention achieved a cumulative drug penetration of 42.5 μg / cm² within 24 hours, significantly higher than that of ordinary microneedles (18.3 μg / cm²) and the direct application group (6.7 μg / cm²), demonstrating its ability to significantly improve drug penetration efficiency through the skin.

[0055] Antibacterial experiment: The antibacterial effect of SF@BA nanoparticles against Propionibacterium acnes was evaluated using the plate count method. Suspensions of Propionibacterium acnes were co-cultured with different concentrations of SF@BA and then spread onto solid culture medium. The mixture was anaerobically incubated at 37°C for 24 hours, and the colony count was performed after incubation. The results showed that the antibacterial effect of the SF@BA nanoparticles against Propionibacterium acnes was concentration-dependent, while the pure baicalin group showed no significant antibacterial effect, demonstrating that the SF@BA nanoparticles possess good antibacterial activity.

[0056] The above results indicate that the core-shell microneedles of the present invention can effectively deliver drugs through the skin and exert antibacterial effects at the site of action, making them suitable for the treatment of acne.

[0057] In summary, this embodiment has comprehensively prepared a core-shell microneedle that combines antibacterial properties and exudate absorption according to the provided technical solution, and verified the feasibility and beneficial effects of the technical solution of the present invention through a series of experiments.

[0058] Example 2 Preparation of surfactant-baicalin composite nanoparticles: Accurately weigh 4 mg of surfactant (SF) and 2 mg of baicalein (BA), and dissolve them together in 0.4 mL of acetone. Shake thoroughly to ensure complete dissolution of the solids, obtaining an organic phase solution. At room temperature, slowly inject this organic phase solution dropwise into 4 mL of ultrapure water stirred at 800 rpm using a syringe. The addition process should be carried out in the dark. After the addition is complete, continue stirring for 4 hours to allow the acetone to evaporate completely, yielding an aqueous dispersion of surfactant-baicalein composite nanoparticles (SF@BA). The obtained product can be further freeze-dried to obtain a solid powder, or directly used in the subsequent preparation of microneedles.

[0059] Example 3 Preparation of core-shell microneedles (1) Preparation of shell solution: Weigh TSPBA (phenylboronic acid ester crosslinking agent) and dissolve it in ultrapure water to prepare a 3% TSPBA solution; separately take the SF@BA composite nanoparticle dispersion prepared in Example 2 and adjust the concentration to 200 μg / mL. Mix the TSPBA solution and the nanoparticle dispersion in equal volumes to obtain shell mixed solution 2.

[0060] (2) Preparation of core layer solution: Weigh polyvinyl alcohol (PVA, degree of polymerization 1750±50) and sodium polyglutamate (molecular weight 500,000-800,000), dissolve them in ultrapure water, and prepare a mixed solution with a total mass fraction of 10%, of which the mass fraction of PVA is 7.5% and the mass fraction of sodium polyglutamate is 2.5%, to obtain core layer mixed solution 1.

[0061] (3) Microneedle Forming: A polydimethylsiloxane (PDMS) microneedle mold (tip height approximately 600 μm, bottom diameter approximately 300 μm, array 10 × 10) was used. First, the shell solution 2 prepared in step (1) was added to the surface of the mold and centrifuged at 3000 rpm for 10 minutes to fully fill the microcavities of the mold. After removal, the mold was placed in a vacuum drying oven and freeze-dried at -50°C for 24 hours to solidify the shell. Then, the core solution 1 prepared in step (2) was added to the same mold surface and centrifuged again at 3000 rpm for 10 minutes to fill the internal cavity of the formed shell with the core solution. Freeze-drying was performed again at -50°C for 24 hours. Finally, the mold was removed from the drying oven and carefully demolded at room temperature to obtain a drug-loaded microneedle array with a core-shell structure.

[0062] Example 4 The SF@BA composite nanoparticle dispersion prepared in Example 3 was characterized as follows: (1) Transmission electron microscopy (TEM) observation: The diluted dispersion was dropped onto a copper grid, allowed to dry naturally, and then the particle morphology was observed under TEM. The results are as follows: Figure 1 As shown, the particles are spherical, uniform in size, and show no obvious aggregation.

[0063] (2) Particle size distribution determination: The hydrated particle size and distribution of nanoparticles were determined using a dynamic light scattering particle size analyzer. The results are as follows: Figure 2 As shown, the average particle size is approximately 291 nm, and the polydispersity index (PDI) is less than 0.2, indicating a narrow particle size distribution.

[0064] (3) Drug release experiment: SF@BA nanoparticles were dispersed in PBS buffer at pH 7.4 and placed in a 37°C constant temperature shaker. Samples were taken at different time points to determine the amount of baicalin released. The results are as follows: Figure 3 As shown, under simulated internal environment conditions, baicalin can be released continuously, reaching a maximum release of 70% at 12 hours, while pure baicalin can only be released up to 15% at 4 hours due to its poor stability in water. This indicates that nanoparticles have the ability to stabilize baicalin and release it continuously.

[0065] (4) Fourier transform infrared spectroscopy (FTIR) analysis: Freeze-dried SF, BA, and SF@BA powders were compressed with KBr and subjected to infrared spectroscopy scanning. The results are as follows: Figure 4 As shown, the characteristic absorption peaks of SF and BA appeared simultaneously in the SF@BA complex, and some peak positions were shifted, indicating that there is an interaction between the two.

[0066] (5) Differential Scanning Calorimetry (DSC) Analysis: SF, BA, SF@BA, and physical mixtures thereof were subjected to DSC tests. Results are as follows: Figure 5 As shown, the thermal behavior of the SF@BA complex differs significantly from that of the raw materials, further confirming the formation of the complex.

[0067] (6) Antibacterial activity assay: The antibacterial effect of SF@BA nanoparticles on bacteria was evaluated using the plate count method. Bacterial suspensions were co-cultured with different concentrations of SF@BA and then spread onto solid culture media. Colony counts were performed after incubation. Results are shown below. Figure 6 As shown, SF@BA nanoparticles can effectively inhibit bacterial growth in a concentration-dependent manner.

[0068] Example 5: Structural Characterization and Performance Testing of Microneedles The core-shell microneedles prepared in Example 4 were subjected to the following tests: (1) Scanning electron microscopy (SEM) observation: The microneedle array was attached to the sample stage, sputtered with gold, and then its morphology was observed under SEM. The results are as follows: Figure 7 As shown, the microneedles are regularly shaped, have a smooth surface, sharp tips, and are free of cracks.

[0069] (2) Fluorescence microscopy observation: To verify the core-shell structure, the fluorescent dye Rhodamine B (red) was added to the core layer solution 2, and the fluorescent dye FITC (green) was added to the shell layer solution 1. Microneedles were prepared according to the method in Example 3, and then observed under a fluorescence microscope. The results are as follows: Figure 8 As shown, the outer layer of the microneedles exhibits green fluorescence, while the inner layer exhibits red fluorescence, indicating that the core-shell structure has been successfully constructed.

[0070] (3) Exudate absorption performance test: The microneedle array was attached to the surface of the aqueous agarose gel (simulating an exudate environment), and the mass increase of the microneedle array at different time points was measured to calculate the water absorption. The results showed that the water absorption of the microneedles containing sodium polyglutamate was significantly higher than that of the control group without sodium polyglutamate, indicating that it has good exudate absorption capacity.

[0071] (4) In vitro transdermal experiment: Using a Franz diffusion cell, the microneedle array was pressed onto isolated porcine skin, and the cumulative permeation amount of baicalin through the skin into the receiving fluid was measured. The results showed that compared with ordinary microneedles and direct application of drugs, the core-shell microneedles of the present invention can significantly improve the skin permeation of drugs, and the drug release is faster under high ROS conditions, proving that it has the characteristics of microenvironment-responsive release and enhanced permeation.

[0072] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered in all respects as exemplary and non-limiting, and the scope of the invention is defined by the appended claims rather than the foregoing description. Thus, all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the present invention. No reference numerals in the claims should be construed as limiting the scope of the claims.

[0073] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A core-shell microneedle that combines antibacterial and exudate absorption properties, characterized in that, The microneedles include: The core layer contains an exudate-absorbing component for absorbing exudate; A shell, covering the outside of the core layer, includes a microenvironment-responsive drug delivery unit and antibacterial nanoparticles loaded within the drug delivery unit; The drug delivery unit releases the antibacterial nanoparticles in response to the acne lesion microenvironment.

2. The core-shell microneedle according to claim 1, characterized in that, The antibacterial nanoparticles are surfactant-baicalin composite nanoparticles.

3. The core-shell microneedle according to claim 2, characterized in that, The surfactant-baicalin composite nanoparticles are formed by the covalent bonding of surfactant and baicalin.

4. The core-shell microneedle according to claim 1, characterized in that, The microenvironment-responsive drug delivery unit is a reactive oxygen species (ROS) responsive unit.

5. The core-shell microneedle according to claim 4, characterized in that, The ROS-responsive unit is formed by covalent bonds between a phenylboronic acid ester crosslinking agent and a polymer matrix.

6. The core-shell microneedle according to claim 5, characterized in that, The phenylboronic acid ester crosslinking agent is TSPBA, and the polymer matrix is ​​polyvinyl alcohol (PVA).

7. The core-shell microneedle according to claim 1, characterized in that, The permeate absorption component is sodium polyglutamate.

8. A method for preparing the core-shell microneedles as described in any one of claims 1 to 7, characterized in that, Includes the following steps: Provide microneedle molds; A shell solution containing antibacterial nanoparticles and microenvironment-responsive drug delivery unit molding material is injected into the microneedle mold and subjected to a first curing treatment to form the shell of the microneedle. A core layer solution containing exudate-absorbing components is injected into a microneedle mold that has undergone a first curing treatment, and then a second curing treatment is performed to form the core layer of the microneedle. Demolding yields the core-shell microneedles.

9. The preparation method according to claim 8, characterized in that, The shell solution contains polyvinyl alcohol (PVA), TSPBA, and surfactant-baicalin composite nanoparticles; the core solution contains polyvinyl alcohol and sodium polyglutamate.

10. The use of a core-shell microneedle as described in any one of claims 1 to 7, or a core-shell microneedle prepared by the preparation method according to claim 8 or 9, in the preparation of a medicament for treating skin diseases, particularly acne.

Images