PLGA-minoxidil microneedle with near-infrared response and preparation method of PLGA-minoxidil microneedle

Abstract

The invention discloses a PLGA (poly (lactic-co-glycolic acid))-minoxidil microneedle with near-infrared response and a preparation method of the PLGA-minoxidil microneedle. The PLGA-minoxidil microneedle with the near infrared response comprises PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles, a base body and a needle body, wherein the PLGA-minoxidil microspheres are arranged on the base body; wherein the PLGA-minoxidil microspheres and the lanthanum hexaboride nanoparticles are distributed in the needle body; and the base body and the needle body are made of a combination of PVA (polyvinyl alcohol) 1788 and PVA 1799. The PLGA-minoxidil microspheres are combined with the hydrogel microneedle with near-infrared response, controlled release of MXD is achieved on the microstructure through cooperation of the microporous structure of the microspheres and the near-infrared response effect of lanthanum hexaboride nanoparticles, the side effect of the medicine is effectively reduced, the concentration of the medicine in the body can be better maintained, and the drug delivery effect is improved. A better treatment effect is achieved; macroscopically, the prepared hydrogel system has relatively good mechanical properties, and can provide a stable drug delivery channel and drug delivery efficiency.

Description

Technical Field

[0001] The invention relates to the technical field of biomedical materials, and in particular to a PLGA-minoxidil microneedle with near-infrared response and a preparation method thereof. Background Art

[0002] Hair loss is common in both men and women and is often caused by physiological or pathological conditions, such as medications, trauma, stress, and autoimmune diseases. The most common form of hair loss is androgenetic alopecia (AGA), a chronic, progressive disease caused by high levels of testosterone, an androgen. Although AGA is not a serious, life-threatening disease, the changes in body and image caused by hair loss can significantly affect patients' psychological well-being and quality of life, making the development of effective AGA treatment strategies highly desirable.

[0003] Currently, the only two drugs approved by the U.S. Food and Drug Administration (FDA) for the treatment of AGA are oral finasteride and topical minoxidil (MXD), both of which require daily administration for more than 6 months. Since oral finasteride often causes systemic toxicity, most patients prefer MXD formulations for hair regrowth. However, these topical MXD solutions or foams usually have poor patient compliance and limited therapeutic efficacy due to frequent dosing (i.e., ∼180 doses) and low bioabsorption (i.e., <1%), which is caused by the physical barrier of the skin, the stratum corneum. Among the various methods to increase skin penetration and improve treatment efficiency, the use of MNs has received considerable attention due to their unique properties. Microneedles can effectively penetrate the stratum corneum of the skin for transdermal drug delivery, improve drug delivery efficiency, achieve self-administration, and do not cause any biohazardous waste. Among them, hydrogel-forming microneedles (HFMs) are composed of swellable polymers (cross-linked hydrogels) and can deliver drugs continuously for a long time by incorporating drugs into the polymer structure during the preparation process or loading drugs into a separate reservoir and attaching it to the HFM. However, achieving precise control over drug release rate and pattern is a challenge facing hydrogel microneedle technology.

[0004] Therefore, developing a microneedle that can be used for controlled release of minoxidil as a substitute for the above two existing preparations has great market value. Summary of the invention

[0005] The purpose of the present invention is to overcome the above technical deficiencies, propose a PLGA-minoxidil microneedle with near-infrared response and a preparation method thereof, and solve the technical problem that the release rate and pattern of the hydrogel microneedle to the drug in the prior art are difficult to control.

[0006] In the first aspect, the present invention provides a PLGA-minoxidil microneedle with near-infrared response, comprising: PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles, a matrix and a needle body; wherein the PLGA-minoxidil microspheres and lanthanum hexaboride nanoparticles are distributed in the needle body; the material of the matrix and the needle body is a combination of PVA 1788 and PVA 1799.

[0007] In a second aspect, the present invention provides a method for preparing a PLGA-minoxidil microneedle with near infrared response, comprising the following steps: Providing PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles and a first polyvinyl alcohol aqueous solution; PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles and a first polyvinyl alcohol aqueous solution are mixed evenly and poured into a microneedle mold, followed by a first centrifugation and drying to obtain PLGA-minoxidil microneedles with near-infrared response; wherein the first polyvinyl alcohol aqueous solution is obtained by dissolving PVA 1788 and PVA 1799 in water.

[0008] Compared with the prior art, the beneficial effects of the present invention include: The present invention combines PLGA-minoxidil microspheres with hydrogel microneedles with near-infrared response, and achieves controlled release of MXD through the cooperation of the microporous structure of the microspheres and the near-infrared response of lanthanum hexaboride nanoparticles in the microstructure, and effectively reduces the side effects of the drug, can better maintain the drug concentration in the body, and achieve better therapeutic effects; macroscopically, the prepared hydrogel system has good mechanical properties and can provide a stable drug delivery channel and drug delivery efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1 A schematic structural diagram of an embodiment of a PLGA-minoxidil microneedle with near-infrared response provided by the present invention; Figure 2 The scanning electron microscope image of the PLGA-minoxidil microspheres prepared in the present invention with a molar ratio of lactic acid to glycolic acid of 50:50; Figure 3 The scanning electron microscope image of the PLGA-minoxidil microspheres prepared in the present invention with a molar ratio of lactic acid to glycolic acid of 75:25; Figure 4 A physical picture of a PVA hydrogel microneedle prepared with a mass ratio of PVA (type 1788) to PVA (type 1799) of 6:4 and a microscopic picture of the needle tip; Figure 5 A physical picture of a PVA hydrogel microneedle prepared with a mass ratio of PVA (type 1788) to PVA (type 1799) of 7:3 and a microscopic picture of the needle tip in the present invention; Figure 6 This is a melting image of the PLGA-minoxidil microneedle with near-infrared response prepared in Example 1 of the present invention after being irradiated with near-infrared light for 10 seconds; Figure 7 This is a melting image of the PLGA-minoxidil microneedle with near-infrared response prepared in Comparative Example 1 of the present invention after being irradiated with near-infrared light for 10 seconds; Figure 8 This is a melting image of the PLGA-minoxidil microneedle with near-infrared response prepared in Comparative Example 2 of the present invention after being irradiated with near-infrared light for 10 seconds; Fig. 9 This is an image of the cumulative drug release of the PLGA-minoxidil microneedle with near-infrared response prepared in Example 1 of the present invention under near-infrared light irradiation and without near-infrared light irradiation. DETAILED DESCRIPTION

[0010] In order to make the purpose, technical solution 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.

[0011] See also Figure 1 In the first aspect, the present invention provides a PLGA-minoxidil microneedle with near-infrared response, comprising: PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles, a matrix and a needle body; wherein the PLGA-minoxidil microspheres and lanthanum hexaboride nanoparticles are distributed in the needle body; the material of the matrix and the needle body is a combination of PVA 1788 and PVA 1799.

[0012] The crystal structure of lanthanum hexaboride is CsCl structure, which belongs to the simple cubic crystal system. It is a rare earth boride with the molecular formula LaB6. LaB6 has many superior properties, such as electron emission intensity, radiation resistance, high-temperature chemical stability, etc., which makes it widely used in many high-tech fields. By utilizing the absorption and scattering effect of nano-scale LaB6 in the near-infrared band, it has the characteristics of near-infrared absorption and can be used in sensors, microelectronic machinery, optical films and other fields. Compared with other photothermal materials, LaB6 has high photothermal conversion efficiency and low cost. After absorbing near-infrared light, the temperature is about 50°C, which can match the melting point of PVA hydrogel microneedles and will not cause thermal damage to the skin.

[0013] The present invention uses minoxidil as a drug for treating androgenic alopecia, and uses PLGA to load MXD to form microspheres, which are combined with microneedles with near-infrared light response to achieve sustained release and controlled release of MXD, thereby improving bioavailability and reducing side effects of MXD. Among them, the PVA hydrogel material for making the needle body is composed of low-saponified PVA and high-saponified PVA, which can effectively improve the shortcomings of single PVA as a needle body material, thereby penetrating the stratum corneum of the skin and opening a drug delivery channel. Compared with traditional drug delivery methods, the drug delivery method of this microneedle system can carry out targeted delivery while reducing skin irritation, achieving better therapeutic effects, and improving patients' mental health and quality of life.

[0014] In this embodiment, the average particle size of the PLGA-minoxidil microspheres is 8-12 μm.

[0015] In this embodiment, the average particle size of the lanthanum hexaboride nanoparticles is 20-50 nm.

[0016] In this embodiment, the mass ratio of PVA 1788 to PVA 1799 is (1.2-1.8): 1, further 1.5: 1. A single low-saponification PVA hydrogel will result in insufficient mechanical strength of the needle body, while a single high-saponification PVA hydrogel will make it difficult to shape the needle body. The present invention combines the advantages of the two PVAs with two saponification degrees in the above ratio, so that the microneedle has both the mechanical strength to penetrate the human skin and the advantage of easy molding. In addition, the melting point of the microneedle can be within the temperature range of the heat emitted by the near-infrared material absorbing near-infrared light.

[0017] In a second aspect, the present invention provides a method for preparing a PLGA-minoxidil microneedle with near infrared response, comprising the following steps: S1, providing PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles and a first polyvinyl alcohol aqueous solution; S2. The PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles and the first polyvinyl alcohol aqueous solution are mixed evenly and poured into a microneedle mold, followed by a first centrifugation and drying to obtain PLGA-minoxidil microneedles with near-infrared response; wherein the first polyvinyl alcohol aqueous solution is obtained by dissolving PVA 1788 and PVA 1799 in water.

[0018] In this embodiment, in step S1, the preparation steps of PLGA-minoxidil microspheres include: S11, preparing a second polyvinyl alcohol aqueous solution; S12, preparing a minoxidil glacial acetic acid solution and a polylactic acid-co-glycolic acid (PLGA) ethyl acetate (EA) solution, and uniformly mixing the minoxidil glacial acetic acid solution, the polylactic acid-co-glycolic acid ethyl acetate solution and chloroform to obtain an organic phase; S13, mixing the second polyvinyl alcohol aqueous solution and the organic phase uniformly to form an O / W emulsion, followed by stirring, a second centrifugation, washing, and drying to obtain PLGA-minoxidil microspheres.

[0019] Wherein, in step S11, in the second polyvinyl alcohol aqueous solution, the second polyvinyl alcohol is PVA 1788, and the mass fraction of the second polyvinyl alcohol is 15%-25%, and further is 20%.

[0020] Wherein, in step S11, during the preparation of the second polyvinyl alcohol aqueous solution, the dissolution temperature is 80-100°C.

[0021] Wherein, in step S12, the concentration of minoxidil in the glacial acetic acid solution of minoxidil is 0.5-1 mg / uL, further 0.75 mg / uL.

[0022] Wherein, in step S12, during the process of preparing the glacial acetic acid solution of minoxidil, the dissolution temperature is -10~0°C and the dissolution time is 30-60min.

[0023] Wherein, in step S12, the concentration of PLGA in the ethyl acetate solution of poly(lactic acid-co-glycolic acid) is 2-5 mg / uL, and further 3.6 mg / uL.

[0024] Wherein, in step S12, the molar ratio of lactic acid to glycolic acid in the polylactic acid-glycolic acid copolymer is (0.8-1.2):1, further 1:1.

[0025] Wherein, in step S12, in the organic phase, the mass ratio of minoxidil to polylactic acid-glycolic acid copolymer is 1:(1-1.5), further 1:1.2; the volume ratio of ethyl acetate to chloroform is 1:(18-20), further 1:19.

[0026] Wherein, in step S13, during the process of uniformly mixing the second polyvinyl alcohol aqueous solution and the organic phase, the temperature is -10~0°C.

[0027] Wherein, in step S13, a homogenizer is used to uniformly mix the second polyvinyl alcohol aqueous solution and the organic phase to form an O / W emulsion.

[0028] Furthermore, the rotation speed of the homogenizer is 5000-8000 rpm, further 6000 rpm, and the homogenization time is 120-300 s, further 180 s.

[0029] Wherein, in step S13, the stirring temperature is room temperature and the stirring time is 7-8 hours. The present invention can evaporate the organic solvent by controlling the stirring time within the above range.

[0030] The rotation speed of the second centrifugation is 4000-5000 rpm, further 4200 rpm, and the time of the second centrifugation is 10-20 min, further 15 min.

[0031] Wherein, in step S13, the washing method is washing with deionized water.

[0032] Wherein, in step S13, the drying method is freeze-drying.

[0033] In this embodiment, in step S1, the mass fraction of the first polyvinyl alcohol aqueous solution is 8%-12%, and further is 10%.

[0034] In this embodiment, in step S1, during the preparation of the first polyvinyl alcohol aqueous solution, the dissolution temperature is 80-100°C.

[0035] In this embodiment, in step S2, the usage ratio of the first polyvinyl alcohol aqueous solution to the lanthanum hexaboride nanoparticles is 1 ml: (4-6) mg, further 1 ml: 5 mg.

[0036] In this embodiment, in step S2, the usage ratio of the first polyvinyl alcohol aqueous solution to the PLGA-minoxidil microspheres is 1 ml: (40-60) mg, further 1 ml: 50 mg.

[0037] In this embodiment, the rotation speed of the first centrifugation is 4000-5000 rpm, further 4200 rpm, and the time of the first centrifugation is 3-10 min, further 5 min.

[0038] In this embodiment, the drying temperature is 30-40° C., and the drying time is 1-3 hours.

[0039] Screening test 1 Screening of the molar ratio of lactic acid to glycolic acid Screening test 1-1 2g of PVA (type 1788) solid powder was dissolved in 8ml of pure water at 100°C, and after complete dissolution, it was allowed to stand and cooled to room temperature. 300mg of MXD was dissolved in 400uL of glacial acetic acid; 360mg of PLGA (lactic acid: glycolic acid molar ratio of 50:50) was dissolved in 100uL of ethyl acetate (EA), and then mixed with 1.9mL of trichloromethane (TCM) and glacial acetic acid solution of minoxidil to form an organic phase. The organic phase was mixed with the obtained 20% PVA aqueous solution, and then homogenized at 6000rpm for 180s using a homogenizer to form an O / W emulsion, stirred at room temperature for 7-8 hours to evaporate the organic solvent, and the microspheres were collected by centrifugation at 4200rpm for 15 minutes, and washed 4 times with deionized water. The sample was freeze-dried, and the obtained white powder was stored in the refrigerator until use.

[0040] Screening test 1-2 Compared with the screening test 1-1, the only difference is that the molar ratio of lactic acid:glycolic acid is 75:25.

[0041] See also Figure 2 and 3 ,pass Figure 2 and 3 It can be seen that the morphology of microspheres prepared by different molar ratios of lactic acid to glycolic acid in PLGA is also different. When the molar ratio of lactic acid to glycolic acid in PLGA is 75:25, the microspheres prepared have partial defects; while when the molar ratio of lactic acid to glycolic acid in PLGA is 50:50, the microspheres prepared have a smooth surface and regular shape. The reason may be that when lactic acid: glycolic acid = 50:50 in PLGA, it has a lower intrinsic viscosity and better hydrophilicity. It can be concluded that the optimal molar ratio of lactic acid to glycolic acid in PLGA-minoxidil microspheres is 50:50.

[0042] Screening test 2 Screening of the mass ratio of PVA (type 1788) to PVA (type 1799) Screening test 2-1 Take 0.6g PVA (1788 type) and 0.4g PVA (1799 type) and mix them, then pour them into a beaker containing 9ml pure water, heat them in an oil bath to 100°C for 30min, and cool them to room temperature after they are completely dissolved to obtain a composite PVA aqueous solution. Pour the composite PVA aqueous solution into a mold, centrifuge it at 4200rpm for 5min in a centrifuge, take out the sample, and store it in an oven at 30°C for 2 hours to obtain a thin film MN patch.

[0043] Screening test 2-2 The only difference compared to the screening test 2-1 is that 0.7 g of PVA (1788 type) and 0.3 g of PVA (1799 type) were mixed.

[0044] See also Figure 4-5 ,pass Figure 4-5 It can be seen that the microneedles made with PVA (1788 type): PVA (1799 type) = 7:3 have low mechanical strength and the needle body is bent, while the microneedles made with PVA (1788 type): PVA (1799 type) = 6:4 have very good mechanical strength. It can be concluded that the optimal mass ratio of low saponification to high saponification in PVA hydrogel is 6:4.

[0045] Example 1 Preparation of PLGA-minoxidil microneedles with near-infrared response 500 mg of PLGA-minoxidil microspheres obtained in screening experiment 1-1 and 50 mg of lanthanum hexaboride nanoparticles were stirred and mixed evenly in 10 ml of composite PVA aqueous solution obtained in screening experiment 2-1. Poured into a mold, centrifuged at 4200 rpm for 5 min, took out the sample, and stored in an oven at 30°C for 2 hours to obtain a thin film MN patch.

[0046] Comparative Example 1 Compared with Example 1, the only difference is that the added amount of lanthanum hexaboride nanoparticles is 20 mg.

[0047] Comparative Example 2 Compared with Example 1, the only difference is that the added amount of lanthanum hexaboride nanoparticles is 80 mg.

[0048] Performance Testing Utilizing the near-infrared response characteristics of LaB6 nanoparticles, the microneedles were irradiated with 808nm near-infrared light for 10s, and the morphology of the microneedles was observed to determine the near-infrared response changes of the prepared microneedles; the microneedles of Example 1 were placed in PBS, irradiated with 808nm near-infrared light, and then the samples were analyzed with a UV-visible spectrophotometer to establish the drug release (%)-time (h) curve of MXD-MPs-MN, and to verify the drug release of the microneedles with or without near-infrared light irradiation.

[0049] See also Figure 6-8 ,pass Figure 6-8 It can be seen that the microneedle prepared by adding 50 mg of lanthanum hexaboride nanoparticles into 10 ml of composite PVA aqueous solution has a micro-melting at the tip after 10 seconds of near-infrared light irradiation, indicating that the near-infrared response is good and can play a role in sustained release ( Figure 6 ); When 20 mg of lanthanum hexaboride nanoparticles were added to 10 ml of composite PVA aqueous solution, the microneedle was irradiated with near-infrared light for 10 seconds, and the needle body was almost not melted, and could not release the drug ( Figure 7); When 80 mg of lanthanum hexaboride nanoparticles were added to 10 ml of composite PVA aqueous solution, the microneedle was almost completely melted after 10 seconds of near-infrared light irradiation, and could not play a sustained release role ( Figure 8 ). It can be concluded that the optimal mass of lanthanum hexaboride nanoparticles added to 10 ml of composite PVA aqueous solution is 50 mg.

[0050] See also Fig. 9 ,pass Fig. 9 It can be seen that under near-infrared light irradiation conditions, the cumulative release of the drug from the microneedles in PBS can reach 90% within 2 hours, and the cumulative release of the drug within 120 hours can reach almost 100%; while without near-infrared light irradiation conditions, the cumulative release of the drug within 120 hours is only within 30%, indicating that the near-infrared responsive PLGA-minoxidil microsphere microneedles of the present invention can achieve the controlled release of MXD and improve the drug delivery efficiency.

[0051] Compared with the prior art, the beneficial effects of the present invention include: (1) The microneedles of the present invention can penetrate the stratum corneum of the skin to deliver drugs, thereby improving the efficiency of drug delivery. The PLGA microspheres can both load MXD and reduce its side effects; (2) The microneedle of the present invention introduces a near-infrared response system, the photocatalyst of which is LaB6 (20-50nm). When irradiated with near-infrared light, LaB6 absorbs laser energy and converts it into heat, inducing MN melting at 48.10°C, thereby triggering the release of PLGA minoxidil microspheres from MN, enabling controlled and sustained release of the drug, maintaining the drug concentration in the body, and thus achieving the effect of treating androgenic alopecia.

[0052] (3) The wavelength of the near-infrared light applicable to the microneedles of the present invention is 808 nm. Since the microneedles of the present invention act on the scalp in a small range, the near-infrared light used for treatment needs to be easily available and easy to carry, and this wavelength is the wavelength of the most easily available near-infrared light source (near-infrared flashlight) on the market. Therefore, the PLGA-minoxidil microneedles with near-infrared response of the present invention have high practical value.

[0053] The specific implementation of the present invention described above does not constitute a limitation on the protection scope of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A PLGA-minoxidil microneedle with near infrared response, characterized in that: include: PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles, matrix and needle body; wherein, The PLGA-minoxidil microspheres and the lanthanum hexaboride nanoparticles are distributed in the needle body; The material of the base and the needle body is a combination of PVA 1788 and PVA 1799.

2. The PLGA-minoxidil microneedle with near infrared response according to claim 1, characterized in that: The average particle size of the PLGA-minoxidil microspheres is 8-12 μm; the average particle size of the lanthanum hexaboride nanoparticles is 20-50 nm.

3. The PLGA-minoxidil microneedle with near infrared response according to claim 1, characterized in that: The mass ratio of the PVA1788 to the PVA 1799 is (1.2-1.8):

1.

4. A method for preparing PLGA-minoxidil microneedles with near infrared response as claimed in any one of claims 1 to 3, characterized in that: The following steps are involved: Providing PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles and a first polyvinyl alcohol aqueous solution; The PLGA-minoxidil microspheres, the lanthanum hexaboride nanoparticles and the first polyvinyl alcohol aqueous solution are uniformly mixed and poured into a microneedle mold, followed by first centrifugation and drying to obtain a PLGA-minoxidil microneedle with near-infrared response; wherein, The first polyvinyl alcohol aqueous solution is obtained by dissolving PVA 1788 and PVA 1799 in water.

5. The method for preparing PLGA-minoxidil microneedles with near infrared response according to claim 4, characterized in that: The preparation steps of the PLGA-minoxidil microspheres include: preparing a second polyvinyl alcohol aqueous solution; A glacial acetic acid solution of minoxidil and an ethyl acetate solution of a polylactic acid-co-glycolic acid copolymer are prepared, and the glacial acetic acid solution of minoxidil, the ethyl acetate solution of the polylactic acid-co-glycolic acid copolymer and chloroform are uniformly mixed to obtain an organic phase; The second polyvinyl alcohol aqueous solution and the organic phase are mixed uniformly to form an O / W emulsion, which is then stirred, centrifuged for a second time, washed, and dried to obtain PLGA-minoxidil microspheres.

6. The method for preparing PLGA-minoxidil microneedles with near infrared response according to claim 5, characterized in that: In the second polyvinyl alcohol aqueous solution, the second polyvinyl alcohol is PVA 1788, and the mass fraction of the second polyvinyl alcohol is 15%-25%; In the glacial acetic acid solution of minoxidil, the concentration of minoxidil is 0.5-1 mg / uL; In the ethyl acetate solution of the polylactic acid-co-glycolic acid copolymer, the concentration of the polylactic acid-co-glycolic acid copolymer is 2-5 mg / uL; In the organic phase, the mass ratio of minoxidil to polylactic acid-glycolic acid copolymer is 1:(1-1.5), and the volume ratio of ethyl acetate to chloroform is 1:(18-20).

7. The method for preparing PLGA-minoxidil microneedles with near infrared response according to claim 5, characterized in that: During the process of uniformly mixing the second polyvinyl alcohol aqueous solution and the organic phase, the temperature is -10 to 0 °C; Using a homogenizer to mix the second polyvinyl alcohol aqueous solution and the organic phase to form an O / W emulsion, the speed of the homogenizer is 5000-8000 rpm, and the homogenization time is 120-300 s; The stirring temperature is room temperature, and the stirring time is 7-8h; The speed of the second centrifugation is 4000-5000 rpm, and the time of the second centrifugation is 10-20 min; The washing method is deionized water washing; The drying method is freeze drying.

8. The method for preparing PLGA-minoxidil microneedles with near infrared response according to claim 4, characterized in that: The mass fraction of the first polyvinyl alcohol aqueous solution is 8%-12%.

9. The method for preparing PLGA-minoxidil microneedles with near infrared response according to claim 4, characterized in that: The dosage ratio of the first polyvinyl alcohol aqueous solution to the lanthanum hexaboride nanoparticles is 1 ml: (4-6) mg; the dosage ratio of the first polyvinyl alcohol aqueous solution to the PLGA-minoxidil microspheres is 1 ml: (40-60) mg.

10. The method for preparing PLGA-minoxidil microneedles with near infrared response according to claim 4, characterized in that: The rotation speed of the first centrifugation is 4000-5000 rpm, and the time of the first centrifugation is 3-10 min; the temperature of the drying is 30-40° C., and the time of the drying is 1-3 h.

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