A PLGA-minoxidil microneedle with near-infrared response and its preparation method

Abstract

The present invention discloses a PLGA-minoxidil microneedle with near-infrared response and a preparation method thereof. The PLGA-minoxidil microneedle with near-infrared response comprises: 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; and the materials of the matrix and the needle body are a combination of PVA 1788 and PVA 1799. The present invention combines PLGA-minoxidil microspheres with hydrogel microneedles with near-infrared response. In terms of microstructure, the microporous structure of the microspheres and the near-infrared response of the lanthanum hexaboride nanoparticles cooperate to achieve controlled release of MXD, effectively reduce the side effects of the drug, 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.

Description

Technical Field

[0001] The present 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 androgenic alopecia (AGA), a chronic, progressive disease caused by high levels of testosterone, an androgen. While AGA is not a serious, life-threatening condition, the physical and aesthetic changes caused by hair loss can significantly impact patients' psychological well-being and quality of life, making the development of effective AGA treatment strategies highly desirable.

[0003] Currently, the only two US Food and Drug Administration (FDA)-approved treatments for AGA are oral finasteride and topical minoxidil (MXD), both of which require daily administration for over 6 months. Because oral finasteride often causes systemic toxicity, most patients prefer MXD formulations for hair regrowth. However, these topical MXD solutions or foams often suffer from poor patient compliance and limited therapeutic efficacy due to frequent dosing (i.e., ∼180 doses) and low bioabsorption (i.e., <1%), which is attributed to the skin's physical barrier, the stratum corneum. Among various approaches to increase skin penetration and enhance therapeutic efficacy, the use of microneedles (MNs) has garnered considerable attention due to their unique properties. Microneedles (MNs) can effectively penetrate the stratum corneum for transdermal drug delivery, improving drug delivery efficiency and enabling self-administration without generating any biohazardous waste. Among these, hydrogel-forming microneedles (HFMs) are composed of swellable polymers (cross-linked hydrogels). These microneedles can achieve sustained drug delivery over extended periods of time by either incorporating the drug into the polymer structure during fabrication or by loading the drug 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 in the prior art that the release rate and pattern of the drug by the hydrogel microneedle are difficult to control.

[0006] In a 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 PLGA-minoxidil microneedles with near-infrared response, comprising the following steps:

[0008] Providing PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles and a first polyvinyl alcohol aqueous solution;

[0009] 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.

[0010] Compared with the prior art, the present invention has the following beneficial effects:

[0011] The present invention combines PLGA-minoxidil microspheres with hydrogel microneedles with near-infrared response. On a microscopic level, the microporous structure of the microspheres and the near-infrared response of lanthanum hexaboride nanoparticles cooperate to achieve controlled release of MXD, effectively reduce drug side effects, better maintain drug concentration in the body, and achieve better therapeutic effects. On a macroscopic level, 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

[0012] Figure 1 This is a schematic structural diagram of an embodiment of the PLGA-minoxidil microneedle with near-infrared response provided by the present invention;

[0013] Figure 2 This is a scanning electron micrograph of PLGA-minoxidil microspheres prepared with a molar ratio of lactic acid to glycolic acid of 50:50 in the present invention;

[0014] Figure 3 This is a scanning electron micrograph of PLGA-minoxidil microspheres prepared with a molar ratio of lactic acid to glycolic acid of 75:25 in the present invention;

[0015] Figure 4 A photo of the PVA hydrogel microneedles prepared with a mass ratio of PVA (type 1788) to PVA (type 1799) of 6:4 and a micrograph of the needle tip;

[0016] Figure 5 A photo of the PVA hydrogel microneedles prepared with a mass ratio of PVA (type 1788) to PVA (type 1799) of 7:3 and a micrograph of the needle tip;

[0017] Figure 6 This is an image of the melting of the PLGA-minoxidil microneedles with near-infrared response prepared in Example 1 of the present invention after being irradiated with near-infrared light for 10 seconds;

[0018] Figure 7 This is an image of the melting of the PLGA-minoxidil microneedles with near-infrared response prepared in Comparative Example 1 of the present invention after being irradiated with near-infrared light for 10 seconds;

[0019] Figure 8 This is an image of the melting of the PLGA-minoxidil microneedles with near-infrared response prepared in Comparative Example 2 of the present invention after being irradiated with near-infrared light for 10 seconds;

[0020] Figure 9 These are images of the cumulative drug release of the near-infrared-responsive PLGA-minoxidil microneedles prepared in Example 1 of the present invention under near-infrared light irradiation and without near-infrared light irradiation. DETAILED DESCRIPTION

[0021] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention will be further described in detail below with reference to 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.

[0022] 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.

[0023] Lanthanum hexaboride (Lanthanum hexaboride) has a CsCl crystal structure, belonging to the simple cubic system. It is a rare earth boride with the molecular formula LaB6. LaB6 possesses many superior properties, such as electron emission intensity, radiation resistance, and high-temperature chemical stability, making it widely used in numerous high-tech fields. Leveraging the absorption and scattering properties of nanoscale LaB6 in the near-infrared band, it possesses near-infrared absorption properties and can be used in sensors, microelectronics, and optical thin films. Compared with other photothermal materials, LaB6 has high photothermal conversion efficiency and low cost. After absorbing near-infrared light, its temperature remains around 50°C, matching the melting point of PVA hydrogel microneedles and preventing thermal damage to the skin.

[0024] The present invention uses minoxidil as a drug for treating androgenic alopecia, and utilizes PLGA loaded with MXD to form microspheres, which are then combined with near-infrared light-responsive microneedles to achieve sustained and controlled release of MXD, thereby improving bioavailability and reducing MXD's side effects. The PVA hydrogel used to make the needle body is a combination of low-saponified PVA and highly saponified PVA, effectively overcoming the shortcomings of using only PVA as a needle body material, thereby penetrating the skin's stratum corneum and opening a drug delivery channel. Compared to traditional drug delivery methods, this microneedle system enables targeted delivery while reducing skin irritation, achieving better therapeutic effects and improving patients' mental health and quality of life.

[0025] In this embodiment, the average particle size of the PLGA-minoxidil microspheres is 8-12 μm.

[0026] In this embodiment, the average particle size of the lanthanum hexaboride nanoparticles is 20-50 nm.

[0027] In this embodiment, the mass ratio of PVA 1788 to PVA 1799 is (1.2-1.8):1, further preferably 1.5:1. A single low-saponification PVA hydrogel can result in insufficient mechanical strength of the needle body, while a single high-saponification PVA hydrogel can make the needle body difficult to mold. The present invention combines the advantages of both by compounding two PVAs with different saponification degrees in the aforementioned ratio, resulting in microneedles with both the mechanical strength to penetrate human skin and the ease of molding. Furthermore, the melting point of the microneedles is within the temperature range of the heat emitted by the near-infrared material upon absorption of near-infrared light.

[0028] In a second aspect, the present invention provides a method for preparing PLGA-minoxidil microneedles with near-infrared response, comprising the following steps:

[0029] S1, providing PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles and a first polyvinyl alcohol aqueous solution;

[0030] 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.

[0031] In this embodiment, in step S1, the preparation steps of PLGA-minoxidil microspheres include:

[0032] S11, preparing a second polyvinyl alcohol aqueous solution;

[0033] S12, preparing a minoxidil glacial acetic acid solution and a poly(lactic acid-co-glycolic acid) (PLGA) ethyl acetate (EA) solution, and uniformly mixing the minoxidil glacial acetic acid solution, the poly(lactic acid-co-glycolic acid) ethyl acetate solution, and chloroform to obtain an organic phase;

[0034] S13, uniformly mixing the second polyvinyl alcohol aqueous solution and the organic phase to form an O / W emulsion, followed by stirring, a second centrifugation, washing, and drying to obtain PLGA-minoxidil microspheres.

[0035] 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%.

[0036] Wherein, in step S11, during the process of preparing the second polyvinyl alcohol aqueous solution, the dissolution temperature is 80-100°C.

[0037] 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.

[0038] In step S12, during the preparation of the minoxidil glacial acetic acid solution, the dissolution temperature is -10-0°C, and the dissolution time is 30-60 minutes.

[0039] Wherein, in step S12, the concentration of PLGA in the ethyl acetate solution of poly(lactic-co-glycolic acid) is 2-5 mg / uL, further 3.6 mg / uL.

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] Furthermore, the speed of the homogenizer is 5000-8000 rpm, further 6000 rpm, and the homogenization time is 120-300 s, further 180 s.

[0045] 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.

[0046] 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.

[0047] Wherein, in step S13, the washing method is deionized water washing.

[0048] Wherein, in step S13, the drying method is freeze-drying.

[0049] In this embodiment, in step S1, the mass fraction of the first polyvinyl alcohol aqueous solution is 8%-12%, and further 10%.

[0050] In this embodiment, in step S1, during the preparation of the first polyvinyl alcohol aqueous solution, the dissolution temperature is 80-100°C.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] In this embodiment, the drying temperature is 30-40° C., and the drying time is 1-3 hours.

[0055] Screening test 1 Screening of the molar ratio of lactic acid to glycolic acid

[0056] Screening test 1-1

[0057] 2g of PVA (type 1788) solid powder was dissolved in 8ml of pure water at 100°C. After complete dissolution, the mixture was allowed to cool to room temperature. 300mg of MXD was dissolved in 400µL of glacial acetic acid. 360mg of PLGA (lactic acid:glycolic acid molar ratio, 50:50) was dissolved in 100µL of ethyl acetate (EA). The mixture was then mixed with 1.9mL of trichloromethane (TCM) and a minoxidil solution in glacial acetic acid to form an organic phase. The organic phase was mixed with the resulting 20% ​​PVA aqueous solution and then homogenized at 6000rpm for 180s to form an O / W emulsion. The emulsion was stirred at room temperature for 7-8 hours to evaporate the organic solvent. The microspheres were collected by centrifugation at 4200rpm for 15 minutes, washed four times with deionized water, and lyophilized. The resulting white powder was stored in the refrigerator until use.

[0058] Screening test 1-2

[0059] Compared with the screening test 1-1, the only difference is that the molar ratio of lactic acid:glycolic acid is 75:25.

[0060] See also Figure 2 and 3 ,pass Figure 2 and 3 It can be seen that the morphology of microspheres prepared with different molar ratios of lactic acid to glycolic acid in PLGA varies. Microspheres prepared with a 75:25 molar ratio exhibited partial defects, while microspheres prepared with a 50:50 molar ratio exhibited smooth surfaces and regular shapes. This may be due to the lower intrinsic viscosity and better hydrophilicity of PLGA at a 50:50 ratio. Therefore, the optimal molar ratio of lactic acid to glycolic acid in PLGA-minoxidil microspheres is 50:50.

[0061] Screening test 2 Screening of the mass ratio of PVA (type 1788) to PVA (type 1799)

[0062] Screening test 2-1

[0063] Mix 0.6g of PVA (1788) and 0.4g of PVA (1799) and pour into a beaker containing 9ml of pure water. Heat in an oil bath to 100°C for 30 minutes. Once completely dissolved, cool to room temperature to obtain a composite PVA aqueous solution. This composite PVA aqueous solution is then poured into a mold and centrifuged at 4200 rpm for 5 minutes. The sample is removed and stored in a 30°C oven for 2 hours to obtain a thin-film MN patch.

[0064] Screening test 2-2

[0065] Compared with the screening test 2-1, the only difference is that 0.7 g of PVA (type 1788) and 0.3 g of PVA (type 1799) were mixed.

[0066] See also Figure 4-5 ,pass Figure 4-5 It can be seen that microneedles made with a PVA (1788):PVA (1799) ratio of 7:3 have low mechanical strength and exhibit bending, while microneedles made with a PVA (1788):PVA (1799) ratio of 6:4 have very good mechanical strength. This suggests that the optimal mass ratio of low-saponification to high-saponification PVA hydrogel is 6:4.

[0067] Example 1

[0068] Preparation of PLGA-minoxidil microneedles with near-infrared response

[0069] Mix 500 mg of PLGA-minoxidil microspheres obtained in Screening Experiment 1-1 and 50 mg of lanthanum hexaboride nanoparticles in 10 ml of the composite PVA aqueous solution obtained in Screening Experiment 2-1. Pour the mixture into a mold and centrifuge at 4200 rpm for 5 minutes. Remove the sample and store it in a 30°C oven for 2 hours to obtain a thin-film MN patch.

[0070] Comparative Example 1

[0071] Compared with Example 1, the only difference is that the added amount of lanthanum hexaboride nanoparticles is 20 mg.

[0072] Comparative Example 2

[0073] Compared with Example 1, the only difference is that the added amount of lanthanum hexaboride nanoparticles is 80 mg.

[0074] Performance Testing

[0075] 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 and irradiated with 808nm near-infrared light. The samples were then analyzed using a UV-visible spectrophotometer to establish a drug release (%)-time (h) curve of MXD-MPs-MN to verify the drug release of the microneedles with and without near-infrared light irradiation.

[0076] See also Figure 6-8 ,pass Figure 6-8 It can be seen that the microneedles prepared by adding 50 mg of lanthanum hexaboride nanoparticles to 10 ml of composite PVA aqueous solution have a slightly melted tip after 10 seconds of near-infrared light irradiation, indicating that the near-infrared response is good and can play a sustained release role ( Figure 6 When 20 mg of lanthanum hexaboride nanoparticles were added to 10 ml of composite PVA aqueous solution, the microneedles were 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 microneedles were 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.

[0077] See also Figure 9 ,pass Figure 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 under conditions without near-infrared light irradiation, 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 controlled release of MXD and improve drug delivery efficiency.

[0078] Compared with the prior art, the present invention has the following beneficial effects:

[0079] (1) The microneedles of the present invention can penetrate the stratum corneum of the skin to deliver drugs, thereby improving drug delivery efficiency. The PLGA microspheres can both load MXD and reduce its side effects.

[0080] (2) The microneedle of the present invention introduces a near-infrared response system, the photocatalyst of which is LaB6 (20-50 nm). 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.

[0081] (3) The wavelength of 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 area, the near-infrared light used for treatment needs to be easily accessible and portable. This wavelength is the wavelength of the most readily available near-infrared light source (near-infrared flashlight) on the market. Therefore, the PLGA-minoxidil microneedles of the present invention with near-infrared response have high practical value.

[0082] The specific embodiments of the present invention described above do not limit the scope of protection 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 scope of protection 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 materials of the base and the needle body are a combination of PVA 1788 and PVA 1799, and the mass ratio of the PVA 1788 to the PVA 1799 is (1.2-1.8): 1; The PLGA-minoxidil microneedles with near-infrared response are prepared by the following steps: providing PLGA-minoxidil microspheres, lanthanum hexaboride nanoparticles and a first polyvinyl alcohol aqueous solution; uniformly mixing the PLGA-minoxidil microspheres, the lanthanum hexaboride nanoparticles and the first polyvinyl alcohol aqueous solution and pouring the mixture into a microneedle mold, followed by a first centrifugation and drying to obtain the PLGA-minoxidil microneedles with near-infrared response; the first polyvinyl alcohol aqueous solution is obtained by dissolving PVA 1788 and PVA 1799 in water; 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.

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. A method for preparing the PLGA-minoxidil microneedle with near-infrared response according to any one of claims 1 to 2, 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 a 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; The usage ratio of the first polyvinyl alcohol aqueous solution to the lanthanum hexaboride nanoparticles is 1 ml: (4-6) mg; the usage ratio of the first polyvinyl alcohol aqueous solution to the PLGA-minoxidil microspheres is 1 ml: (40-60) mg.

4. The method for preparing the PLGA-minoxidil microneedle with near-infrared response according to claim 3, characterized in that: The preparation steps of the PLGA-minoxidil microspheres include: preparing a second polyvinyl alcohol aqueous solution; preparing a minoxidil glacial acetic acid solution and a polylactic acid-co-glycolic acid (PLGA) ethyl acetate 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; The second polyvinyl alcohol aqueous solution and the organic phase are uniformly mixed to form an O / W emulsion, which is then stirred, centrifuged a second time, washed, and dried to obtain PLGA-minoxidil microspheres.

5. The method for preparing PLGA-minoxidil microneedles with near-infrared response according to claim 4, 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%; The minoxidil solution in glacial acetic acid has a minoxidil concentration of 0.5-1 mg / uL; In the poly(lactic-co-glycolic acid) ethyl acetate solution, the concentration of PLGA 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).

6. The method for preparing PLGA-minoxidil microneedles with near-infrared response according to claim 4, 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; The second polyvinyl alcohol aqueous solution and the organic phase are mixed uniformly using a homogenizer 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.

7. The method for preparing the PLGA-minoxidil microneedle with near-infrared response according to claim 3, characterized in that: The mass fraction of the first polyvinyl alcohol aqueous solution is 8%-12%.

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

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