Application of artemisia nanovesicles in preparation of drugs for treating androgenetic alopecia

Abstract

The application discloses application of artemisia annua nano vesicles in preparation of a medicine for treating androgenetic alopecia. Nano vesicles are obtained by differential centrifugation from artemisia annua, the nano vesicles are loaded in methylacrylated gelatin hydrogel, and a soluble microneedle array is prepared by using a microtemplate method and a UV crosslinking method. Animal experiment results show that the microneedle patch can efficiently penetrate the skin barrier, deliver the nano vesicles to the perifollicular region and realize slow release, effectively reverse the miniaturization process of the hair follicles of androgenetic alopecia model mice, and promote hair regeneration. The application provides a safe, efficient and minimally invasive new treatment strategy for androgenetic alopecia, and has a wide clinical application prospect.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and more specifically, to the application of artemisinin nanovesicles in the preparation of drugs for treating androgenetic alopecia. Background Technology

[0002] Androgenetic alopecia (AGA) is one of the most common types of progressive hair loss in clinical practice, characterized by high incidence, prolonged course, and gradual worsening. It can significantly affect patients' appearance, self-perception, social function, and overall quality of life. Current research and treatment guidelines clearly indicate that the core pathological basis of AGA includes androgen-dependent follicular miniaturization, abnormal follicular cycle (shortened anagen phase, premature catagen phase), and changes in the local microenvironment of the hair follicle, ultimately manifesting as the gradual transformation of terminal hair into vellus hair and a progressive decrease in hair density. In addition to genetic and androgen factors, perifollicular inflammatory infiltration, oxidative stress, and fibrotic remodeling are also considered important contributing factors to the continued progression of AGA. Among the aforementioned microenvironmental abnormalities, the transforming growth factor-β (TGF-β) signaling pathway plays a particularly crucial role. Multiple studies have shown that TGF-β can induce the initiation of the hair follicle regression phase, promote apoptosis of hair follicle epithelial cells, and participate in perifollicular fibrotic remodeling, and is significantly upregulated in hair follicles in the hair loss areas of AGA patients. Therefore, targeted intervention against abnormal TGF-β activation and its downstream pathways has a clear pathophysiological basis.

[0003] Currently, standard treatment for androgenetic alopecia (AGA) mainly includes topical minoxidil and oral finasteride, both of which are listed as core basic treatment regimens in domestic and international guidelines. The Chinese Guidelines for the Diagnosis and Treatment of Androgenetic Alopecia (2023 Edition) also explicitly recommend them. However, existing regimens still have significant limitations in clinical practice: ① Finasteride usually requires several months of continuous treatment to observe a clear therapeutic effect, and hair loss often continues to progress after discontinuation. Furthermore, some patients have concerns about its potential sexual function-related adverse reactions. ② Although minoxidil is widely used, its hair growth-promoting mechanism is not fully understood. It requires long-term topical application, has a relatively slow onset of action, and some patients experience local irritation or poor compliance. Overall, existing regimens still face challenges such as significant individual differences in efficacy, difficulty in long-term maintenance, and limitations in their mechanisms of action. Clinically, there is an urgent need to explore intervention strategies that combine novel mechanisms of action with promising topical application prospects.

[0004] Plant-derived extracellular vesicles (PEVs) are nanoscale membrane vesicles actively secreted by plant cells. These vesicles range in diameter from 30 to 500 nanometers, possess a lipid bilayer structure, and contain active ingredients such as proteins, nucleic acids, and plant-specific metabolites. They are secreted through exosomes, microvesicles, and apoptotic bodies, and are widely distributed in plant tissues and secretions, including roots, stems, and leaves. PEVs have been applied in fields such as medicine and health (e.g., drug delivery, adjuvant therapy), functional foods (natural preservation and active ingredient addition), cosmetics (delivery of active ingredients and skin care), and agriculture (stress regulation, growth promotion), providing new possibilities for research and applications in these areas. Different plant PEVs exhibit functional differentiation due to the unique bioactive molecules they carry. The core of this differentiation lies in the specificity of their contents (e.g., differences in miRNAs, metabolites, and membrane proteins). Therefore, PEVs from different sources exhibit unique therapeutic potential due to the specific bioactive molecules they carry. For example, broccoli-derived PEVs have shown effects in regulating gut microbiota and improving metabolic syndrome in studies; green tea-derived PEVs can be used as natural preservatives to extend the shelf life of strawberries. In addition, spirulina-derived PEVs have been explored for osteoarthritis, purple-backed amaranth-derived PEVs for skin repair, and alfalfa-derived PEVs for improving the drought resistance of wheat.

[0005] Artemisia annua nanovesicles are natural nanoscale vesicles extracted from the fresh aerial parts of Artemisia annua L., a plant belonging to the genus Artemisia in the family Asteraceae. These vesicles possess the dual properties of a novel drug carrier and an active ingredient, and due to their excellent biocompatibility and extremely low cytotoxicity, they show broad application prospects in the biomedical field (such as drug delivery, anti-inflammatory and anti-tumor therapy). For example, Chinese patent application CN121891285A discloses its use for skin moisturizing, barrier repair, and soothing; Wang et al. disclosed that artemisia-derived extracellular vesicles inhibit breast cancer growth without systemic toxicity by regulating the NF-κB / PPARγ pathway (Wang, Y., Meng, L., Su, S. et al. Artemisia annua-derived extracellular vesicles reprogram breast tumor immune microenvironment via altering macrophage polarization and synergizing recruitment of Tlymphocytes. Chin Med 20, 149 (2025). https: / / doi.org / 10.1186 / s13020-025-01210-1); Ye L et al. disclosed artemisia-derived nanovesicles for the treatment of acute lung injury and viral pneumonia (Ye L, Gao Y, Mok SWF, Liao W, Wang Y, Chen C, Yang L, Zhang J, Shi L. Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derivednanoves to mitigate acute lung injury and viral pneumonia. JNanobiotechnology. 2024 Apr 18;22(1):190. doi: 10.1186 / s12951-024-02473-w.). However, there are currently no reports on the role of artemisinin nanovesicles in AGA. Summary of the Invention

[0006] The purpose of this invention is to overcome the above-mentioned defects and deficiencies in the prior art and to provide the application of artemisinin nanovesicles in the preparation of drugs for treating androgenetic alopecia.

[0007] The above-mentioned objective of the present invention is achieved through the following technical solution: This invention demonstrates that artemisinin nanovesicles significantly promote the proliferation of human dermal papilla cells (HHDPCs) and exert a protective effect against dihydrotestosterone (DHT)-induced microenvironmental damage. They significantly inhibit DHT-induced abnormal TGF-β expression in HHDPCs, improve DHT-induced cell viability decline, promote cell proliferation, reduce ROS levels, and improve mitochondrial membrane potential decline, suggesting a clear cytoprotective effect. Considering that AGA lesions are mainly located in the scalp hair follicles and surrounding microenvironment, and that traditional topical preparations are limited by the skin barrier, resulting in limited local delivery efficiency, this invention further employs a microneedle delivery strategy to improve the penetration and accumulation of artemisinin active extracts in the scalp, especially in the hair follicle region. Animal experiments show that artemisinin active extract microneedles significantly improve the hair loss pattern in AGA model mice, promote hair regeneration, increase the number of hair follicles in the anagen phase, improve hair follicle miniaturization, and reduce elevated serum testosterone and DHT levels, without significant in vivo toxicity. The above results indicate that artemisinin nanovesicles can delay hair follicle miniaturization and promote hair growth by inhibiting TGF-β-related abnormal signaling, alleviating oxidative stress, improving mitochondrial function, and enhancing local effective delivery, and can be used for the effective treatment of AGA.

[0008] Therefore, the present invention first provides the application of artemisinin nanovesicles in the preparation of drugs for treating androgenetic alopecia.

[0009] Preferably, the drug is a transdermal administration formulation.

[0010] This invention also provides the application of soluble microneedles loaded with artemisinin nanovesicles in the preparation of drugs for treating androgenetic alopecia.

[0011] Specifically, the drug exerts its therapeutic effect by promoting hair regeneration, increasing the number of hair follicles in the growth phase, and improving hair follicle miniaturization.

[0012] Furthermore, the artemisia nanovesicles have a particle size of 160–165 nm and a zeta potential of -18 to -20 mV.

[0013] Furthermore, the artemisia nanovesicles were prepared using differential centrifugation.

[0014] Preferably, the differential centrifugation method includes the following steps: washing and chopping fresh Artemisia annua whole herb, adding water and mixing, crushing, making a homogenate and filtering, separating by gradient centrifugation, resuspending, and extruding through a 0.20-0.25μm (preferably 0.22μm) filter membrane to obtain the product; the gradient centrifugation is performed sequentially at 3000-5000rpm for 25-35min (preferably 4000rpm for 30min), 11000-13000rpm for 25-35min (preferably 12000rpm for 30min), and 30000-50000g for 55-65min (preferably 40000g for 60min), and the supernatant is centrifuged at 140000-160000g for 85-95min (preferably 150000g for 90min), and the supernatant is discarded.

[0015] Furthermore, the mass ratio of artemisia annua to water is 1:4 to 6.

[0016] This invention uses Artemisia annua as the extraction target. After pretreatment, Artemisia annua is first centrifuged at low speed to remove impurities, and then centrifuged at high speed to separate exosomes (i.e., gradient centrifugation). Then, it is filtered through a membrane and squeezed. By controlling the speed, time and pore size of the gradient centrifugation membrane, Artemisia annua nanovesicles can be prepared.

[0017] Furthermore, the soluble microneedles are soluble microneedles made from methacrylamide gelatin (GelMA).

[0018] Preferably, the method for preparing the methacrylamide gelatin soluble microneedles loaded with artemisia annua nanovesicles is as follows: mixing the suspension of artemisia annua nanovesicles with a methacrylamide gelatin solution, adding a photoinitiator, and mixing thoroughly to obtain a methacrylamide gelatin prepolymer solution loaded with nanovesicles; injecting the prepolymer solution into a microneedle mold and performing photocuring crosslinking to obtain the microneedles.

[0019] Preferably, the photoinitiator is 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone.

[0020] Preferably, the mass ratio of the artemisia nanovesicles to methacrylamide gelatin is 1:100~300 (preferably 1:200).

[0021] Preferably, the preparation method of GelMA includes the following steps: dissolving gelatin in phosphate buffer, heating to 50-60°C and stirring until completely dissolved to prepare a gelatin solution of a certain concentration (e.g., 5%-15% w / v). Adding methacrylic anhydride dropwise to the gelatin solution, stirring and reacting at 50-60°C for 1-3 hours, causing the amino groups on the gelatin molecular chain to undergo an amidation reaction with the methacrylic anhydride, yielding methacrylated gelatin. Transferring the reaction solution to a dialysis bag and dialyzing with deionized water or phosphate buffer for one week to remove unreacted methacrylic anhydride and other small molecule impurities. Freeze-drying the dialyzed GelMA solution to obtain GelMA powder, which is stored at -20°C for later use.

[0022] The prepared methacrylamide gelatin (GelMA) matrix material exhibited good safety and no significant cytotoxicity to human dermal papilla cells. The GelMA-loaded nanovesicles provided by this microneedle demonstrated reliable overall safety. In mice with androgenetic alopecia (AGA), this microneedle system significantly promoted hair growth and effectively reversed hair follicle miniaturization through a dual anti-inflammatory and antioxidant mechanism, achieving ideal hair regeneration. Furthermore, the GelMA-loaded microneedles exhibit: 1) Highly efficient transdermal delivery: Using GelMA-loaded microneedles as a delivery carrier, the skin barrier is breached through physical puncture, efficiently delivering nanovesicles to the target tissue surrounding the hair follicle, solving the problem of low transdermal absorption rates in traditional topical formulations. 2) Sustained-release and long-lasting effect: Utilizing the biodegradable properties of GelMA hydrogel, the nanovesicles are slowly released intradermally, prolonging the duration of drug action, reducing dosing frequency, and improving patient compliance.

[0023] Compared with the prior art, the present invention has the following beneficial effects: This invention provides the application of artemisinin nanovesicles in the preparation of drugs for treating androgenetic alopecia. This invention is the first to use artemisinin nanovesicles in the treatment of androgenetic alopecia. Artemisinin nanovesicles can effectively inhibit the abnormal activation of the TGF-β signaling pathway in the hair follicle microenvironment and achieve multi-target therapy with anti-inflammatory, antioxidant, and angiogenesis-promoting functions. This overcomes the problem that existing single-mechanism drugs cannot simultaneously address multiple pathological factors in the hair follicle microenvironment, such as oxidative stress, inflammatory response, and insufficient vascular supply. Ultimately, it works by promoting hair regeneration, increasing the number of hair follicles in the growth phase, and improving hair follicle miniaturization, thereby fundamentally blocking the pathological process of hair follicle miniaturization, rather than merely improving symptoms. This invention provides a safe, efficient, and minimally invasive new treatment strategy for androgenetic alopecia, with broad clinical application prospects. Attached Figure Description

[0024] Figure 1 The figure shows the characterization results of artemisinin nanovesicles.

[0025] Figure 2 The figure shows the effect of artemisia annua nanovesicles on DHT-induced damage in HHDPC.

[0026] Figure 3 This image shows the in vitro therapeutic effect of artemisinin nanovesicles.

[0027] Figure 4 The figure shows the characterization results of GelMA soluble microneedles loaded with artemisinin nanovesicles.

[0028] Figure 5 The in vivo pharmacodynamic results of GelMA soluble microneedles loaded with artemisinin nanovesicles are shown in the figure. Detailed Implementation

[0029] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0030] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0031] Example 1: Preparation and characterization of artemisinin nanovesicles After washing and chopping fresh Artemisia annua, it was added to a high-speed blender at a mass ratio of Artemisia annua to water of 1:5. After being crushed into a homogenate, it was filtered and separated by gradient centrifugation, i.e., 4000rpm×30min, 12000rpm×30min, 40000g×60min. The supernatant was collected at 150000g×90min, the supernatant was discarded, and the mixture was resuspended in PBS and extruded through a 0.22-micron filter membrane to obtain Artemisia annua nanovesicles (Art-PEVs).

[0032] The particle size and potential of artemisinin nanovesicles were determined. Figure 1 In the figure, A represents the particle size and C represents the Zeta potential. The results show that the particle size is around 163.8 nm and the Zeta potential is -19.85 mV, proving that it has the characteristics of uniform and stable particle size. The morphology of the exosomes was observed by transmission electron microscopy. Figure 1 Image B shows the morphology of exosomes observed by transmission electron microscopy, revealing that the artemisia-derived nanovesicles are uniformly spherical structures.

[0033] Example 2: Artemisia annua nanovesicles promote the proliferation of DHT-induced damaged HHDPCs HHDPC cells (Human Hair Dermal Papilla Cells) were treated with different concentrations (0, 1, 2, 5, 10, 20, 40, 60, 80, 100 μg / mL) of Art-PEVs for 48 h, and the effect of Art-PEVs on HHDPC cell viability was detected by CCK-8 assay. Figure 2 Figure A shows the effect of Art-PEVs on HHDPC cell viability, indicating no significant toxicity within this concentration range. Further, under 5 nmol / L dihydrotestosterone (DHT) induction conditions, HHDPCs were treated with different concentrations (1, 2, 5, 10, 20, 40, 80, 100 μg / mL) of Art-PEVs for 48 h. Figure 2 Figure B shows the effect of Art-PEVs on the viability of DHT-induced damaged HHDPC cells. The results indicate that Art-PEVs significantly alleviated the inhibition of HHDPC activity by DHT, with the most significant protective effects observed at 20 μg / mL (Art-PEVs-L) and 40 μg / mL (Art-PEVs-H). Further crystal violet staining was performed... Figure 2 The middle C represents the crystal violet staining result, further confirming that Art-PEVs can significantly improve DHT-induced HHDPC damage and promote cell proliferation.

[0034] Example 3: In vitro therapeutic effects of artemisinin nanovesicles Furthermore, in the 5 nmol / L DHT-induced HHDPC cell model constructed in Example 2, the expression of TGF-β and androgen receptor (AR) in HHDPC cells was detected by Western blot and RT-qPCR. Figure 3 Image A shows Western blot results, and image B shows RT-qPCR results. Both Western blot and RT-qPCR results showed that Art-PEVs significantly ameliorated DHT-induced abnormal expression of TGF-β and AR. Further analysis using flow cytometry combined with the DCFH-DA fluorescent probe revealed… Figure 3 In the middle, C represents the results of flow cytometry, and D represents the results of DCFH-DA fluorescent probe detection. It was found that Art-PEVs significantly reduced the DHT-induced increase in ROS levels in both HHDPC and RAW264.7 cells, suggesting that they have a role in mitigating oxidative stress damage. Furthermore, JC-1 assays were performed... Figure 3 E represents the JC-1 assay results, showing that Art-PEVs can significantly alleviate the DHT-induced decrease in mitochondrial membrane potential in HHDPCs, suggesting that they can improve mitochondrial function.

[0035] Example 4: Preparation and characterization of GelMA-soluble microneedles loaded with artemisinin nanovesicles The suspension of Artemisia annua nanovesicles prepared in Example 1 was mixed with GelMA solution in a certain proportion, and a photoinitiator (2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone, Irgacure 2959) was added and mixed thoroughly to obtain a GelMA prepolymer solution loaded with nanovesicles. The concentration of the Artemisia annua nanovesicle suspension was 10 mg / mL. 500 μL of vesicle suspension was mixed with 1 mL of photoinitiator (5 mg / mL) + 1 g of GelMA matrix, and finally 3.5 mL of PBS solution to obtain a 5 mL GelMA prepolymer solution, with a final GelMA concentration of 0.2 g / mL. The prepolymer solution was injected into a microneedle mold having a grooved structure of microneedle arrays. The mold was degassed under vacuum to ensure the prepolymer solution fully filled the microneedle cavities of the mold. The filled mold was placed under a UV lamp (wavelength 365 nm, intensity 5~20 mW / cm²) for 1~5 minutes to allow GelMA to cross-link and solidify, forming a microneedle structure with a certain mechanical strength. After drying the moisture in an oven, the cross-linked and solidified microneedles were carefully peeled off from the mold to obtain an artemisinin nanovesicle-loaded GelMA soluble microneedle patch.

[0036] The prepared microneedle array was observed using a stereomicroscope. Figure 4 Figures A through B show the observation results of GelMA-soluble microneedles under bright-field mode. Bright-field mode revealed that the prepared GelMA-soluble microneedles loaded with artemisinin-derived nanovesicles exhibited 8... The microneedle array structure of 8, with the needle tip structure shown under high magnification; Figure 4 Figures C-D show the observation results of GelMA soluble microneedles loaded with Artemisia annua nanovesicles after Rhodamine B staining in fluorescence mode. In fluorescence mode, the tips of the GelMA soluble microneedles loaded with Artemisia annua nanovesicles after Rhodamine B staining exhibit red fluorescence.

[0037] Example 5: In vivo pharmacodynamic study of GelMA-soluble microneedles loaded with artemisinin nanovesicles The GelMA-soluble microparticles loaded with artemisinin nanovesicles prepared in Example 4 were used to intervene in an AGA model established by subcutaneous injection of 10 mg / (kg·d) testosterone propionate solution in C57BL / 6 mice. Specifically, the mice were grouped as follows: ①NC group: Daily subcutaneous injection of equal volume of normal saline; ②AGA model group: 10 mg / (kg•d) testosterone propionate solution was injected subcutaneously daily; ③ Blank MN group: 10 mg / (kg•d) testosterone propionate solution was injected subcutaneously daily, plus blank microneedling every 2 days; ④Art-PEVs MN group: Daily subcutaneous injection of 10 mg / (kg•d) testosterone propionate solution + microneedles loaded with artemisinin nanovesicles every 2 days; ⑤ Minoxidil group: 10 mg / (kg•d) testosterone propionate solution was injected subcutaneously daily + 500 μL of 5% minoxidil was applied to the back daily; One microneedle is administered each time.

[0038] Observe the mice, Figure 5 Figure A shows the observation results of AGA model mice after intervention in different treatment groups. The results showed that Art-PEVs MN could significantly improve the hair loss phenotype of model mice and promote hair regeneration. Continuous observation of dorsal hair growth revealed that, compared with the normal control group (NC), the dorsal skin of AGA model mice remained bald for 25 days, with no obvious hair regeneration. The Blank MN microneedle group and the minoxidil positive control group only showed mild hair improvement, with sparse hair coverage and slow growth. In contrast, the Art-PEVs MN group showed scattered hair growth from day 14, forming a more obvious hair coverage area by day 25. Although the hair density and uniformity were still lower than the NC group, they were significantly better than the AGA model group, Blank MN group, and minoxidil positive control group, suggesting that Artemisia annua extract microneedles can effectively promote hair regeneration and improve the AGA phenotype.

[0039] Perform H&E staining on skin tissue. Figure 5 Image B shows the H&E staining results of skin tissue from AGA model mice after intervention in different treatment groups, further confirming significant differences in hair follicle morphology and number among the groups. Compared with the NC group, the AGA model group showed a significant reduction in the number of hair follicles, atrophy of follicle volume, disordered structure, an increased proportion of resting follicles, and a decrease in dermal papilla cells, indicating successful modeling and induction of hair follicle miniaturization and hair cycle arrest. The Blank MN group showed a slight increase in the number of hair follicles, but the overall structure remained small, with most in the early anagen phase, suggesting that simple microneedle stimulation had limited effect. The minoxidil group showed similar hair follicle morphology to the Blank MN group, with no significant increase in functional anagen follicles. In contrast, the Art-PEVs MN group showed more hair follicles in the anagen phase, with more intact follicle structure, melanin deposition within the hair shaft, and relatively abundant dermal papilla cells, indicating that it can promote the transformation of hair follicles from the resting phase to the anagen phase and reverse hair follicle miniaturization.

[0040] Further testing of serum testosterone and dihydrotestosterone levels was conducted. Figure 5 D represents the serum testosterone and dihydrotestosterone levels in AGA model mice after intervention in different treatment groups. It was found that Art-PEVs MN intervention could reduce the elevated serum testosterone and dihydrotestosterone levels after modeling, while no significant improvement was observed in the Blank MN group.

[0041] Further safety evaluation should be conducted. Figure 5 In the middle (C), the results of H&E staining of the heart, liver, spleen, lung, kidney, and skin tissues of AGA model mice after Art-PEV intervention are shown. The results indicate that after 25 days of continuous intervention, no obvious abnormal pathological changes were observed in the H&E staining of the heart, liver, spleen, lung, kidney, and skin tissues of mice, suggesting that Artemisia annua nanovesicle microneedles have good in vivo safety.

Claims

1. Application of Artemisia annua nanovesicles in the preparation of drugs for treating androgenetic alopecia.

2. Application of soluble microneedles loaded with artemisinin nanovesicles in the preparation of drugs for treating androgenetic alopecia.

3. The application according to claim 1 or 2, characterized in that, The drug exerts its therapeutic effect by promoting hair regeneration, increasing the number of hair follicles in the growth phase, and improving hair follicle miniaturization.

4. The application according to claim 1 or 2, characterized in that, The artemisia nanovesicles were prepared by differential centrifugation.

5. The application according to claim 4, characterized in that, The differential centrifugation method includes the following steps: washing and chopping fresh Artemisia annua whole herb, adding water and mixing, crushing, making a homogenate and filtering, separating by gradient centrifugation, resuspending, and extruding through a 0.20-0.25μm filter membrane to obtain the product; the gradient centrifugation is performed sequentially at 3000-5000rpm for 25-35min, 11000-13000rpm for 25-35min, and 30000-50000g for 55-65min, and the supernatant is centrifuged at 140000-160000g for 85-95min, and the supernatant is discarded.

6. The application according to claim 2, characterized in that, The soluble microneedles are methacrylamide gelatin soluble microneedles.

7. The application according to claim 6, characterized in that, The method for preparing methacrylamide gelatin-soluble microneedles loaded with artemisia annua nanovesicles is as follows: a suspension of artemisia annua nanovesicles is mixed with a methacrylamide gelatin solution, a photoinitiator is added, and the mixture is thoroughly mixed to obtain a methacrylamide gelatin prepolymer solution loaded with nanovesicles; the prepolymer solution is injected into a microneedle mold and photocured for crosslinking to obtain the microneedles.

8. The application according to claim 7, characterized in that, The photoinitiator is 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone.

9. The application according to claim 7, characterized in that, The mass ratio of artemisia annua nanovesicles to methacrylamide gelatin is 1:100~300.

10. The application according to claim 1, characterized in that, The drug is a transdermal administration formulation.

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