Method for constructing aerogel solid-state drug delivery system for treating blepharitis

Abstract

The invention relates to a method for constructing an aerogel solid drug delivery system for treating blepharitis, which belongs to the field of ophthalmic medical technology. The scheme is as follows: step 1, dissolving a polar drug in an ethanol solution to obtain solution A, adding a metal frame carrier to solution A, stirring, centrifuging, and drying to obtain a polar drug-metal frame delivery system; step 2, fully cross-linking the aerogel material, the polar drug-metal frame delivery system, and a cross-linking agent, adding a volatile oil component and stirring until there are no bubbles to obtain a mixed glue B; or fully cross-linking the aerogel material, the volatile oil component, and the cross-linking agent, stirring until there are no bubbles, breaking them into a thick liquid state, adding a polar drug-metal frame delivery system, and stirring evenly to obtain a mixed glue C; step 3, freeze-drying the mixed glue B or the mixed glue B to obtain an aerogel solid drug delivery system for treating blepharitis. The bactericidal effect of the present invention is significantly higher than that of traditional dressings.

Description

Technical Field

[0001] The present invention belongs to the technical field of ophthalmic medical treatment, and in particular relates to a method for constructing an aerogel solid-state drug delivery system for treating blepharitis. Background Art

[0002] Blepharitis is a subacute to chronic inflammation of the eyelid skin, eyelash follicles, and glands. The eyelid margin is rich in glandular tissue and fatty secretions, making it susceptible to dirt and bacteria, leading to infection. Clinically, it is categorized into three types: scaly, ulcerative, and canthal blepharitis. Scaly is an eczematous dermatitis of the eyelid margin caused by excessive glandular secretions and secondary infection, while ulcerative is caused by Staphylococcal infection of the eyelash follicles and eyelid skin. Blepharitis is a chronic, difficult-to-cure, and recurrent ocular surface disease. Diagnosis and treatment utilize a combination of antibiotics, Chinese herbal fumigation, topical application, oral administration, and ultrasonic atomization to improve symptoms and signs, but many challenges remain. Long-term treatment with eye cleansers is expensive, and some patients still experience poor results or relapses. Immune factors may play a significant role in the onset and recurrence of the disease. Therefore, leveraging the holistic principles of Traditional Chinese Medicine (TCM), its simplicity, convenience, and cost-effectiveness, and using a syndrome-based approach to improve the immune system to shorten treatment cycles and reduce recurrences, is an urgent need. Ruyi Jinhuang San (RHS) was first recorded in the Ming Dynasty's "Surgery Authentic", which said: "It can be used to treat all kinds of stubborn swellings and poisons in surgery, and it will be effective." It is included in the 2nd to 11th editions of the "Chinese Pharmacopoeia". It has the effects of clearing away heat and detoxifying, reducing swelling and relieving pain. It is mainly used for sores, swelling and pain caused by heat and toxic stagnation in the skin, and erysipelas. The symptoms are redness, swelling, heat and pain in the skin. It can also be used for traumatic injuries. Modern research shows that RHS can significantly improve wound healing. RHS is an immunomodulator. [1] Its active ingredients can inhibit the expression of pro-inflammatory factors iNOS and COX-2 in macrophages, and can also inhibit the production of cytokines in plasma, so it has the effect of relieving physical pain.

[0003] An ideal wound dressing should possess a variety of functional properties, including a suitable surface structure, sufficient mechanical strength, high gas permeability, excellent biocompatibility, and effective antibacterial properties. Aerogels have a high specific surface area, allowing for rapid absorption of exudate; their high porosity ensures gas exchange between the wound and the outside world; and their unique three-dimensional network structure facilitates cell adhesion, proliferation, vascularization, and tissue reconstruction, thus offering unique advantages in wound repair. An increasing number of aerogels with different compositions and structures are being used to repair different types of wounds. López-Iglesias C [2] et al. prepared chitosan aerogel loaded with vancomycin. The release curve showed that the drug can be released quickly and can effectively achieve local therapeutic levels. Antibacterial tests showed that it has good cell compatibility and can effectively prevent high bacterial loads in wounds. [3]et al. prepared a flexible antibacterial aerogel based on nanocellulose, in which the loaded cinnamaldehyde, microfibrillated cellulose and nanocrystals interacted to form an antibacterial surface with a dense and uniform microstructure, which had long-term excellent antibacterial activity.

[0004] Metal organic frameworks (MOFs) are mainly metal-organic supramolecular network structures formed by the coordination of multidentate ligands with metal centers. Compared with other porous carrier materials, they have the following advantages: highly ordered pore structure, controllable pore size, and controllable functional groups and surface potential energy on the pore surface. Dong K et al. [4] loaded camptothecin into RGD-modified ZIF-8 metal organic frameworks, showing good targeting and therapeutic effects, and are expected to become potential drugs for targeted tumor therapy.

[0005] References:

[0006] [1]YuKwongleung,ChouYichun,Liu Chingshen,ChenYijia,YenMinghong.InducibleExpressionofNOS andCOX-2inEvaluating the Effects ofRuyi-JinhuangGao on S-omaticPain-Associated Inflammation[J].JournalofFood andDrugAnalysis.2005,13(3):225-231.

[0007] [2]López-Iglesias C,Barros J,Ardao I,Monteiro FJ,Alvarez-Lorenzo C,Gómez-AmozaJL,García-GonzálezCA.Vancomycin-loadedchitosan aerogelparticlesforchronicwo-undapplications[J].Carbohydr Polym.2019,15(204):223-231.

[0008] [3] Saini A, Yadav C, Sethi SK, Xue BL, Xia Y, LiK, Manik G, Li

[0009] [4]DongK, ZhangY, Zhang L, Wang Z, RenJ, QuX. Facilepreparationofmetal-orga-nic frameworks-based hydrophobic anticancerdrug delivery nanoplatform for targetedandenhancedcancer treatment[J].Talanta.2019,194:703-708. Summary of the Invention

[0010] The present invention provides a method for constructing an aerogel solid drug delivery system for treating blepharitis. The specific technical solution is as follows:

[0011] A method for constructing an aerogel solid drug delivery system for treating blepharitis comprises the following steps:

[0012] Step 1: dissolving a polar drug in anhydrous ethanol to obtain solution A, adding a dried and activated metal framework carrier to solution A, stirring, centrifuging, and drying to obtain a polar drug-metal framework drug delivery system; the polar drug is a substance extracted from Ruyi Jinhuang Powder using a 30% alcohol solution by mass; the metal framework carrier comprises a combination of one or more of CuBTC and IRMOF-3;

[0013] Step 2: After fully cross-linking the glacial acetic acid solution of the aerogel material, the polar drug-metal frame drug delivery system, and the cross-linking agent, the mixture is added with the volatile oil component and stirred until no bubbles are formed to obtain a mixed glue solution B; or after fully cross-linking the glacial acetic acid solution of the aerogel material, the volatile oil component, and the cross-linking agent, the mixture is stirred until no bubbles are formed to obtain a volatile oil component-aerogel, the volatile oil component-aerogel is crushed into a thick liquid state, the polar drug-metal frame drug delivery system is added, and the mixture is stirred evenly to obtain a mixed glue solution C; the aerogel material comprises a combination of one or more of chitosan, sodium alginate, silk fibroin, and polyvinyl alcohol; the volatile oil component is volatile oil extracted from Ruyi Jinhuang Powder by steam distillation or supercritical carbon dioxide; and the cross-linking agent is a 2% by mass calcium chloride aqueous solution;

[0014] Step 3: freeze-drying the mixed glue solution B or the mixed glue solution C to obtain an aerogel solid drug delivery system for treating blepharitis.

[0015] Furthermore, in step 1, the mass fraction of the polar drug in solution A is 20%-80%.

[0016] Furthermore, in step 1, the mass ratio of the polar drug to the metal frame carrier is 1:2.

[0017] Furthermore, in step 2, the mass ratio of the aerogel material, the polar drug-metal frame drug delivery system, the cross-linking agent and the volatile oil component is 15:40:5:40.

[0018] Furthermore, in step 2, the mass fraction of the glacial acetic acid solution is 60%, and the mass fraction of the aerogel material in the glacial acetic acid solution of the aerogel material is 3%.

[0019] Furthermore, in step 2, the temperature at which the cross-linking reaction occurs is controlled at -20°C to 40°C.

[0020] Furthermore, in step 1, the stirring time is 1-8 hours, the drying temperature is 80° C., and the drying time is 12 hours.

[0021] Furthermore, in step 3, the mixed glue solution B or the mixed glue solution C is dispersed on a multi-well plate, 0.2-0.8 mL is added to each well, and then freeze-dried.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] The present invention uses the organic metal framework as a carrier and also as an antibacterial absorbent dressing, releasing metal ions to kill bacteria when absorbing exudate. There are many similar effects of heavy metals in ancient Chinese medical books. For example, the "Kaibao Materia Medica" mentions that the main treatment of copper is "to treat fractures, disperse blood and stop pain, and break up accumulations." Modern research shows that its mechanism of action is mainly based on the denaturing effect of heavy metal ions on cell proteins, which rarely produces drug-resistant bacteria. The present invention needs some new antibiotic-free antibacterial drugs to treat bacterial infections. In the present invention, the organic metal framework is wrapped in an aerogel pore structure, so that the metal ions are gradually released, which can avoid excessive deposition of metal ions, significantly improve its bactericidal activity, and the bactericidal effect is significantly higher than that of traditional dressings. It can be made into an eye patch to play an antibacterial and synergistic role. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a scanning electron microscope image of the aerogel solid-state drug delivery system for treating blepharitis constructed by the doping method of the present invention;

[0025] Figure 2 It is the adsorption-desorption isotherm of the aerogel solid-state drug delivery system for the treatment of blepharitis constructed by the doping method of the present invention, wherein ADS is the adsorption curve; DES is the desorption curve, Va refers to the adsorption amount of N2, STP refers to the standard state: 273.15K, 100kPa, P / P0 is the relative pressure, P0 represents the saturated vapor pressure of the gas at the adsorption temperature, and P represents the pressure of the gas phase at adsorption equilibrium. DETAILED DESCRIPTION

[0026] The technical solutions of the present invention will be clearly and completely described below in conjunction with the accompanying drawings and embodiments. Obviously, the described embodiments are only part of the embodiments of the invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0027] Example 1

[0028] In situ synthesis of an aerogel drug delivery system for the treatment of blepharitis

[0029] Take 500g of the medicinal materials in the prescription of Ruyi Jinhuang Powder, steam distill to obtain the volatile oil component, add 3500ml of 30% ethanol solution to the distillation residue, reflux extract 3 times, each time for 1 hour, collect the extract and concentrate it to a density of 1.5g / cm 3 The thick paste is a polar drug.

[0030] 100 mg of a polar drug was accurately weighed and completely dissolved in 200 ml of anhydrous ethanol at 25°C to obtain solution A. 200 mg of dried and activated CuBTC nanocarriers were accurately weighed and added to solution A. Drug loading was achieved by magnetic stirring for 6 hours. The solution was centrifuged at 10,000 rpm for 5 minutes to remove excess polar drug ethanol solution. The precipitate was collected and dried in a vacuum drying oven at 80°C for 12 hours to obtain drug-loaded nanoparticles, i.e., the polar drug-metal framework drug delivery system.

[0031] A 3% mass fraction of aerogel material (chitosan) in glacial acetic acid solution (the mass fraction of the glacial acetic acid solution is 60%), a polar drug-metal frame drug delivery system and a crosslinking agent (a 2% mass fraction of calcium chloride aqueous solution) were mixed and placed in a 25°C environment for full crosslinking; the volatile oil component was added and stirred until there were no bubbles; the crosslinked mixed glue was poured into a 24-well plate (the bottom diameter of the single well was 15.6 mm and the area was 1.9 cm 2 ), add 0.6 mL of liquid to each well, and cool. The 24-well plate was pre-frozen in a -20°C refrigerator for 24 hours. The plate was then freeze-dried in a vacuum freeze dryer at -20°C and 1.0 mBar for 12 hours. The metal frame / aerogel drug delivery system, i.e., the aerogel solid-state drug delivery system for the treatment of blepharitis (Sample I), was obtained. The mass ratio of the aerogel material, the polar drug-metal frame drug delivery system, the crosslinker, and the volatile oil component was 15:40:5:40.

[0032] Example 2

[0033] Construction of an aerogel drug delivery system for the treatment of blepharitis by doping

[0034] A glacial acetic acid solution (the mass fraction of the glacial acetic acid solution is 60%) of a 3% mass fraction of aerogel material (chitosan), a volatile oil component and a cross-linking agent (2% calcium chloride aqueous solution) are mixed evenly and placed in an environment of 25°C for full cross-linking. The mixture is stirred until there are no bubbles to prepare a volatile oil component-aerogel; a homogenizer is used to break it into a thick liquid state, and the polar drug-metal frame drug delivery system prepared by the method in Example 1 is added, stirred until the mixture is uniform, and freeze-dried to obtain a metal frame / aerogel drug delivery system, that is, an aerogel solid drug delivery system (sample II) for the treatment of blepharitis; wherein the mass ratio of the aerogel material, the polar drug-metal frame drug delivery system, the cross-linking agent and the volatile oil component is 15:40:5:40.

[0035] Evaluation index system

[0036] Ⅰ Exploring drug release patterns using quantitative fingerprints

[0037] A multi-index quantitative fingerprint method was used to determine the content of each indicator by GC and LC. The in vitro release was determined using a Franz diffusion cell test. Samples were taken every hour within 12 hours, and the fingerprints at different times were measured. β-eudesmol, zinger flavonoids, glycyrrhizin, rhein, berberine, genistein, and glycyrrhizin G2 in the sample were used as indicators to determine the in vitro cumulative release rate. The original total content of each component in the original extract was considered as the amount released at 100%, and the release amount at different times was calculated using the ratio of the corresponding peak areas. The cumulative release formula is shown in Formula I:

[0038]

[0039] t is time (h); Q t is the cumulative release at time t (%); C t is the concentration at time point t (measured in peak area); V0 is the total volume of the dissolution medium (900 mL); C i is the concentration at time point i (measured in peak area); V i is the sampling volume at time point i; M is the content of each component (measured in peak area).

[0040] Table 1 Release data of sample I obtained by in-situ synthesis method described in Example 1

[0041]

[0042] Table 2 Release data of sample II obtained by doping method described in Example 2

[0043]

[0044]

[0045] From the comparison of the drug release data in Table 1 and Table 2, it can be seen that the aerogel drug delivery system for the treatment of blepharitis constructed by the doping method releases the drug more completely, so the doping method is selected as the preferred synthesis method.

[0046] Ⅱ Determination of physical properties

[0047] Microscopic morphology characterization: The microstructure of Sample II obtained by the doping method described in Example 2 was observed using a field emission scanning electron microscope. The sample to be tested was carefully cut with a scalpel into 5 mm × 5 mm, 2.5 mm thick samples. The cross section was placed upward on a copper table with conductive adhesive attached and fixed. The sample was then gold-sprayed using a sputtering method. Finally, the microscopic morphology of the sample cross section was observed using a scanning electron microscope. Figure 1 shown.

[0048] Specific surface area calculation: Sample II was vacuum degassed at 120 ° C for 3 h, and the N2 adsorption-desorption isotherm was measured using a specific surface area analyzer (BET). Figure 2 As shown in Table 3, the isotherm curve exhibits a closed loop structure, demonstrating the presence of microporous structures in the support. The surface area measurement results for Samples I and II are shown in Table 3. The results show that the support prepared by the doping method has a higher specific surface area, pore volume, and pore diameter.

[0049] Table 3 Micropore structure determination of sample I and sample II

[0050] Sample name <![CDATA[Specific surface area / (m 2 ·g -1 )]]> <![CDATA[Pore volume / (cm 3 ·g -1 )]]> Pore ​​diameter / (nm) Preparation of sample I by in situ synthesis 0.252 0.001 16.285 Sample II prepared by doping method 1.593 0.010 25.252

[0051] Calculation of carrier loading capacity: Using a thermogravimetric analyzer (TG), 3 to 8 mg of sample was taken and placed in an alumina crucible. In a nitrogen atmosphere with a flow rate of 30 mL / min, the heating rate was 20°C / min, and the temperature range was 30°C to 800°C. The ash content of the four samples, aerogel, metal frame, sample I and sample II, was measured. The carrier loading capacity was calculated using the following formula VI. The results are shown in Table 4. The carrier prepared by the doping method also has a higher drug loading capacity and is more suitable for drug loading.

[0052]

[0053] Table 4: Calculation of loading rates for samples I and II

[0054]

[0055] Ⅲ Three-dose method to calculate in vitro antibacterial potency and cell-mediated immunity to evaluate in vitro anti-inflammatory activity

[0056] (1) Calculation of in vitro antibacterial potency

[0057] Appropriate amounts of Ruyi Jinhuang Powder, metal frame, and sample II were weighed and diluted with pH 7.8 phosphate buffer to form standard, metal frame, and test solutions, respectively. Third-generation cultures of Staphylococcus aureus and Escherichia coli were prepared into bacterial suspensions with a turbidity of 0.5 McFarland turbidimetric (McFarland) for each. Two flat-bottomed double-dishes were filled with 20 mL of heat-sterilized, melted culture medium. Separate sterile culture medium was melted and allowed to cool to 48-50°C. Two portions were added with 1% of each of the two bacterial suspensions, shaken well, and poured into two flat-bottomed double-dishes, with 5 mL added to each. The mixture was evenly spread. After cooling, each dish was placed into eight Oxford cups for later use. Using the three-dose method, the standard solution, metal frame solution, and three different doses of the test sample (high, medium, and low) were added to the Oxford cups. Five samples were prepared for each bacterial suspension, in triplicate. After incubation at 37°C for 18 hours, the diameters of the inhibition zones were measured, and the samples were tested and potency calculated using bioassay statistics. The mass fraction of the test solution in the high-dose group was 80%, the mass fraction of the test solution in the medium-dose group was 50%, the mass fraction of the test solution in the low-dose group was 20%, the concentration of Ruyi Jinhuang San solution was 50 mg / L; the concentration of the metal frame solution was 50 mg / L.

[0058] Table 5: Effects of five samples on the diameter of inhibition zone of two bacteria ( n=3)

[0059]

[0060] Table 5 shows that the diameter of the inhibition zone in the high-dose group was significantly higher than that in the Ruyi Jinhuang San group, while the diameter of the inhibition zone in the medium-dose group was comparable to that in the Ruyi Jinhuang San group. Furthermore, the metal frame also exhibited some antibacterial activity. The high-concentration drug delivery system exhibited significantly higher antibacterial effects against Staphylococcus aureus and Escherichia coli than the Ruyi Jinhuang San group, demonstrating its superior antibacterial efficacy.

[0061] (2) Evaluation of anti-inflammatory activity in vitro

[0062] RAW264.7 cells were revived, passaged, and plated in high-glucose DMEM medium. The cell density was adjusted and the cells were seeded in 96-well plates. A blank group received only high-glucose DMEM medium, while the control, model, and experimental groups received medium containing 10 μg / mL LPS to establish a cellular inflammation model. After incubation for 4 hours, the cells were discarded. High-glucose DMEM medium was added to the blank and control groups, while a 10% solution of Sample II prepared in high-glucose DMEM was added to the experimental group and incubated for 24 hours. ELISA kits were used to detect the inhibitory effects of each solution on inflammatory factors.

[0063] The experimental results in Table 6 show that VEGF and IL-6 levels in the model group were higher than those in the blank group, confirming the successful establishment of the model. VEGF and IL-6 concentrations in both the experimental and control groups showed a downward trend, with the experimental group outperforming the control group. This suggests that this drug delivery system has a strong therapeutic effect on inflammation.

[0064] Table 6 Effects of sample II on VEGF (vascular endothelial growth factor) and IL-6 (interleukin-6) in the inflammation model ( n=3)

[0065]

[0066] Note: n=3, There were significant differences between each group and the blank group, *P<0.05.

[0067] Ⅳ Digital image quantification technology and enzyme-linked immunosorbent assay to determine pharmacodynamic indicators

[0068] SD rats were randomly divided into a model group, a positive control group, and an experimental group. The model group, like the blepharitis group, was given normal saline. The positive control group was given the ethanol extract of Ruyi Jinhuang San (a polar drug) after model establishment. The experimental group was given Sample II after model establishment. Each group consisted of 12 rats. Dressings were changed daily and the wounds were observed until complete healing. Every other day, digital images of the wounds were captured using a digital camera at a 2cm macro distance. Image processing and analysis were performed using ImageJ. The processing process included calibration, binarization, background removal, thresholding, data analysis, and final healing time was recorded, and the wound healing rate was calculated.

[0069] Wound healing rate (%) = (initial area - current measured area) / initial area × 100%

[0070] The data obtained is used SPSS statistical software was used for data analysis, and one-way analysis of variance was used for comparison among groups.

[0071] On the 14th day after the intervention, rats were anesthetized and euthanized by cervical dislocation. One gram of tissue was collected from each rat's wound, collected separately, homogenized, and then transferred to a 10-mL centrifuge tube. 3 mL of RIPA buffer was added on ice. After incubation on ice for 2 hours, the tubes were centrifuged at 10,000 rpm at 4°C for 10 minutes. The supernatant was transferred to a fresh centrifuge tube, aliquoted, and stored at -20°C for subsequent experiments. Interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and mitogen-activated protein kinase 8 (MAPK8) levels were measured. After the ELISA reaction, the absorbance was read on a microplate reader, and the levels of each assay were calculated. The wound and surrounding skin tissue were collected, fixed, and preserved. After hematoxylin-eosin staining, the tissue and cellular ultrastructure were observed using electron microscopy and transmission electron microscopy to evaluate the effect of sample II on blepharitis wound healing.

[0072] Table 7 Comparison of wound closure area in rats

[0073]

[0074] Note: n=6, There were significant differences between each group and the blank group, *P<0.05.

[0075] The results, as shown in Table 7, showed no significant postoperative wound infection in any group of rats. After 14 days, the wounds in the positive control group were essentially healed. The wound healing in the model group was significantly slower, with a statistically significant difference (P < 0.05). The wounds in the experimental group had significantly improved. As shown in Table 8, the rat growth factor assay demonstrated that this drug delivery system significantly reduced four inflammatory markers, surpassing the control group.

[0076] Table 8 Effects of metal frame / aerogel drug delivery system on growth factors in rat model ( n=3)

[0077]

[0078] Note: n=3, There were significant differences between each group and the negative control group (*P<0.05).

[0079] Ⅴ Toxicity and irritation evaluation

[0080] Cell proliferation assay (CCK method) to evaluate cytotoxicity

[0081] Sterilize sample II under ultraviolet light for 24 hours. Place the sterilized sample in 10mL of DMEM culture medium containing 10% serum prepared in advance as the extraction medium, and centrifuge at 1000rpm after extraction. Add 3T3 cells in the logarithmic growth phase to the extract. At the same time, the high, medium, and low experimental groups, the blank group (no cells) and the control group (100μL cell suspension) were added with DMEM culture medium containing 10% fetal bovine serum, and placed in a constant temperature incubator at 37°C and 5% CO2 for 24h, 48h, and 72h, respectively. Use an enzyme-labeled instrument to detect the OD value (absorbance value) at 450nm, and calculate the relative cell proliferation rate P according to the formula:

[0082] P=(OD 实验组 -OD 空白组 ) / (OD 对照组 -OD 空白组 )×100%

[0083] Table 9 Relative proliferation rate of sample II at different concentrations (%)

[0084]

[0085]

[0086] The results in Table 9 show that neither high nor low concentrations of Sample II have any effect on the relative cell proliferation rate.

[0087] In addition, it should be understood that although this specification is described in terms of implementation methods, not every implementation method contains only one independent technical solution. This narrative method of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment can also be appropriately combined to form other implementation methods that can be understood by those skilled in the art.

Claims

1. A method for constructing an aerogel solid drug delivery system for treating blepharitis, characterized in that: The following steps are involved: Step 1: dissolving a polar drug in anhydrous ethanol to obtain solution A, adding the dried and activated metal frame carrier to solution A, stirring, centrifuging, and drying to obtain a polar drug-metal frame drug delivery system; the polar drug is a substance extracted from Ruyi Jinhuang Powder using a 30% alcohol solution; the metal frame carrier is CuBTC; the mass fraction of the polar drug in solution A is 20%-80%, and the mass ratio of the polar drug to the metal frame carrier is 1:2; Step 2: After the glacial acetic acid solution of the aerogel material, the polar drug-metal frame drug delivery system and the cross-linking agent are mixed and fully cross-linked, the volatile oil component is added and stirred until there are no bubbles to obtain a mixed glue B; or after the glacial acetic acid solution of the aerogel material, the volatile oil component and the cross-linking agent are mixed and fully cross-linked, the volatile oil component and the cross-linking agent are stirred until there are no bubbles to prepare a volatile oil component-aerogel, the volatile oil component-aerogel is crushed into a thick liquid state, the polar drug-metal frame drug delivery system is added, and the mixed glue C is obtained; the aerogel material is chitosan; the volatile oil component is the volatile oil extracted from Ruyi Jinhuang Powder by steam distillation or supercritical carbon dioxide; the cross-linking agent is a calcium chloride aqueous solution with a mass fraction of 2%; the mass ratio of the aerogel material, the polar drug-metal frame drug delivery system, the cross-linking agent and the volatile oil component is 15:40:5:40; Step 3: freeze-drying the mixed glue solution B or the mixed glue solution C to obtain an aerogel solid drug delivery system for treating blepharitis.

2. The method for constructing an aerogel solid drug delivery system for treating blepharitis according to claim 1, characterized in that: In step 2, the mass fraction of the glacial acetic acid solution is 60%, and the mass fraction of the aerogel material in the glacial acetic acid solution of the aerogel material is 3%.

3. The method for constructing an aerogel solid drug delivery system for treating blepharitis according to claim 1, characterized in that: In step 2, the temperature at which the cross-linking reaction occurs is controlled at -20°C to 40°C.

4. The method for constructing an aerogel solid drug delivery system for treating blepharitis according to claim 1, characterized in that: In step 1, the stirring time is 1-8 hours, the drying temperature is 80° C., and the drying time is 12 hours.

5. The method for constructing an aerogel solid drug delivery system for treating blepharitis according to claim 1, characterized in that: In step 3, the mixed glue solution B or mixed glue solution C is dispersed on a multi-well plate, 0.2-0.8 mL is added to each well, and then freeze-dried.

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