Sodium hyaluronate-dexamethasone nanoparticles, and preparation method and application thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and provides sodium hyaluronate-dexamethasone nanoparticles as well as a preparation method and application thereof. The method comprises the following steps: dissolving dexamethasone in ethanol to obtain a dexamethasone-ethanol solution, dissolving sodium hyaluronate in an aqueous solvent to obtain a sodium hyaluronate aqueous solution, and preheating the sodium hyaluronate aqueous solution; then synchronously injecting the dexamethasone-ethanol solution serving as a lipid phase and the preheated sodium hyaluronate aqueous solution serving as a water phase into a microfluidic mixing channel at a set total flow velocity and a flow velocity ratio of the lipid phase to the water phase by adopting a microfluidic synthesis device, and forming a sodium hyaluronate-dexamethasone nanoparticle dispersion liquid in situ in the channel; and if necessary, further dispersing in a phosphate buffer solution. The obtained nanoparticles have the advantages of small particle size, good dispersity, high stability, convenience in surface modification and the like, and can be used for preparing medicines for preventing or treating inflammatory diseases.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, and in particular to a method for preparing sodium hyaluronate-dexamethasone nanoparticles and the resulting nanoparticles and pharmaceutical compositions, which can be used for the prevention or treatment of inflammatory diseases. Background Technology

[0002] Sodium hyaluronate is the sodium salt of hyaluronic acid (HYA), a dextranuronic acid found in the extracellular matrix of various tissues. It possesses anti-inflammatory properties and plays a crucial role in tissue regeneration. Due to its excellent support and scalability, it can effectively co-encapsulate different active molecules to form nanoparticles, achieving highly efficient drug delivery.

[0003] Dexamethasone (DEX) is a glucocorticoid widely used to treat allergic and autoimmune diseases, particularly playing a crucial role in lung-related conditions. However, long-term administration of dexamethasone can lead to serious side effects such as kidney failure. Encapsulating dexamethasone with sodium hyaluronate can improve delivery efficiency while reducing dosage. However, sodium hyaluronate-dexamethasone nanoparticles prepared by traditional stirring methods suffer from poor uniformity and stability due to their large particle size and dispersibility index. This results in low drug bioavailability. Furthermore, the low uniformity makes surface modification difficult and hinders the connection of targeted molecules such as peptides, further reducing its practical application. In addition, the traditional stirring method requires two steps: first preparing dexamethasone particles, and then further encapsulating them with sodium hyaluronate. This involves numerous variables and makes scale-up difficult. Summary of the Invention

[0004] To overcome the problems of large particle size, high dispersibility index, poor particle uniformity and stability in the preparation of sodium hyaluronate-dexamethasone nanoparticles by traditional stirring methods, resulting in low drug bioavailability and difficulty in surface modification with targeted molecules such as peptides, and the fact that existing processes usually require the preparation of dexamethasone particles before encapsulation into sodium hyaluronate, which involves multiple steps and is difficult to scale up, this invention provides a method for preparing sodium hyaluronate-dexamethasone nanoparticles and the resulting nanoparticles and drug composition. In this method, by combining specific preheating and curing heating conditions during microfluidic mixing, efficient encapsulation and nano-sizing of dexamethasone within the sodium hyaluronate framework are achieved, resulting in nanoparticles with small particle size, good dispersibility, and excellent stability, thereby improving the specific surface area and bioavailability of the particles; at the same time, microfluidic preparation significantly simplifies the process and improves preparation efficiency.

[0005] According to a first aspect of the present invention, a method for preparing sodium hyaluronate-dexamethasone nanoparticles is provided, comprising the following steps: (1) Preparation of lipid phase: Dexamethasone was dissolved in ethanol to obtain dexamethasone-ethanol solution; (2) Preparation of aqueous phase: Dissolve sodium hyaluronate in an aqueous solvent to obtain an aqueous solution of sodium hyaluronate; (3) Preheat the sodium hyaluronate aqueous solution at 25-55°C for 1-10 min; (4) Preheat the dexamethasone-ethanol solution at 25~55℃ for 1~5 min; (5) Using a microfluidic synthesis device, the dexamethasone-ethanol solution is used as the lipid phase and the preheated sodium hyaluronate aqueous solution is used as the aqueous phase. The solution is injected into the microfluidic mixing channel at a set total flow rate and a lipid phase to aqueous phase flow rate ratio, so that the two are mixed in the microfluidic mixing channel and form a sodium hyaluronate-dexamethasone nanoparticle dispersion in situ. (6) The nanoparticle dispersion obtained in step (5) is heated at 25-50℃ for 1-15 min to solidify it, thereby obtaining solidified sodium hyaluronate-dexamethasone nanoparticles.

[0006] This solution uses a microfluidic chip and precisely controls the inflow of liquid through a microfluidic instrument; the microfluidic chip contains a microfluidic mixing channel designed based on the principles of laminar or turbulent mixing.

[0007] In some technical solutions, the concentration of dexamethasone in the dexamethasone-ethanol solution is 1-10 mg / mL, and the concentration of sodium hyaluronate in the sodium hyaluronate aqueous solution is 0.69-5 mg / mL.

[0008] In some technical solutions, the dexamethasone-ethanol solution and the sodium hyaluronate aqueous solution prepared in steps (1) and (2) are filtered through a 0.22 μm hydrophobic filter membrane before entering the microfluidic synthesis device to remove tiny solid particles.

[0009] In some technical solutions, the total flow rate of the microfluidic synthesis device in step (5) is 4 to 40 mL / min; the flow rate ratio of the lipid phase to the aqueous phase is 1:0.5 to 1:10.

[0010] In some technical solutions, after step (5) and / or step (6), the sodium hyaluronate-dexamethasone nanoparticles are further dispersed in phosphate buffer to improve the particle size stability of the nanoparticles.

[0011] In some technical solutions, the average particle size of the sodium hyaluronate-dexamethasone nanoparticles is 40-700 nm, and the polydispersity index is 0.20-0.60.

[0012] According to a second aspect of the present invention, a sodium hyaluronate-dexamethasone nanoparticle is further provided, the nanoparticle being composed of sodium hyaluronate and dexamethasone, and being prepared by the above-described preparation method.

[0013] In some technical solutions, the average particle size of the nanoparticles is 40–700 nm, and the PDI is 0.20–0.60.

[0014] According to a third aspect of the invention, a pharmaceutical composition is further provided, the pharmaceutical composition comprising the above-described sodium hyaluronate-dexamethasone nanoparticles and a pharmaceutically acceptable carrier or excipient.

[0015] According to a fourth aspect of the invention, the use of the above-described pharmaceutical composition in the preparation of a medicament for the prevention or treatment of inflammatory diseases is further provided.

[0016] The present invention, by employing the above technical solution, has at least the following beneficial effects: 1. This invention employs a technique of simultaneously injecting dexamethasone-ethanol solution and sodium hyaluronate aqueous solution into a microfluidic mixing channel for in-situ granulation. Compared to traditional mechanical stirring or two-step granulation processes, this achieves rapid mixing and uniform nucleation within a microscale space, significantly reducing macroscopic fluctuations in the nucleation and growth environment. Furthermore, preheating the sodium hyaluronate aqueous solution before synthesis and heating and solidifying the resulting nanoparticle dispersion result in a more uniform distribution and denser structure of dexamethasone within the sodium hyaluronate network. Compared to control systems without preheating and solidification or using conventional stirring methods, the nanoparticles obtained using this invention exhibit significantly smaller particle sizes, more concentrated particle size distribution, and a significantly lower PDI (particulate density) measured by dynamic light scattering, demonstrating excellent uniformity and batch-to-batch repeatability.

[0017] 2. This invention achieves controllable key quality attributes of nanoparticles through systematic optimization of process parameters such as the concentration of dexamethasone-ethanol solution, the concentration of sodium hyaluronate aqueous solution, the total microfluidic flow rate, and the ratio of lipid phase to aqueous phase flow rate. A balance can be achieved between particle size, drug loading, and dispersibility according to specific drug delivery requirements.

[0018] 3. By dispersing the prepared nanoparticles in phosphate buffer, the present invention can further improve the ionic strength and pH environment of the system, significantly improve the particle size stability of the nanoparticles during storage and use, reduce the particle size change over time, and prevent significant aggregation or sedimentation, making them more suitable for clinically usable injectable or topical formulations.

[0019] 4. This invention relies on a microfluidic synthesis device for preparation, which makes the reaction volume small and the residence time controllable, fundamentally reducing batch-to-batch process fluctuations and facilitating digital scale-up by adjusting flow parameters.

[0020] 5. The entire system of this invention uses only pharmaceutically recognized safe components such as ethanol, aqueous solvent, sodium hyaluronate, and dexamethasone, without the need to introduce photoinitiators, chemical cross-linking agents, or complex organic monomers, thus avoiding potential residual risks.

[0021] 6. The sodium hyaluronate-dexamethasone nanoparticles obtained in this invention not only retain the good biocompatibility and tissue affinity of sodium hyaluronate, but also utilize the characteristics of small particle size, high specific surface area and surface modifiability of nanoparticles, which are expected to achieve more efficient and longer-lasting local drug delivery in various inflammatory sites such as joint cavity, eye, and respiratory tract, and have good application prospects. Detailed Implementation

[0022] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of the present invention. The preferred embodiments and materials described herein are for illustrative purposes only.

[0023] The following experimental examples were all synthesized using the following instruments and chips: Instrument: FludicLab-NP-S2; Chip: FludicLab-COC-LNP-B1 (fishbone structure chip).

[0024] Experimental Example 1: Optimization of DEX Concentration in Nanoparticle Synthesis Reagent concentrations: DEX ethanol solutions of different concentrations; HYA aqueous solution at 1.379 mg / mL.

[0025] As shown in Table 1, the effect of different concentrations of DEX on the particle size of HYA-DEX nanoparticles was investigated using 2.5 mg / mL, 5 mg / mL, 10 mg / mL, and 15 mg / mL DEX as raw materials. The results in Table 1 show that with increasing DEX concentration, the particle size of the nanoparticles first decreases and then increases. The HYA-DEX nanoparticles prepared with 5 mg / mL DEX have the smallest particle size and the most uniform particle size distribution. The particle size and dispersibility can be controlled by adjusting the DEX concentration.

[0026]

[0027] Experimental Example 2: Optimization of HYA Concentration in Nanoparticle Synthesis Reagent concentrations: 5 mg / mL DEX ethanol solution; HYA aqueous solutions of different concentrations.

[0028] Microfluidic parameters: Total flow rate: 10 mL / min; Flow rate ratio (lipid phase: aqueous phase = 1:3); Initial waste liquid: 0.3 mL; Ultrapure water diluted 10 times for detection.

[0029] The effect of different concentrations of HYA on the particle size of HYA-DEX nanoparticles was investigated using concentrations of 0.690 mg / mL, 1.379 mg / mL, 2.758 mg / mL, 3.448 mg / mL, and 6.895 mg / mL. The results are shown in Table 2. A HYA aqueous solution of 1.379 mg / mL yielded the smallest HYA-DEX nanoparticles with high uniformity. Particle size and dispersibility could also be controlled by adjusting the HYA concentration.

[0030]

[0031] Experimental Example 3: The Effect of Different Diluents on Detection Results Reagent concentrations: 5 mg / mL DEX ethanol solution; 1.379 mg / mL HYA aqueous solution.

[0032] Microfluidic parameters: Total flow rate: 10 mL / min; flow rate ratio (lipid phase: aqueous phase = 1:3); initial waste liquid: 0.3 mL; heating of the aqueous phase at 40 °C for 3 min; dilution of the product to 1 mg / mL using different dilution solutions for detection.

[0033] Ultrapure water, 1xPBS, Tris-HCl (pH 7.0), Tris-HCl (pH 7.5), and Tris-HCl (pH 8.0) were used as dilution solvents to investigate the effects of different dilution solvents and pH on the particle size of HYA-DEX nanoparticles. Table 5 shows that 1xPBS is suitable as a dilution solvent for subsequent experiments measuring DLS data of nanoparticles.

[0034]

[0035] Experimental Example 4: Effect of Preheating on the Synthesis of DEX-HYA Nanoparticles Considering that both DEX and HYA have low solubility, heating the reagents to promote dissolution is considered.

[0036] Reagent concentrations: 5 mg / mL DEX ethanol solution; 1.379 mg / mL HYA aqueous solution.

[0037] Microfluidic parameters: Total flow rate: 10 mL / min; flow rate ratio (lipid phase: aqueous phase = 1:3); waste liquid: 0.3 mL; heating different phases at 40 °C for 3 min; product diluted to 1 mg / mL with PBS for detection.

[0038] Before microfluidic synthesis of the product, four sets of experiments were conducted: no heating of the lipid phase and aqueous phase, heating of the lipid phase, heating of the aqueous phase, and heating of both the lipid phase and aqueous phase. The phases were heated at 40℃ for 3 minutes to investigate the effect of different preheating phases on the particle size of HYA-DEX nanoparticles. Table 6 shows that the nanoparticles were the smallest and had better uniformity when only the aqueous phase was heated. Therefore, the aqueous phase was preheated in subsequent experiments.

[0039]

[0040] Experimental Example 5: Effect of Preheating Temperature on the Synthesis of DEX-HYA Nanoparticles Reagent concentrations: 5 mg / mL DEX ethanol solution; 1.379 mg / mL HYA aqueous solution.

[0041] Microfluidic parameters: Total flow rate: 10 mL / min; Flow rate ratio (lipid phase: aqueous phase = 1:3); Initial waste liquid: 0.3 mL; Heating of the aqueous phase at different temperatures; Heating for 3 min; Diluting the product to 1 mg / mL with PBS for detection.

[0042] Before microfluidic synthesis, the aqueous phase was heated for 3 minutes at 35℃, 40℃, 45℃, 50℃, and 55℃ respectively to investigate the effect of different preheating temperatures on the particle size of HYA-DEX nanoparticles. Table 7 shows that the nanoparticles had the smallest particle size and better uniformity when the aqueous phase was preheated at 40℃.

[0043]

[0044] Effect of preheating time on the synthesis of DEX-HYA nanoparticles in Experiment Example 6 Reagent concentrations: 5 mg / mL DEX ethanol solution; 1.379 mg / mL HYA aqueous solution.

[0045] Microfluidic parameters: total flow rate: 10 mL / min; flow rate ratio (lipid phase: aqueous phase = 1:3); initial waste liquid: 0.3 mL; heating of aqueous phase at 40 °C; heating for different durations; product diluted to 1 mg / mL with PBS for detection.

[0046] Before microfluidic synthesis of the product, the aqueous phase was heated at 40℃ for 0 minutes, 3 minutes, 6 minutes and 9 minutes respectively to investigate the effect of different preheating times on the particle size of HYA-DEX nanoparticles. Table 8 shows that the nanoparticles were the smallest and had the best uniformity when the aqueous phase was preheated at 40℃ for 3 minutes.

[0047]

[0048] Experimental Example 7 The dispersibility of the optimized nanoparticles remained high. While some results were good, significant increases in particle size and PDI occurred after only short-term storage (e.g., 4 hours at room temperature). Considering that hyaluronic acid requires heat curing, the heat curing conditions of the product were optimized.

[0049] Reagent concentrations: 5 mg / mL DEX ethanol solution; 1.379 mg / mL HYA aqueous solution.

[0050] Microfluidic parameters: Total flow rate: 10 mL / min; flow rate ratio (lipid phase: aqueous phase = 1:3); waste liquid: 0.3 mL; preheating of aqueous phase at 40 °C for 3 min before synthesis; heating of product at 40 °C; heating for different durations; product diluted to 1 mg / mL with PBS for detection.

[0051] After the product was synthesized by microfluidics, it was heated at 40℃ for 0 minutes, 3 minutes, 6 minutes, 9 minutes, 12 minutes and 15 minutes respectively to investigate the effect of different heating and curing times on the particle size of HYA-DEX nanoparticles. Table 9 shows that the nanoparticles were the smallest and had the best uniformity when the product was heated at 40℃ for 3 minutes.

[0052]

[0053] Comparative example Literature [Camara CI, Bertocchi L, Ricci C, et al. Hyaluronic Acid-Dexamethasone Nanoparticles for Local Adjunct Therapy of Lung Inflammation. Int J Mol Sci [2021;22(19):10480] A relatively traditional method was used to prepare sodium hyaluronate-dexamethasone nanoparticles in a two-step process involving solvent-antisolvent mixing. The synthesis steps are as follows: 1. Dissolve 180 mg of DEX in 36 mL of ethanol.

[0054] 2. At a constant temperature of 25°C, while stirring at a constant speed (165 rpm), slowly add 7 ml of pure water dropwise.

[0055] 3. After a 3-minute interval, slowly add 7 mL of pure water again.

[0056] 4. Repeat step 3, adding a total of 3 times.

[0057] 5. Dissolve 220 mg of high molecular weight (750-1000 kDa) sodium hyaluronate in 14.5 mL of pure water to prepare an aqueous HYA solution.

[0058] 6. Add the entire HYA solution to the DEX nanocrystal suspension described above at once.

[0059] 7. Stir continuously at 280 rpm for 30 minutes at room temperature.

[0060] The particle size and PDI of sodium hyaluronate-dexamethasone in the literature are as follows:

[0061] The results showed that the optimized microfluidic synthesis method had significantly better particle size and PDI than the literature data.

[0062] The following embodiments all use the following microfluidic devices and microfluidic chips: Experimental instrument: FludicLab-NP-S2; Chip: FludicLab-COC-LNP-B1.

[0063] Reagent concentrations: 5 mg / mL DEX ethanol solution; 1.379 mg / mL HYA aqueous solution.

[0064] Example 1: Preferred Experimental Results The results of the above "experimental examples" show that the particle size and dispersion index (PDI) of HYA-DEX nanoparticles can be altered by changing the concentration of HYA solution, the concentration of DEX solution, the total flow rate, the flow rate ratio, the heating time, and the heating temperature. Table 9 summarizes the optimal particle size results for HYA-DEX nanoparticles with small particle size and monodispersity. Both the particle size and PDI are significantly better than the traditional method, and statistical tests show highly significant differences. The experimental steps are as follows: 1) Weigh 180 mg of DEX and add 36 mL of ethanol. If dissolution is difficult, sonication can be used to assist dissolution. Filter using a 0.22 μm PTFE membrane to ensure that the final product does not contain any tiny solid particles, thus obtaining the lipid phase: dexamethasone-ethanol solution.

[0065] 2) Weigh 20 mg of HYA and add it to 14.5 mL of ultrapure water. If dissolution is difficult, sonication can be used to assist dissolution. Filter using a 0.22 μm PTFE membrane to ensure that the final product does not contain any tiny solid particles, thus obtaining the aqueous phase: sodium hyaluronate-water solution.

[0066] 3) Preheat the HYA aqueous solution at 40℃ for 3 min. Set the microfluidic parameters as follows: total flow rate 10 mL / min, flow rate ratio 1:3. After synthesis, heat the product at 40℃ for 3 min to solidify it. Small and uniform HYA-DEX nanoparticles can be obtained.

[0067]

[0068] Example 2: Flow rate optimization under preferred experimental scheme Microfluidic parameters: different total flow rates; flow rate ratio (lipid phase: aqueous phase = 1:3); 0.3 mL of waste liquid before synthesis; preheating of the aqueous phase at 40 °C for 3 min before synthesis; heating of the product at 40 °C for 3 min; dilution of the product to 1 mg / mL with PBS for detection.

[0069] After optimizing all conditions, the particle size results of HYA-DEX nanoparticles synthesized at different total flow rates (mL / min) are summarized in Table 11 below. The particle size and PDI were both superior at a total flow rate of 10 mL / min compared to other total flow rates.

[0070]

[0071] Example 3: Optimization of Flow Rate Ratio under Preferred Experimental Scheme Microfluidic parameters: Total flow rate: 10 mL / min; different flow rate ratios; 0.3 mL of waste liquid before synthesis; preheating of the aqueous phase at 40 °C for 3 min before synthesis; heating of the product at 40 °C for 3 min; dilution of the product to 1 mg / mL with PBS for detection.

[0072] After optimizing all conditions, the particle size results of HYA-DEX nanoparticles synthesized at different flow rate ratios are summarized in Table 11 below. The particle size and PDI are generally better at a flow rate ratio of 1:3 than at other flow rate ratios.

[0073]

[0074] Example 4: Control for unheated solubilization Microfluidic parameters: Total flow rate: 10 mL / min; Flow rate ratio (lipid phase: aqueous phase = 1:3); Pre-waste liquid: 0.3 mL; Product was diluted to 1 mg / mL with PBS for detection.

[0075] After optimizing all conditions, the particle size results of HYA-DEX nanoparticles synthesized without any heating to promote solubility or post-heat curing are summarized in Table 12 below. The particle size and PDI are generally higher than those obtained under other thermosetting conditions, and the experimental results are unstable.

[0076]

[0077] Example 5: Control group treated only with solvent-promoting methods, without post-heat curing. Microfluidic parameters: total flow rate: 10 mL / min; flow rate ratio (lipid phase: aqueous phase = 1:3); waste liquid: 0.3 mL; preheat the aqueous phase at 40 °C for 3 min before synthesis; dilute the product to 1 mg / mL with PBS for detection.

[0078] After optimizing all conditions, the particle size results of HYA-DEX nanoparticles synthesized without thermosetting are summarized in Table 13 below. The particle size and PDI of the product without post-curing treatment are higher than those obtained with post-curing treatment.

[0079]

[0080] This article uses specific examples to illustrate the principles and implementation methods of the present invention. The descriptions of the above embodiments are only for the purpose of helping to understand the method and core ideas of the present invention, including the best mode, and also to enable any person skilled in the art to practice the present invention, including manufacturing and using any device or system, and implementing any combined method. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principles of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing sodium hyaluronate-dexamethasone nanoparticles, characterized in that, Includes the following steps: (1) Preparation of lipid phase: Dexamethasone was dissolved in ethanol to obtain a dexamethasone-ethanol solution; (2) Preparation of aqueous phase: Dissolve sodium hyaluronate in an aqueous solvent to obtain an aqueous solution of sodium hyaluronate; (3) Preheat the sodium hyaluronate aqueous solution at 25-55°C for 1-10 min; (4) Preheat the dexamethasone-ethanol solution at 25-55°C for 1-5 min; (5) Using a microfluidic synthesis device, the dexamethasone-ethanol solution is used as the lipid phase and the preheated sodium hyaluronate aqueous solution is used as the aqueous phase. The solution is injected into the microfluidic mixing channel at a set total flow rate and a lipid phase to aqueous phase flow rate ratio, so that the two are mixed in the microfluidic mixing channel and form a sodium hyaluronate-dexamethasone nanoparticle dispersion in situ. (6) The nanoparticle dispersion obtained in step (5) is heated at 25-50°C for 1-15 minutes to solidify it, thereby obtaining solidified sodium hyaluronate-dexamethasone nanoparticles.

2. The preparation method according to claim 1, characterized in that, The concentration of dexamethasone in the dexamethasone-ethanol solution is 1–10 mg / mL, and the concentration of sodium hyaluronate in the sodium hyaluronate aqueous solution is 0.69–5 mg / mL.

3. The preparation method according to claim 1, characterized in that, The dexamethasone-ethanol solution and the sodium hyaluronate aqueous solution prepared in steps (1) and (2) are filtered through a 0.22 μm hydrophobic filter membrane before entering the microfluidic synthesis device to remove tiny solid particles.

4. The preparation method according to claim 1, characterized in that, The total flow rate of the microfluidic synthesis device in step (5) is 4 to 40 mL / min; the flow rate ratio of the lipid phase to the aqueous phase is 1:0.5 to 1:

10.

5. The preparation method according to claim 1, characterized in that, After step (5) and / or step (6), the sodium hyaluronate-dexamethasone nanoparticles are further dispersed in phosphate buffer to improve the particle size stability of the nanoparticles.

6. The preparation method according to any one of claims 1 to 5, characterized in that, The average particle size of the sodium hyaluronate-dexamethasone nanoparticles is 40–700 nm, and the polydispersity index is 0.20–0.

60.

7. A sodium hyaluronate-dexamethasone nanoparticle, characterized in that, The nanoparticles are composed of sodium hyaluronate and dexamethasone, and are prepared by the preparation method according to any one of claims 1 to 6.

8. The sodium hyaluronate-dexamethasone nanoparticles according to claim 7, characterized in that, The nanoparticles have an average particle size of 40–700 nm and a PDI of 0.20–0.

60.

9. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises the sodium hyaluronate-dexamethasone nanoparticles as described in claim 7 or 8, and a pharmaceutically acceptable carrier or excipient.

10. Use of the pharmaceutical composition of claim 9 in the preparation of a medicament for the prevention or treatment of inflammatory diseases.

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