PSA-Dex polymer nanoparticle, preparation method thereof and application of PSA-Dex polymer nanoparticle in corneal inflammation

Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to PSA-Dex polymer nanoparticles, a preparation method thereof and application of the PSA-Dex polymer nanoparticles in corneal inflammation. The invention firstly provides a sialic acid glycan-dexamethasone polymer nanoparticle for treating inflammatory reaction caused by corneal burn, and the sialic acid glycan-dexamethasone polymer nanoparticle is formed by self-assembly of a sialic acid glycan-dexamethasone polymer. The synthesized nanoparticles can release Dex drugs in a faintly acid eye environment in a responsive manner, so that responsive, efficient, accurate and targeted delivery of the drugs is realized, the cornea penetrating power of the drugs is enhanced, and the effects of enhancing the anti-inflammatory effect and promoting cornea repair are achieved.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to PSA-Dex polymer nanoparticles, a preparation method thereof, and application thereof in corneal inflammation. Background Art

[0002] Corneal burns are common clinical eye injuries and can be categorized as chemical or thermal. Chemical burns cause the most severe corneal inflammation. Chemical burns include both acidic and alkaline burns, with alkaline burns causing far greater damage than acidic burns. Alkaline substances can rapidly penetrate the corneal epithelium, penetrating deep into the corneal stroma and even the anterior chamber, causing extensive tissue necrosis, inflammation, and corneal scarring, ultimately leading to corneal ulcers, perforations, and even blindness. Current treatments for corneal burns primarily focus on anti-inflammatory therapies, infection prevention, and repair. However, existing treatments suffer from low bioavailability, short duration of action, and significant side effects. Dexamethasone (Dex) can suppress inflammation and is used to treat corneal burns. However, conventional dexamethasone (Dex) eye drops have difficulty effectively penetrating the cornea, have a short drug retention time, and exhibit low bioavailability. Long-term or high-dose use can also lead to side effects such as increased intraocular pressure and cataracts. Therefore, how to optimize the delivery method of dexamethasone, increase local drug concentration, and reduce systemic absorption is an urgent breakthrough in the treatment of corneal alkali burns.

[0003] Patent publication number CN109381708A, entitled "A Dexamethasone-Polypeptide Nanoparticle Eye Drop and Its Preparation Method," discloses a dexamethasone-succinic acid-polypeptide chemical bond (Dex-SA-FFFE) that self-assembles into nanoparticles for the treatment of ophthalmic inflammation. The Dex-SA-FFFE described in this patent self-assembles into nanoparticles via a heating-cooling induction process, potentially leading to insufficient long-term stability. Furthermore, the patent does not provide data on the dexamethasone loading. On the other hand, the patent exploits the small size of the prepared Dex-SA-FFFE nanoparticles to enhance the drug's ability to penetrate the corneal barrier, but provides no insight into how the drug is released.

[0004] In summary, it is necessary to propose new improvements to the shortcomings of the existing technology. Summary of the Invention

[0005] The purpose of the present invention is to provide sialoglycan-dexamethasone (PSA-Dex) polymer nanoparticles and their preparation method and application, so as to partially solve or alleviate the above-mentioned deficiencies in the prior art. The present invention specifically adopts the following technical solutions.

[0006] The first aspect of the present invention is to provide sialoglycan-dexamethasone (PSA-Dex) polymer nanoparticles and a preparation method thereof.

[0007] A sialoglycan-dexamethasone polymer nanoparticle for treating inflammatory reactions caused by corneal burns, wherein the sialoglycan-dexamethasone polymer nanoparticle is formed by self-assembly of sialoglycan-dexamethasone polymers; the structural formula of the sialoglycan-dexamethasone polymer is shown in the compound of formula (1): Formula (I); In the compound of formula (I), sialoglycan and amino-modified dexamethasone are linked via an acid-sensitive hydrazone bond.

[0008] In the compound of formula (I), n=8-400.

[0009] Furthermore, the particle size of the sialoglycan-dexamethasone polymer nanoparticles is in the range of 50-200 nm.

[0010] Preferably, the particle size of the sialoglycan-dexamethasone polymer nanoparticles is about 100 nm.

[0011] The preparation method of the above-mentioned sialoglycan-dexamethasone polymer nanoparticles comprises the following steps: S01: condensation reaction of hydrazine hydrate and dexamethasone to obtain amino-modified dexamethasone Dex-NH2; S02: Activate the carboxyl group of polysialic acid, then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-carboxysuccinimide, stir and react at room temperature, then add Dex-NH2 and stir to obtain sialoglycan-dexamethasone polymer through amidation reaction; wherein, sialoglycan and amino-modified dexamethasone are linked through an acid-sensitive hydrazone bond; S03: dissolving the sialoglycan-dexamethasone polymer in methanol to obtain a sialoglycan-dexamethasone polymer methanol solution, and using a thin film dispersion method to allow the sialoglycan-dexamethasone polymer to self-assemble to form the sialoglycan-dexamethasone polymer nanoparticles.

[0012] Furthermore, after the dexamethasone in S01 is dissolved in methanol, the mixture is stirred and reacted at a high temperature in a molar ratio of hydrazine group in hydrazine hydrate to carbonyl group in dexamethasone of 1:5 to obtain Dex-NH2.

[0013] Furthermore, the mass ratio of the polysialic acid to the amino-modified dexamethasone in S02 is 0.5-2:1.

[0014] Furthermore, the mass ratio of the polysialic acid to the amino-modified dexamethasone in S02 includes 0.5:1, 1:1, 1.5:1 or 2:1.

[0015] Preferably, the mass ratio of the polysialic acid to the amino-modified dexamethasone in S02 is 1.5:1.

[0016] Furthermore, the sialoglycan-dexamethasone polymer methanol solution in S03 is rotated under vacuum until the methanol is completely evaporated to obtain the sialoglycan-dexamethasone polymer nanoparticles.

[0017] Another aspect of the present invention provides the use of sialoglycan-dexamethasone (PSA-Dex) polymer nanoparticles.

[0018] Application of the sialoglycan-dexamethasone polymer nanoparticles in the preparation of a drug for treating inflammation caused by corneal burns.

[0019] Furthermore, the corneal burn includes corneal acid burn and corneal alkali burn.

[0020] Furthermore, the dosage form of the drug includes eye drops or irrigation solutions.

[0021] Beneficial technical effects: The present invention first prepares amino-modified dexamethasone Dex-NH2, then chemically links polysialic acid PSA to Dex-NH2 via an acid-sensitive hydrazone bond to obtain the amphiphilic polymer PSA-Dex. PSA-Dex has a hydrophilic PSA backbone and hydrophobic Dex, and has the ability to self-assemble into nanoparticles in water. The present invention further prepares polysialic acid-dexamethasone nanoparticles (PDNPs) via a thin film dispersion method. The PDNPs prepared by this thin film dispersion method have uniform morphology and stable properties. Experiments have demonstrated that they can maintain good stability under long-term storage conditions. Furthermore, animal experiments have demonstrated that the PDNPs prepared by the present invention have good sustained-release properties, which can prolong their retention time in the eye, thereby achieving enhanced anti-inflammatory effects and promoting corneal repair.

[0022] In addition, since the sialopolysaccharide-dexamethasone polymer synthesized by the present invention has an acid-sensitive hydrazone bond, it can responsively release the Dex drug in a weakly acidic ocular environment (but will not release the drug rapidly under normal physiological conditions), thereby achieving responsive (acid-responsive), accurate, and targeted delivery of the drug (PSA can target Siglec-E receptors on the surface of macrophages and specifically bind to them), as well as enhancing the corneal penetration of the drug. It can also achieve rapid release of locally delivered nanoparticles and achieve an effective therapeutic concentration of Dex, thereby enhancing the anti-inflammatory effect and promoting corneal repair.

[0023] Finally, the synthesis method of the present invention can control the drug loading of Dex by adjusting the feeding amount of PSA and Dex-NH2, which can achieve the synthesis of nanoparticles with high drug loading or low drug loading, thereby meeting different clinical treatment needs. Therefore, the PDNPs of the present invention have great potential for clinical application. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following is a brief introduction to the drawings required for the embodiments or the description of the prior art. In all drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the various elements or parts are not necessarily drawn according to the actual scale. Obviously, the drawings described below are some embodiments of the present invention. For those of ordinary skill in the art, other drawings can also be obtained based on these drawings without inventive work.

[0025] Figure 1 Dex and Dex-NH2 in one embodiment of the present invention 1 H-NMR diagram (a is Dex 1 H-NMR diagram; b is Dex-NH2 1 H-NMR spectrum); Figure 2 The PSA-Dex synthesized in one embodiment of the present invention 1 H-NMR spectrum; Figure 3 Figure 1 is a particle size distribution diagram of PDNPs synthesized in one embodiment of the present invention; Figure 4 is a scanning electron micrograph of PDNPs synthesized in one embodiment of the present invention (scale bar is 100 nm); Figure 5 This is the result of investigating the in vitro storage stability of PDNPs in one of the embodiments of the present invention; Figure 6 This is the result of investigating the acid sensitivity of PDNPs in one of the embodiments of the present invention; Figure 7 This is a graph showing the in vitro release results of PDNPs in one of the embodiments of the present invention; Figure 8 This is one of the examples of the present invention to investigate the cell viability of PDNPs at different concentrations; Figure 9 In one of the embodiments of the present invention, the retention time of PDNPs in mouse eyes was investigated. DETAILED DESCRIPTION

[0026] To make the purpose, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0027] As used herein, "and / or" includes any and all combinations of one or more of the associated listed items.

[0028] Herein, "plurality" means two or more than two, ie, it includes two, three, four, five, etc.

[0029] As used in this specification, the term "about" typically means + / - 5% of the stated value, more typically + / - 4% of the stated value, more typically + / - 3% of the stated value, more typically + / - 2% of the stated value, even more typically + / - 1% of the stated value, and even more typically + / - 0.5% of the stated value.

[0030] In this specification, certain embodiments may be disclosed in a format that is within a range. It should be understood that this description of "within a range" is merely for convenience and brevity and should not be interpreted as a rigid limitation on the disclosed range. Therefore, the description of a range should be considered to have specifically disclosed all possible subranges and individual numerical values ​​within this range. For example, the description of a range of 1-6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within this range, such as 1, 2, 3, 4, 5, and 6. Regardless of the breadth of the range, the above rules apply.

[0031] Example 1 This example provides a method for synthesizing and characterizing PSA-Dex polymer nanoparticles.

[0032] (1) Synthesis of Dex-NH2.

[0033] During the chemical synthesis process, Dex-NH2 is produced by a condensation reaction between hydrazine hydrate and Dex. 520 mg of Dex is weighed on an electronic balance using weighing paper and transferred to a round-bottom flask equipped with a magnetic stirrer. 30 mL of methanol is then added to the flask to dissolve the product, which is then placed in an ultrasonicator until completely dissolved. Subsequently, 3 mL of hydrazine hydrate is added to the solution, with a molar ratio of 1:5 between the hydrazine group and the Dex carbonyl group. The round-bottom flask is placed in a heat-collecting, constant-temperature magnetic stirrer and heated at 80°C for 5 hours before collecting the product. During stirring, 500 µL of glacial acetic acid is added to create an acidic environment. After heating, an activated 500 kDa dialysis bag is removed and rinsed twice with ddH2O. One end of the bag is sealed with a sealing clip. The reaction mixture is then poured into the bag and the other end is sealed. The dialysis bag was placed in a beaker containing 5L of ddH2O and dialyzed for 48 hours using a stirrer. After dialysis, the sample was collected in a 50 mL beaker and placed in a -20°C refrigerator overnight. Subsequently, the pre-dried sample was placed in a freeze dryer for drying to obtain a white powder product. Finally, the product was analyzed by nuclear magnetic resonance (NMR) 1 The chemical structure of the obtained product was characterized by HNMR (see Figure 1 .

[0034] (2) Synthesis of PSA-Dex.

[0035] Polysialic acid (PSA) and Dex can be subjected to an amidation reaction to obtain PSA-Dex. The apparent molecular weight of the polysialic acid used in this example is 6W.

[0036] First, the carboxyl group of PSA needs to be activated. Weigh 150 mg of PSA with weighing paper on an electronic balance and transfer it to a flask with a magnetic stirrer. Then, add 20 mL of ddH2O to the flask to dissolve polysialic acid, and add 630 mg of 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI·HCL) and 378 mg of N-carboxylsuccinimide (NHS) to it, and then stir at room temperature for 2 hours. After stirring, weigh 100 mg of Dex-NH2 and dissolve it in DMSO, pour it into a beaker, and continue stirring at room temperature for 24 hours. After the reaction is completed, the reaction mixture is transferred to a dialysis bag with a molecular weight of 8000-12000 and dialyzed for 3 days. The dialyzed sample liquid is collected and freeze-dried to obtain a light yellow solid product. Finally, the same method is used 1 The chemical structure of the obtained product was characterized by HNMR technique. Figure 2 The chemical structure of the synthesized product PSA-Dex is shown in formula (I).

[0037] Formula (I).

[0038] (3) Preparation of PSA-Dex nanoparticles (PDNPs).

[0039] Use the thin film dispersion method to carry out the self-assembly reaction of PDNPs. Use an electronic balance to weigh 4 mg of the previously prepared PSA-Dex and pour it into a 50 mL round-bottom flask. Add 8 mL of methanol to dissolve it and place it in a sonicator until it is completely dissolved. Assemble the round-bottom flask on a rotary evaporator, turn on the circulating water multi-purpose vacuum pump, close the air hole, and rotate at 45 ℃ / 50 ℃ and a speed of 70-80 rpm until the methanol is completely evaporated, and a thin film will form at the bottom of the flask. Subsequently, add 2 mL of ddH2O for hydration reaction, place it in 50 ℃ water and shake it clockwise until it dissolves, and the assembled PDNPs solution is obtained. Finally, filter it into a centrifuge tube with a sterile filter head with a pore size of 0.22 μm and store it at 4 ℃. Figure 3 As shown in Figure 2, the particle size range of the nanoparticles is approximately 50-200 nm; the average particle size distribution is around 100 nm. In addition, as shown in Figure 2 Figure 4 As shown in Figure 3, under TEM, it can be observed that the prepared PDNPs present a uniform spherical structure.

[0040] By adjusting the feed ratio of PSA and Dex-NH2, PSA-Dex nanoparticles with different Dex loading amounts can be obtained, as shown in Table 1.

[0041] Table 1 PSA-Dex nanoparticles with different drug loadings can meet the requirements for local drug concentration under different clinical needs.

[0042] Example 2 This example provides performance verification of PSA-Dex nanoparticles (PDNPs).

[0043] (1) Stability test The stability of the PDNPs preparation was evaluated by placing the sample solution in a 4°C refrigerator for one week and observing the change in its particle size. The prepared PDNPs preparation was stored in a 4°C refrigerator, and the particle size of the PDNPs preparation was detected and recorded at the same time point on days 1, 3, 5, and 7.

[0044] The results are as follows Figure 5After one week at 4°C, the particle size of the formulation remained approximately 100 nm, and the polymer dispersity index (PDI) remained unchanged and remained below 0.3. These results indicate that the average particle size and PDI of PDNPs remained nearly unchanged after one week, demonstrating that the PDNP formulation exhibited good stability under long-term storage conditions.

[0045] (2) Acid sensitivity test Weigh 4 mg of the prepared PSA-Dex using an electronic balance and pour it into a 50 mL round-bottom flask. Add 8 mL of methanol to dissolve it, and place it in an ultrasonicator until it is completely dissolved. Assemble the round-bottom flask on a rotary evaporator, turn on the circulating water multi-purpose vacuum pump, close the air hole, and rotate at 45 ℃ / 50 ℃ and a speed of 70-80 rpm until the methanol is completely evaporated, and a thin film will form at the bottom of the flask. Subsequently, add 2 mL of PBS buffer solution with a pH value of 5.5 and 6.4 for hydration reaction, place it in 50 ℃ water and shake clockwise until it is completely dissolved. Finally, the particle size of the PDNPs solution was tested at 0, 2, 4 and 6 hours, and the results are shown in the table. Figure 6 .

[0046] The hydrazone bond formed between PSA and Dex is acid-sensitive. In an acidic environment, the hydrazone bond breaks, releasing Dex. The particle size distribution of PDNPs in PBS with pH values ​​of 6.5 and 5.5 was measured using a particle size analyzer to investigate the responsiveness of PDNPs in an acidic environment. As shown in the figure, the particle size of PDNPs at 0h was basically uniformly distributed around 100nm. However, after PDNPs were incubated in PBS with pH values ​​of 6.5 and 5.5 for 2h, the particle size distribution range was significantly expanded, indicating that PDNPs are highly sensitive to acidic environments. This phenomenon indicates that under acidic conditions, the destruction of the hydrazone bond causes Dex to separate from PSA, resulting in the release of Dex.

[0047] (3) In vitro release experiment To investigate the effect of an acidic environment on the release of Dex from PDNPs, dialysis was used in this example to analyze the release characteristics of PDNPs. An appropriate amount of PSA-Dex was placed in a round-bottom flask and PDNPs were prepared using a thin-film dispersion method. The total Dex concentration was determined to be 500 µg / mL. One mL of the prepared sample was added to a 10 kDa dialysis bag, which was sealed and placed in a glass vial containing 20 mL of release medium. The release medium consisted of phosphate buffer (containing 1% propylene glycol) at pH values ​​of 7.4, 6.5, and 5.5, respectively. Four replicates were prepared for each experimental group. A free Dex solution of the same concentration was also prepared as a control group and the same experimental procedures were followed. All samples were placed in a constant temperature shaking incubator set at 70 rpm and 37°C. At predetermined time points, 200 µL of the release solution was removed from each sample and supplemented with an equal volume of the corresponding release medium. After 24 hours, all samples were sampled and filtered with a 0.22 µm filter head. The Dex content in the released samples was then determined using high performance liquid chromatography. Based on the measurement results, the cumulative release rate of Dex under different conditions was calculated, and the release curve was drawn to analyze the release behavior of Dex. The results are shown in Figure 7 .

[0048] The results showed that PDNPs did not rapidly release the drug under normal physiological conditions. However, when the PDNPs were placed in an acidic PBS solution (pH 5.5), the drug release percentage increased to 33% within 1 hour. The drug release rate gradually increased over time, reaching 60% at 24 hours. These results indicate that acidic conditions promote the release of Dex from PDNPs, demonstrating the potential for responsive Dex release in inflammatory settings.

[0049] (4) Cytotoxicity experiment Cell plating: Observe the status of HCE-T, RAW264.7, and HUVEC cells under a microscope. Passage cells when they are in good condition and have reached 80%-90% confluency. Aspirate the HCE-T cell-specific culture medium and DMEM high-glucose complete culture medium containing metabolites. Wash the cells twice with 3 mL of sterile 1× PBS buffer, shaking. The 1× PBS should be added against the wall of the dish, and the pipette tip should not touch the wall. After discarding the 1× PBS, add 1 mL of 0.25% trypsin containing EDTA to the dish to digest the cells. Incubate at room temperature for 1 minute. Terminate digestion when cells appear bright and round under a microscope. (Since trypsin can affect the polarization of RAW264.7 cells, the trypsinization step is not required.) Aspirate the trypsin and terminate digestion by adding 2 mL of complete culture medium. Mix thoroughly by pipetting. Aspirate the cell suspension into a 15 mL centrifuge tube and centrifuge at 1000 rpm for 3 minutes. Discard the supernatant. After resuspending in 1 mL of culture medium, transfer 20 μL of the cell suspension to a dedicated counting plate. Count the cells using an automated cell analyzer and seed approximately 8,000 cells in a 96-well plate. Add 200 μL of PBS phosphate buffer to the outermost wells and incubate overnight in an incubator.

[0050] Drug treatment: 1 mg / mL PDNPs, 100 μg / mL Dex, and 1 mg / mL PSA were prepared using HCE-T cell-specific culture medium and DMEM high-glucose complete medium. The original culture medium was aspirated and 100 μL of drug was added to each well for 12 and 24 hours.

[0051] CCK8 incubation and determination: After 12 and 24 hours of culture, a working solution was prepared using HCE-T cell culture medium and DMEM high-glucose complete culture medium at a ratio of CCK8: culture medium = 1:9. After discarding the original well drug, 100 μL of the prepared working solution was added to each well and incubated in a cell culture incubator for 2 hours. Then, the absorbance value at 450 nm was measured using a microplate reader, and the cell survival rate was calculated. The results are shown in Figure 8 The results showed that PDNPs have good biosafety.

[0052] (5) In vivo imaging of mice Mice were randomly divided into two groups: a free Did (fluorescent dye) group and a PDNPs-Did group. Subsequently, an anesthetic was injected intraperitoneally into the mice. After anesthesia, 10 μL of Did solution and 10 μL of PDNPs-Did solution were dripped onto the ocular surface of the experimental mice using a pipette. Fluorescence signals were then detected using an in vivo fluorescence imaging system at 30 s, 2 min, 5 min, 10 min, 30 min, and 1 h. The results are shown in Figure 2. Figure 9 .

[0053] The results showed that the retention time of PDNPs in the mouse eyes was significantly increased compared with the free group.

[0054] The embodiments of the present invention are described above in conjunction with the accompanying drawings, but the present invention is not limited to the above-mentioned specific implementation methods. The above-mentioned specific implementation methods are merely illustrative and not restrictive. Under the guidance of the present invention, ordinary technicians in this field can also make many forms without departing from the scope of protection of the present invention and the claims, all of which are protected by the present invention.

Claims

1. A sialoglycoside-dexamethasone polymer nanoparticle for treating inflammatory reactions caused by corneal burns, characterized in that: The sialoglycoside-dexamethasone polymer nanoparticles are formed by self-assembly of sialoglycoside-dexamethasone polymers; the structural formula of the sialoglycoside-dexamethasone polymer is shown in formula (1): Formula (I); In the compound of formula (I), sialoglycan and amino-modified dexamethasone are linked via an acid-sensitive hydrazone bond.

2. The sialoglycan-dexamethasone polymer nanoparticles according to claim 1, wherein The particle size of the sialoglycan-dexamethasone polymer nanoparticles ranges from 50 to 200 nm.

3. The method for preparing sialoglycan-dexamethasone polymer nanoparticles according to claim 1, characterized in that: The following steps are involved: S01: condensation reaction of hydrazine hydrate and dexamethasone to obtain amino-modified dexamethasone Dex-NH2; S02: Activate the carboxyl group of polysialic acid, then add 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride and N-carboxysuccinimide, stir and react at room temperature, then add Dex-NH2 and stir to obtain sialoglycan-dexamethasone polymer through amidation reaction; wherein, sialoglycan and amino-modified dexamethasone are linked through an acid-sensitive hydrazone bond; S03: dissolving the sialoglycan-dexamethasone polymer in methanol to obtain a sialoglycan-dexamethasone polymer methanol solution, and using a thin film dispersion method to allow the sialoglycan-dexamethasone polymer to self-assemble to form the sialoglycan-dexamethasone polymer nanoparticles.

4. The preparation method according to claim 3, wherein After the dexamethasone described in S01 is dissolved in methanol, the mixture is stirred and reacted at high temperature in a molar ratio of hydrazine group in hydrazine hydrate to carbonyl group in dexamethasone of 1:5 to obtain Dex-NH2.

5. The preparation method according to claim 3, wherein The mass ratio of the polysialic acid to the amino-modified dexamethasone in S02 is 0.5-2:

1.

6. The preparation method according to claim 5, wherein The mass ratio of the polysialic acid to the amino-modified dexamethasone in S02 includes 0.5:1, 1:1, 1.5:1 or 2:

1.

7. The preparation method according to claim 3, wherein The sialoglycan-dexamethasone polymer methanol solution in S03 is rotated under vacuum until the methanol is completely evaporated to obtain the sialoglycan-dexamethasone polymer nanoparticles.

8. Use of the sialoglycan-dexamethasone polymer nanoparticles according to claim 1 or the sialoglycan-dexamethasone polymer nanoparticles according to any one of claims 3 to 7 in the preparation of a medicament for treating inflammation caused by corneal burns.

9. The use according to claim 8, characterized in that The corneal burns include corneal acid burns and corneal alkali burns.

10. The use according to claim 8, characterized in that The dosage form of the drug includes eye drops or irrigation solutions.

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