Arthrophlogosis treatment system based on PLGA nanoparticles with different morphologies and preparation method

Abstract

The invention discloses an arthritis treatment system based on PLGA (poly (lactic-co-glycolic acid)) nano-particles with different morphologies and a preparation method. The arthritis treatment system comprises rod-shaped drug-loaded PLGA nano-particles and disc-shaped PLGA nano-particles modified by N-acetylneuraminic acid, the preparation method comprises the following steps: respectively preparing rod-like drug-loaded PLGA (poly (lactic-co-glycolic acid)) nano-particles and disc-like PLGA nano-particles modified by N-acetylneuraminic acid; and mixing the PLGA nano-particles with the PLGA nano-particles to obtain the arthritis treatment system based on the PLGA nano-particles with different morphologies. The invention can overcome the defects of low bioavailability and large toxic and side effects on an immune system of clinically used rheumatoid arthritis drugs, and provides a rheumatoid arthritis treatment system which can block neutrophil inflammation recruitment and does not influence the activity of neutrophil.

Description

Technical Field

[0001] The present invention relates to the technical field of arthritis therapeutic drugs, and in particular to an arthritis therapeutic system based on PLGA nanoparticles with different morphologies and a preparation method thereof. Background Art

[0002] Rheumatoid arthritis is a chronic autoimmune disease accompanied by degenerative joint damage, affecting approximately 1% of the world's population. When it develops, it usually leads to destruction of articular cartilage and erosion of surrounding bones, ultimately damaging the integrity and motor function of the joints, and seriously affecting the patient's quality of life. At present, the clinical pathogenesis of rheumatoid arthritis is not yet fully understood, so a large number of patients are difficult to diagnose in the early stages and miss the best time for treatment. In addition, drugs commonly used to treat rheumatoid arthritis, such as glucocorticoids, non-steroidal anti-inflammatory drugs, and relief drugs specifically for this condition, are currently unable to achieve a cure for the disease. Moreover, most of these drugs face problems such as short half-life and insufficient targeting, and the resulting toxic side effects on the immune system and major organs cannot be ignored.

[0003] During the development of rheumatoid arthritis, immune cells infiltrate the lumenal joint space, leading to increased inflammation and tissue damage. Current treatments for overactive immune cells primarily inhibit specific inflammatory cytokines and their associated pathways, or reduce the number of immune cell responses through apoptosis induction. These approaches may disrupt the cytokine balance in the body and produce adverse side effects on the immune system. Summary of the Invention

[0004] In response to the above problems, the present invention aims to provide an arthritis treatment system based on PLGA nanoparticles with different morphologies and a preparation method.

[0005] The technical solutions of the present invention are as follows: On the one hand, an arthritis treatment system based on PLGA nanoparticles with different morphologies is provided, including rod-shaped drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles.

[0006] Preferably, the drug loaded in the drug-loaded PLGA nanoparticles is piceatannol.

[0007] Preferably, the mass ratio of the drug loaded in the drug-loaded PLGA nanoparticles to the PLGA nanoparticles is 1:7.5-12.

[0008] Preferably, the mass ratio of the rod-shaped drug-loaded PLGA nanoparticles to the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles is 1:0.75-1.

[0009] Preferably, the rod-shaped drug-loaded PLGA nanoparticles and the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles are prepared by the following steps: S1: A solvent-antisolvent evaporation method was used to prepare a concentrate of spherical drug-loaded PLGA nanoparticles and a concentrate of spherical N-acetylneuraminic acid-modified PLGA nanoparticles; S2: mixing the concentrated solution of the spherical drug-loaded PLGA nanoparticles with the PVA aqueous solution and spreading the mixture in a rectangular mold, and drying the mixture to form a film; The concentrated solution of the spherical N-acetylneuraminic acid-modified PLGA nanoparticles is mixed with a PVA aqueous solution and spread in a circular mold, and dried to form a film; S3: applying tension to the rectangular film obtained in step S2 to stretch it, and applying pressure to the circular film obtained in step S2 to compress it, to obtain a deformed film; S4: dissolving the deformable film obtained in step S3 in a neutral pH buffer solution, dialyzing, and centrifuging to obtain the rod-shaped drug-loaded PLGA nanoparticles and the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles.

[0010] Preferably, in step S2, the concentration of the PVA aqueous solution is 15%, and the volume ratio of the mixed nanoparticles to the PVA aqueous solution is 1:1.8-2.2.

[0011] Preferably, in step S2, drying is performed at 35-40° C. for 4-6 hours.

[0012] Preferably, in step S3, when the stretching deformation is performed, the longitudinal deformation amount is 2-2.5 times; when the heavy pressure deformation is performed, the applied pressure is 20-40 MPa.

[0013] Preferably, in step S3, shaping specifically includes the following sub-steps: first heating at above 55°C for 0.5-1h, and then shaping at below 0°C for 1-2h.

[0014] On the other hand, a method for preparing any of the above-mentioned arthritis treatment systems based on PLGA nanoparticles with different morphologies is also provided, comprising the following steps: Rod-shaped drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles were prepared respectively; The drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles are mixed to obtain the arthritis treatment system based on PLGA nanoparticles with different morphologies.

[0015] The beneficial effects of the present invention are: The present invention can overcome the defects of low bioavailability and large toxic side effects on the immune system of clinically used rheumatoid arthritis drugs, and provide a rheumatoid arthritis treatment system that can block neutrophil inflammatory recruitment without affecting their activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0017] Figure 1 is a diagram of the preparation process of rod-shaped and disk-shaped nanoparticles in a specific embodiment; Figure 2 Transmission electron microscopy images of spherical, rod-shaped and disc-shaped nanoparticles in Example 1; Figure 3 Figure 1 is a graph showing the particle sizes of spherical, rod-shaped, and disc-shaped nanoparticles in Example 1; Figure 4 Flow cytometric images of blood leukocytes engulfing spherical or rod-shaped nanoparticles; Figure 5 Images of the hind feet of mice after treatment; Figure 6 Schematic diagram of the test results of ankle joint diameter and paw thickness of mice after treatment; Figure 7 This is the flow cytometric image of neutrophils in the joint cavity of mice after treatment; Figure 8 This is a statistical chart of inflammatory factors in mice after treatment. DETAILED DESCRIPTION

[0018] The present invention is further described below with reference to the accompanying drawings and examples. It should be noted that, in the absence of conflict, the embodiments in this application and the technical features in the embodiments can be combined with each other. It should be noted that, unless otherwise specified, all technical and scientific terms used in this application have the same meanings as those commonly understood by those of ordinary skill in the art to which this application belongs. The use of similar words such as "include" or "comprising" in the present invention means that the elements or objects appearing before the word cover the elements or objects listed after the word and their equivalents, without excluding other elements or objects.

[0019] On the one hand, the present invention provides an arthritis treatment system based on PLGA nanoparticles of different morphologies, including rod-shaped drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles.

[0020] In the present invention, the rod-shaped drug-loaded PLGA nanoparticles have a passive targeting ability of being preferentially phagocytosed by neutrophils, thereby being able to target neutrophils; the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles can produce adhesion to inflammatory endothelial cells through the N-acetylneuraminic acid modified on their surface, and further prevent neutrophil recruitment to the inflammatory site by adhering to the inflammatory endothelial cells; in summary, the present invention can block the inflammatory recruitment of neutrophils without affecting the activity of neutrophils.

[0021] Substances released by neutrophils, such as proinflammatory cytokines, reactive oxygen species (ROS), proteases, and neutrophil extracellular traps, can aggravate joint degeneration. They can also act as autoantigens in the immune process to promote self-recruitment, leading to explosive growth of immune cells. The present invention can better control rheumatoid arthritis by resisting the early recruitment of neutrophils.

[0022] In addition, the present invention uses poly(lactic acid-co-glycolic acid) (PLGA) as the main material of the drug carrier, which has the advantages of high biocompatibility, low toxicity of degradation products, excellent drug encapsulation efficiency and low cost.

[0023] In a specific embodiment, the drug loaded into the drug-loaded PLGA nanoparticles is piceatannol. In this embodiment, piceatannol loaded into the rod-shaped nanoparticles can inhibit the activation of β2-integrin by downregulating the neutrophil SYK pathway, thereby further delaying the recruitment of neutrophils to the inflammatory site.

[0024] In a specific embodiment, the mass ratio of the drug loaded in the drug-loaded PLGA nanoparticles to the PLGA nanoparticles is 1:10, and the mass ratio of the rod-shaped drug-loaded PLGA nanoparticles to the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles is 1:0.75-1.

[0025] In a specific embodiment, Figure 1 As shown, the rod-shaped drug-loaded PLGA nanoparticles and the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles are prepared by the following steps: S1: A solvent-antisolvent evaporation method was used to prepare a concentrate of spherical drug-loaded PLGA nanoparticles and a concentrate of spherical N-acetylneuraminic acid-modified PLGA nanoparticles; S2: mixing the concentrated solution of the spherical drug-loaded PLGA nanoparticles with the PVA aqueous solution and spreading the mixture in a rectangular mold, and drying the mixture to form a film; The concentrated solution of the spherical N-acetylneuraminic acid-modified PLGA nanoparticles is mixed with a PVA aqueous solution and spread in a circular mold, and dried to form a film; S3: applying tension to the rectangular film obtained in step S2 to stretch it, and applying pressure to the circular film obtained in step S2 to compress it, to obtain a deformed film; S4: dissolving the deformable film obtained in step S3 in a neutral pH buffer solution, dialyzing, and centrifuging to obtain the rod-shaped drug-loaded PLGA nanoparticles and the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles.

[0026] In the above embodiment, using a PVA aqueous solution as a carrier for film formation can facilitate subsequent deformation by utilizing the characteristics of PVA, and using water as a solvent can prevent the formed nanoparticles from being dissolved again.

[0027] In a specific embodiment, in step S2, the concentration of the PVA aqueous solution is 15%, and the volume ratio of the mixed nanoparticles to the PVA aqueous solution is 1:1.8-2.2.

[0028] In a specific embodiment, in step S2, drying is performed at 35-40°C for 4-6 hours; in step S3, shaping specifically includes the following sub-steps: first heating at above 55°C for 0.5-1 hour, and then shaping at below 0°C for 1-2 hours.

[0029] In a specific embodiment, in step S3, when the stretching deformation is performed, the longitudinal deformation amount is 2-2.5 times; when the heavy pressure deformation is performed, the applied pressure is 20-40 MPa.

[0030] It should be noted that the preparation method of the rod-shaped nanoparticles and disk-shaped nanoparticles in the above embodiment is only a preferred embodiment of the present invention. Rod-shaped nanoparticles and disk-shaped nanoparticles of the same shape prepared by other preparation methods have similar properties and are also applicable to the present invention.

[0031] On the other hand, the present invention also provides a method for preparing any of the above-mentioned arthritis treatment systems based on PLGA nanoparticles with different morphologies, comprising the following steps: Rod-shaped drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles were prepared respectively; The drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles are mixed to obtain the arthritis treatment system based on PLGA nanoparticles with different morphologies.

[0032] Example 1 An arthritis treatment system based on PLGA nanoparticles with different morphologies, including rod-shaped drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles.

[0033] The rod-shaped drug-loaded PLGA nanoparticles are prepared by the following steps: (1) PLGA nanoparticles (30 mg) and piceatannol (3 mg) were mixed and dissolved in 5 mL of acetone. The acetone solution was then slowly added dropwise to 30 mL of PBS solution at a uniform rate. The mixture was heated in a 35°C water bath and stirred for 2 h. The mixture was centrifuged and concentrated to obtain a spherical drug-loaded PLGA nanoparticle concentrated solution. (2) The spherical drug-loaded PLGA nanoparticle concentrated solution (1 mL) was mixed with a 15% PVA aqueous solution (2 mL), spread onto multiple rectangular molds of 80 mm × 30 mm × 2 mm, and dried at 35 °C for 6 h to form a film; (3) Fix the two ends of the rectangular film obtained in step (2) and slowly insert an iron sheet from the center outward to stretch the film. Heat the film at a temperature above 55°C for 0.5 h and then place the film below 0°C for 1 h. (4) The deformable film obtained in step (3) is dissolved in PBS and the solution is dialyzed and concentrated by centrifugation to obtain the rod-shaped drug-loaded PLGA nanoparticles.

[0034] The disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles are prepared by the following steps: (5) Dissolve N-acetylneuraminic acid-modified PLGA (60 mg) in 5 mL of acetone, then slowly add the acetone solution dropwise to 40 mL of PBS solution at a uniform speed. Stir in an open position under heating at 35 °C in a water bath for 2 h, and concentrate by centrifugation to obtain a concentrated solution of spherical N-acetylneuraminic acid-modified PLGA nanoparticles. (6) The spherical N-acetylneuraminic acid-modified PLGA nanoparticle concentrated solution (1 mL) was mixed with a 15% PVA aqueous solution (2 mL), spread on a circular mold with a diameter of 40 mm, and dried at 35°C for 6 h to form a film; (7) The circular film obtained in step (2) is sandwiched between two iron blocks and subjected to heavy pressure deformation by applying a pressure of 30 MPa using a hydraulic press, and then heated at above 55°C for 0.5 h, and then placed below 0°C for 1 h; (8) The deformable film obtained in step (3) is dissolved in PBS and the solution is dialyzed and concentrated by centrifugation to obtain the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles.

[0035] Test Example 1 The morphology of the spherical nanoparticles (the spherical nanoparticles prepared in step (1)), the rod-shaped drug-loaded PLGA nanoparticles, and the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles were observed using a transmission electron microscope and the particle size of each particle was measured. The results are as follows: Figure 2-3 As shown. Figure 2-3 It can be seen that rod-shaped nanoparticles and disc-shaped nanoparticles were successfully prepared in this example, and the particle size of the rod-shaped drug-loaded PLGA nanoparticles was 356.1 nm, and the particle size of the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles was 509 nm.

[0036] Test Example 2 The same steps as in Example 1 were used to replace piceatannol with an equal amount of rhodamine, and rhodamine-labeled rod-shaped nanoparticles were prepared in the same manner, and some spherical nanoparticles were retained in step (1) as a control experiment. Whole blood was obtained from mice by standardizing the mouse orbital blood collection operation, and spherical and rod-shaped nanoparticles labeled with equivalent rhodamine signals were added to the collected blood for 2 hours. The samples were then placed on ice and incubated with 2 mL of 1×RBC lysis buffer for 10 minutes, centrifuged at 500×g for 5 minutes, and the obtained cells were incubated with anti-CD45, anti-CD11b, and anti-Ly6G antibodies for 30 minutes. Different types of cells were screened out by flow cytometry testing and the competitive phagocytic ability of various phagocytes in the blood for rod-shaped nanoparticles was evaluated based on the positive cell ratio of the rhodamine channel. The results are as follows: Figure 4 shown.

[0037] from Figure 4 It can be seen that the phagocytic rate of rod-shaped nanoparticles by neutrophils is 49.9%, and the phagocytic rate of spherical nanoparticles by neutrophils is 17.8%. The phagocytic rate of rod-shaped nanoparticles is 2.80 times that of spherical nanoparticles. At the same time, the phagocytic rate of rod-shaped nanoparticles by macrophages is 8.79%, and the phagocytic rate of rod-shaped nanoparticles by neutrophils is 5.68 times that of macrophages.

[0038] Test Example 3 DBA / 1 mice were injected with 100 μL of type II collagen emulsion on days 0 and 21 to establish a CIA arthritis model. Starting 31 days after modeling, three groups of DBA / 1 mice were injected with 200 μL of saline, 200 μL of 0.25 mg / mL piceatannol in PBS, 200 μL of 10 mg / mL PLGA discoids, 200 μL of 0.25 mg / mL PLGA rodoids, or 200 μL of a mixed solution of 10 mg / mL PLGA and 0.25 mg / mL piceatannol via the tail vein every 3 days. A group of healthy mice, which were not injected with type II collagen adjuvant, were also included. These groups were designated as the control group, drug group, experimental group 1, experimental group 2, experimental group 3, and healthy group, respectively. Every 3 days after surgery, a vernier caliper was used to measure and record the ankle diameter and paw thickness of the mice to evaluate the development of rheumatoid arthritis. The images of the hind feet of the mice after treatment are as follows: Figure 5 As shown, the ankle joint diameter and claw thickness data are as follows Figure 6 As shown in Table 1: Table 1 Ankle joint diameter and claw thickness data

[0039] Note: The data in Table 1 are the average data of 5 mice.

[0040] from Figure 5 、 Figure 6 As can be seen from Table 1, the drug group did not produce significant therapeutic effects; although the two nanoparticles in experimental groups 1 and 2 produced certain therapeutic effects when used alone, the therapeutic effects were not good; the combination of the two nanoparticles in experimental group 3 had a better therapeutic effect, and the arthritis swelling in mice was significantly improved, proving that the therapeutic system of the present invention has a significant improvement effect on the symptoms of rheumatoid arthritis.

[0041] Test Example 4 Twenty-one days after treatment (52 days after modeling) in Test Example 3, cartilage from the quadruped joints of mice was removed. The cartilage was ground using a hand drill and digested with 0.5% trypsin for 60 minutes. The resulting single-cell suspension was then filtered through a 200-mesh cell filter and centrifuged at 500×g for 5 minutes. The resulting single-cell suspension was incubated with anti-Ly6G antibody at 4°C for 30 minutes. The proportion of neutrophils in the inflamed joints was measured by flow cytometry. The results were as follows: Figure 7 As shown. Figure 7It can be seen that the neutrophil reduction rate of the drug group in the single-cell suspension of the mid-articular cavity was 16.3%, the neutrophil reduction rates of experimental groups 1 and 2 using only PLGA nanoparticles of a certain morphology were 36.2% and 38.4%, respectively, while the neutrophil reduction rate of experimental group 3 of the present invention using PLGA nanoparticles of two morphologies at the same time reached 56.4%, proving that the therapeutic system of the present invention has a better neutrophil recruitment inhibitory effect.

[0042] Test Example 5 For the mice in Test Example 3 21 days after treatment (52 days after modeling), blood was collected from the experimental mice into non-anticoagulant tubes by eye sampling and serum separation was performed. The ELISA kit was used and samples were prepared according to the operating instructions. The OD450 standard curves of inflammatory factors TNF-α, IL17, and IFN-γ were measured and drawn using a UV spectrophotometer. At the same time, blood samples from each group of mice were measured and the expression levels of inflammatory factors were calculated according to the standard curves to evaluate the alleviating effect of the inflammatory response under the action of the present invention. The results are as follows: Figure 8 As shown. Figure 8 It can be seen that the expression levels of TNF-α, IL17, and IFN-γ in the drug group were downregulated by 20.8%, 13.2%, and 33.2%, respectively; the expression levels of TNF-α, IL17, and IFN-γ in experimental group 1 were downregulated by 41.3%, 20.8%, and 44.0%, respectively; the expression levels of TNF-α, IL17, and IFN-γ in experimental group 2 were downregulated by 45.6%, 31.2%, and 50.7%, respectively; the expression levels of TNF-α, IL17, and IFN-γ in experimental group 3 of the present invention were downregulated by 59.7%, 44.1%, and 62.1%, respectively, demonstrating that the therapeutic system of the present invention has a better inhibitory effect on inflammatory factors.

[0043] It should be noted that the above test examples are only partial test results of the embodiments of the present invention. The other embodiments have similar effects to Example 1, and all can block the inflammatory recruitment of neutrophils without affecting their activity. In addition, the above examples are only partial embodiments of the present invention. The therapeutic system composed of rod-shaped drug-loaded PLGA nanoparticles and the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles obtained by changing the preparation method parameters and using other preparation methods all have similar effects.

[0044] In summary, the present invention provides an arthritis treatment system that blocks neutrophil recruitment without affecting their activity, which represents a significant improvement over existing technologies.

[0045] The above description is merely a representative embodiment of the present invention and does not constitute any form of limitation to the present invention. Any technical personnel familiar with the present invention who, without departing from the scope of the technical solution of the present invention, makes slight changes or modifications to the embodiments disclosed above using the technical contents disclosed above are equivalent embodiments of the present invention. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. An arthritis treatment system based on PLGA nanoparticles with different morphologies, characterized in that: It includes rod-shaped drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles.

2. The arthritis treatment system based on PLGA nanoparticles with different morphologies according to claim 1, characterized in that: The drug loaded in the drug-loaded PLGA nanoparticles is piceatannol.

3. The arthritis treatment system based on PLGA nanoparticles with different morphologies according to claim 1 or 2, characterized in that: The mass ratio of the drug loaded in the drug-loaded PLGA nanoparticles to the PLGA nanoparticles is 1:7.5-12.

4. The arthritis treatment system based on PLGA nanoparticles with different morphologies according to claim 1, characterized in that: The mass ratio of the rod-shaped drug-loaded PLGA nanoparticles to the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles is 1:0.75-1.

5. The arthritis treatment system based on PLGA nanoparticles with different morphologies according to any one of claims 1 to 4, characterized in that: The rod-shaped drug-loaded PLGA nanoparticles and the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles are prepared by the following steps: S1: A solvent-antisolvent evaporation method was used to prepare a concentrate of spherical drug-loaded PLGA nanoparticles and a concentrate of spherical N-acetylneuraminic acid-modified PLGA nanoparticles; S2: mixing the concentrated solution of the spherical drug-loaded PLGA nanoparticles with the PVA aqueous solution and spreading the mixture in a rectangular mold, and drying the mixture to form a film; The concentrated solution of the spherical N-acetylneuraminic acid-modified PLGA nanoparticles is mixed with a PVA aqueous solution and spread in a circular mold, and dried to form a film; S3: applying tension to the rectangular film obtained in step S2 to stretch it, and applying pressure to the circular film obtained in step S2 to compress it, to obtain a deformed film; S4: dissolving the deformable film obtained in step S3 in a neutral pH buffer solution, dialyzing, and centrifuging to obtain the rod-shaped drug-loaded PLGA nanoparticles and the disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles.

6. The arthritis treatment system based on PLGA nanoparticles with different morphologies according to claim 5, characterized in that: In step S2, the concentration of the PVA aqueous solution is 15%, and the volume ratio of the mixed nanoparticles to the PVA aqueous solution is 1:1.8-2.

2.

7. The arthritis treatment system based on PLGA nanoparticles with different morphologies according to claim 5, characterized in that: In step S2, drying is performed at 35-40° C. for 4-6 hours.

8. The arthritis treatment system based on PLGA nanoparticles with different morphologies according to claim 5, characterized in that: In step S3, when the stretching deformation is performed, the longitudinal deformation amount is 2-2.5 times; when the heavy pressure deformation is performed, the applied pressure is 20-40 MPa.

9. The arthritis treatment system based on PLGA nanoparticles with different morphologies according to claim 5, characterized in that: In step S3, shaping specifically includes the following sub-steps: first heating at above 55° C. for 0.5-1 h, and then shaping at below 0° C. for 1-2 h.

10. The method for preparing an arthritis treatment system based on PLGA nanoparticles with different morphologies according to any one of claims 1 to 9, characterized in that: The following steps are involved: Rod-shaped drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles were prepared respectively; The drug-loaded PLGA nanoparticles and disc-shaped N-acetylneuraminic acid-modified PLGA nanoparticles are mixed to obtain the arthritis treatment system based on PLGA nanoparticles with different morphologies.

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