Stm2457-plga nanodrug, intraocular lens and preparation method and application thereof

Abstract

The application discloses an STM2457-PLGA nano drug, an artificial lens and a preparation method and application thereof, and relates to the technical field of biological medicine. The preparation method of the STM2457-PLGA nano drug comprises the following steps: preparing nano microspheres by injecting an oil phase comprising STM2457 and PLGA and a water phase comprising PVA into a microfluidic chip, and obtaining the STM2457-PLGA nano drug after freeze-drying of the nano microspheres, wherein the particle size of the STM2457-PLGA nano drug is 50-300 nm. The long-acting release of STM2457 carried by the surface-modified artificial lens is realized through the controlled release effect of the PLGA nano microspheres, and the slow-release period can cover the high-incidence period of postoperative complications of cataract surgery through process optimization, far exceeding the traditional short-term release system, and can continuously meet the long-term prevention and treatment needs after surgery, and effectively reduce the risk of complications such as after-cataract.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and in particular to an STM2457-PLGA nanomedicine, an intraocular lens, its preparation method, and its application. Background Technology

[0002] In recent years, with the development of biomaterial modification technology, research on various functionalized intraocular lenses (IOLs) for the prevention and treatment of posterior cataract (PCO) has been continuously advancing and has achieved phased progress. The core need for treating PCO at present is to inhibit the proliferation, migration, and epithelial-mesenchymal transition (EMT) process of residual lens epithelial cells (LECs) after cataract surgery.

[0003] Although routine intraocular lens implantation can restore immediate vision, residual LECs after surgery are prone to proliferate and fibrosis within the lens capsule, eventually leading to re-obscuring of the visual axis. The incidence rate in adults is 20%-40% within two years after surgery, while in children, due to the stronger proliferative activity of LECs and the vigorous regeneration capacity of the lens, the incidence rate is nearly 100%. For peripheral eye diseases (PCO) that severely affect vision, yttrium-aluminum-garnet (YAG) laser capsulotomy is the primary clinical intervention. However, this procedure is not without risks and may cause a series of serious complications, such as temporary increase in intraocular pressure, lens subluxation / dislocation, retinal detachment, and exacerbation of local endophthalmitis. More importantly, in developing countries and regions with scarce medical resources and limited economic conditions, a large number of PCO patients cannot obtain timely and standardized laser or surgical treatment. This issue has become a public health challenge that urgently needs to be addressed in the global ophthalmological medical field. Traditional postoperative adjuvant therapies, such as corticosteroid eye drops and intravitreal injections of antimetabolites, have problems such as poor targeting, significant systemic side effects, and low patient compliance. Moreover, the drugs cannot accurately target residual lens capsular structures (LECs) within the capsular bag, resulting in limited treatment efficacy.

[0004] In addition, existing drug-loaded intraocular lenses still have drawbacks such as low drug loading, premature drug release, and short sustained-release period, which cannot achieve long-term effective prevention of postoperative pulmonary embolism (PCO). Summary of the Invention

[0005] To address the technical problems existing in the prior art, this invention provides an STM2457-PLGA nanomedicine, an intraocular lens, its preparation method, and its application. The technical solution is as follows:

[0006] An STM2457-PLGA nanomedicine, the preparation method of which includes: preparing nanospheres by injecting an oil phase including STM2457 and PLGA and an aqueous phase including PVA into a microfluidic chip, and freeze-drying the nanospheres to obtain the STM2457-PLGA nanomedicine, wherein the particle size of the STM2457-PLGA nanomedicine is 50-300 nm.

[0007] The preparation method of the STM2457-PLGA nanomedicine includes:

[0008] (1) Preparation of oil phase solution: STM2457 and PLGA are dissolved in an organic solvent;

[0009] (2) Preparation of aqueous solution: Prepare PVA aqueous solution;

[0010] (3) Microfluidic synthesis of nanospheres: The oil phase solution and the aqueous phase solution are injected into a microfluidic chip to form an oil-in-water emulsion, and the effluent is collected;

[0011] (4) Curing: The effluent from step (3) is cured by solvent evaporation and freeze-dried to obtain the STM2457-PLGA nanomedicine.

[0012] Optionally, in step (1), the concentration of the STM2457 is 0.5-1.5 mg / ml, and / or the concentration of the PLGA is 4-6 mg / ml;

[0013] And / or, in step (1), the concentration of the STM2457 is 1 mg / ml, and / or, the concentration of the PLGA is 5 mg / ml;

[0014] And / or, in step (2), the mass concentration of the PVA aqueous solution is 1-3%;

[0015] And / or, in step (2), the mass concentration of the PVA aqueous solution is 2%;

[0016] And / or, in step (3), the volume ratio of the oil phase solution to the aqueous phase solution is (1-3):(5-7);

[0017] And / or, in step (3), the volume ratio of the oil phase solution to the aqueous phase solution is 2:6;

[0018] And / or, in step (4), the freeze-drying conditions are: -40 to -60°C, 9-15 h;

[0019] And / or, in step (4), the freeze-drying conditions are: -50°C, 12h.

[0020] An intraocular lens for treating posterior cataracts, wherein the non-optical region of the intraocular lens is coated with a drug-loaded sustained-release coating, the drug-loaded sustained-release coating comprising: the STM2457-PLGA nanomedicine.

[0021] Optionally, the non-optical region includes the edge of the optical region of the plate-shaped intraocular lens and / or the haptic of the intraocular lens;

[0022] And / or, the drug-loaded sustained-release coating has a ring structure.

[0023] The method for preparing the artificial lens includes the following steps:

[0024] (1) Pretreatment of intraocular lens: Disinfect the intraocular lens;

[0025] (2) Preparation of spin coating solution: The STM2457-PLGA nanomedicine is dispersed in PVA aqueous solution to obtain spin coating solution;

[0026] (3) Preparation of ring coating: The spin coating liquid from step (2) is added to the non-optical area of ​​the intraocular lens from step (1) and spin coated to form the drug-loaded sustained-release coating;

[0027] (4) Curing: The artificial lens obtained in step (3) is dried and cured to obtain the artificial lens.

[0028] Optionally, in step (1), the intraocular lens is a hydrophobic acrylate intraocular lens;

[0029] And / or, in step (2), the spin coating solution further includes: 0.5% PEG, wherein the molecular weight of the PEG is 2000;

[0030] And / or, in step (2), the concentration of STM2457-PLGA nanomedicine in the spin coating solution is 0.3-0.8 mg / ml, and the mass concentration of PVA is 1%-3%.

[0031] Optionally, in step (3), the spin coating includes pre-spinning and main spin;

[0032] And / or, the pre-spinning speed is 500-700 rpm, and / or, the pre-spinning time is 5-15 s;

[0033] And / or, the rotation speed of the main spin is 1800-2200 rpm, and / or, the duration of the main spin is 20-40 s.

[0034] Optionally, in step (4), the drying temperature is 35-40°C, and / or the drying time is 2-4 hours;

[0035] And / or, in step (4), the drying temperature is 37°C, and / or, the drying time is 3 hours;

[0036] And / or, the curing includes: ultraviolet light irradiation.

[0037] The application of the STM2457-PLGA nanomedicine and the artificial lens in the preparation of drugs for treating secondary cataracts.

[0038] The beneficial effects of the technical solutions provided in the embodiments of the present invention include at least the following:

[0039] 1. This invention provides a drug-loaded intraocular lens (IOL) with a drug-loaded coating precisely constructed on the non-optical region of the IOL (including the optical region edge and IOL haptics) using spin-coating technology. The coating has a uniform ring structure, and its thickness can be precisely controlled through process parameters, without significantly affecting the refractive properties of the IOL's optical component. The coating bonds tightly to the hydrophobic acrylate substrate, exhibits excellent mechanical stability, and can withstand the curling and compression of the IOL implant, making it less prone to detachment while fully preserving the IOL's foldability and structural stability. Furthermore, the manufacturing process is controllable, resulting in good quality uniformity.

[0040] 2. The drug-loaded coating of the present invention uses STM2457-PLGA nanomedicine as the core functional component, combined with a PVA matrix (PEG can be added to optimize performance). STM2457, as a highly efficient and selective METTL3 inhibitor, can regulate the m6A methylation level and target and inhibit the proliferation, migration and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs), thereby blocking the occurrence of posterior capsule opacification from the source of the pathogenic mechanism. The target is more precise and the anti-opause effect is more significant.

[0041] 3. The materials prepared in this invention all possess excellent biocompatibility: PLGA is a commonly used biodegradable material in clinical practice, and PVA and PEG (molecular weight 2000) have good hydrophilicity and biocompatibility, with no obvious toxicity or immunogenicity. After implantation into the eye, the coating has no significant toxic side effects on the cornea, iris, retina, and other tissues around the lens capsule, does not interfere with the angle of the anterior chamber and trabecular meshwork, and does not affect the circulation of aqueous humor within the eye. The biocompatibility fully meets the requirements for intraocular implants.

[0042] 4. The surface-modified intraocular lens of this invention can be sterilized with ethylene oxide, strictly meeting the sterility standards for intraocular implants. Its integrated STM2457 achieves long-term release through the controlled release effect of PLGA nanospheres. The optimized release period covers the high-incidence period of post-cataract surgery complications, far exceeding traditional short-term release systems. This continuously meets the long-term prevention and treatment needs after surgery, effectively reducing the risk of complications such as secondary cataracts.

[0043] 5. The drug-loaded sustained-release intraocular lens provided by this invention has broad-spectrum therapeutic potential: it can not only precisely prevent posterior capsule opacification by loading STM2457, but also target and regulate fibrosis by leveraging the regulatory effect of STM2457 on the m6A methylation pathway, significantly improving postoperative visual quality, surgical safety and clinical satisfaction of patients.

[0044] 6. The raw materials used in the preparation of the drug-loaded sustained-release coating of this invention (STM2457, PLGA, PVA, PEG, etc.) are all commonly used materials in clinical or industrial settings, with wide availability and economic feasibility. The coating is prepared using a microfluidic combined with spin coating process, which is simple and efficient. The resulting coating has a regular surface morphology, high drug loading and controllable release, excellent biocompatibility, and strong repeatability and stability of the preparation process, facilitating standardized production.

[0045] 7. The core instruments used in this invention, such as microfluidic chips and spin coaters, are all mature industrial equipment, readily available, and have low promotion costs. The solvents used in the preparation process (acetonitrile, dichloromethane, etc.) can be processed using conventional methods, resulting in low polluting raw materials and minimal environmental impact during large-scale production. The overall process is highly operable, economically cost-controllable, requires no complex or specialized equipment, and has a solid foundation for large-scale industrial production. Attached Figure Description

[0046] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0047] Figure 1 This is a result diagram provided in Experimental Example 1 of the present invention, wherein... Figure 1 Figure A shows the Tyndall effect observed under red laser light on PLGA, STM2457 solutions and synthesized PLGA and STM2457-PLGA nanospheres. In the figure, sol represents the solution and NPs represents the nanospheres. Figure 1 Image B is a transmission electron microscope image showing the morphology of PLGA and STM2457-PLGA nanospheres, scale bar=500 nm. Figure 1 C in the figure is a graph of the size of nanoparticles detected by dynamic light scattering, n=3;

[0048] Figure 2 This is a result diagram provided in Experimental Example 2 of the present invention; Figure 2 Figure A shows the results of X-ray photoelectron spectroscopy detection of characteristic elemental peak changes; Figure 2Figure B shows the results of Fourier transform infrared spectroscopy detection of changes in characteristic functional groups; Figure 2 C in the diagram shows the results of the water contact angle experiment, where n=3;

[0049] Figure 3 This is a result diagram provided in Experiment Example 3 of the present invention; Figure 3 Image A is a scanning electron microscope image showing the morphological features and thickness of the nanosphere coating, with a scale bar of 10 μm / 1 μm. Figure 3 Figure B shows the results of the biological hemolysis test, where 1: Negative control, 2: Positive control, 3: PLGA NPs, 4: STM2457-PLGA NPs, 5: PLGA@IOL, and 6: STM2457-PLGA@IOL. Figure 3 C in the figure is a quantitative statistical graph of the biological hemolysis test, n=3;

[0050] Figure 4 This is a result diagram provided in Experiment Example 4 of the present invention; Figure 4 Image A shows the anterior segment slit-lamp images taken at 1, 2, 3, and 4 weeks post-phacoemulsification and implantation of a modified intraocular lens in rabbit eyes. Figure 4 B is a quantitative statistical turbidity rating analysis chart for A; Figure 4 In the middle C is the Miyake-apple diagram and the corresponding HE staining diagram. The black arrows represent fibroblast clusters proliferating in the posterior capsule. Scale bar = 100 μm. Figure 4 The image in D is a HE staining image of the cornea, optic nerve, retina, iris, and ciliary body after IOL implantation, with a scale bar of 100 μm. Detailed Implementation

[0051] The technical solution of the present invention will now be described with reference to the accompanying drawings.

[0052] In embodiments of the present invention, words such as "exemplarily," "for example," etc., are used to indicate that something is an example, illustration, or description. Any embodiment or design described as "exemplary" in the present invention should not be construed as being more preferred or advantageous than other embodiments or designs. Specifically, the use of the word "exemplary" is intended to present the concept in a concrete manner. Furthermore, in embodiments of the present invention, the meaning expressed by "and / or" can be both, or either one.

[0053] In this invention, PLGA refers to polylactic acid-glycolic acid copolymer, which is a biodegradable functional polymeric organic compound formed by the random polymerization of lactic acid and glycolic acid, with CAS number 34346-01-5.

[0054] In this invention, PVA refers to polyvinyl alcohol, which is a white, flaky, flocculent, or powdery solid that is odorless and soluble in water.

[0055] In this invention, STM2457 is a highly efficient and selective small molecule drug for m6A methylation modification, an orally active METTL3 inhibitor that regulates m6A levels in a METTL3 enzyme activity-dependent manner, affecting the translation of m6A-positive genes, and significantly inhibiting the progression of acute myeloid leukemia. In recent years, STM2457 has also been found to inhibit cardiopulmonary fibrosis, renal fibrosis, and liver fibrosis, but its application in the anti-fibrotic treatment of polycythemia vera (PCO) has not yet been reported. Specific information about STM2457 is as follows:

[0056] Molecular weight 444.53;

[0057] Molecular formula C 25 H 28 N6O2;

[0058] CAS No. 2499663-01-1;

[0059] Molecular formula:

[0060] .

[0061] This invention belongs to the field of drug-encapsulated intraocular lenses (IOLs) and discloses a method for preparing modified IOLs based on surface-encapsulated small molecule drug m6A methylation METTL3 inhibitor STM2457.

[0062] Based on the research of our research group, STM2457 can significantly inhibit the EMT process, providing a novel target for targeted therapy of secondary cataracts. During the development of EMT, m6A methylation is activated. Our experiments have demonstrated that inhibiting the assembly of the METTL3-METTL14-WTAP complex during m6A methylation can suppress EMT.

[0063] Therefore, based on this, the inventors constructed a surface modification system with excellent biocompatibility and good mechanical stability, achieving efficient encapsulation and targeted long-term sustained release of STM2457 on the surface of the intraocular lens, significantly improving its application effect in the treatment of secondary cataracts and providing a novel solution for the prevention and treatment of clinical PCO. Modified intraocular lenses based on surface-encapsulated functional small molecule drugs can achieve targeted and long-term sustained release of drugs within the eye, significantly improving the inhibitory effect of drugs on residual LECs while reducing systemic toxicity, thereby reducing the incidence of secondary cataracts.

[0064] This invention utilizes microfluidic technology to prepare STM2457-PLGA nanospheres and combines this with spin-coating to construct modified intraocular lenses (IOLs). The microfluidically synthesized nanomedicines achieve efficient loading and controlled sustained release of STM2457, while the spin-coating method produces uniformly coated IOLs with minimal impact on their physical properties. The main objective of this invention is to provide a process-controllable and performance-stable method for preparing STM2457 nanomedicines and modified IOLs.

[0065] In a preferred embodiment of the present invention, a surface-modified intraocular lens is disclosed, wherein the non-optical region of the intraocular lens has a drug-loaded sustained-release coating, the drug-loaded sustained-release coating being composed of STM2457-PLGA nanomedicine and a PVA matrix, wherein STM2457 is an m6A methylation METTL3 inhibitor and PLGA is a drug carrier material, and the drug-loaded coating can achieve targeted treatment of posterior cataracts.

[0066] Preferably, the non-optical region includes the edge of the optical region of the plate-shaped intraocular lens and the haptic of the intraocular lens; the STM2457-PLGA nanomedicine has a particle size of 50-300 nm, the drug-loaded sustained-release coating has a ring structure, and the coating thickness can be precisely controlled by the preparation process. In one embodiment, the average particle size of the STM2457-PLGA nanomedicine of the present invention is 230.15±8.14 nm.

[0067] The application of the drug-loaded sustained-release intraocular lens or the drug-loaded sustained-release intraocular lens prepared by the preparation method is to load the ophthalmic drug STM2457 related to m6A methylation regulation. After the intraocular lens is implanted into the eye, it can continuously release STM2457 through the drug-loaded coating for targeted treatment of secondary cataracts.

[0068] To make the technical problems, technical solutions and advantages of the present invention clearer, a detailed description will be given below in conjunction with the accompanying drawings and specific embodiments.

[0069] Unless otherwise specified, the experimental methods described in the following embodiments are conventional experimental methods well known to those skilled in the art, and are performed according to the techniques or conditions described in the literature in this field or according to the product instructions. Where specific conditions are not specified in the experimental methods, they are generally operated under conventional conditions.

[0070] Unless otherwise specified, all materials and reagents described in the following examples are commercially available. PLGA can be purchased from, for example, Sigma (Mw: 40,000-75,000). PVA can be purchased from, for example, Thermo Fisher Scientific (product number: 041243).

[0071] Example 1

[0072] The preparation method of STM2457-PLGA microfluidic nanomedicine is as follows:

[0073] Step S1: Preparation of oil phase system: Dissolve STM2457 (concentration 1 mg / ml) and PLGA (concentration 5 mg / ml) in acetonitrile and stir magnetically for 30 min until completely dissolved to form a homogeneous oil phase solution.

[0074] Step S2: Prepare an aqueous system: Prepare a 2% PVA aqueous solution and stir until transparent to serve as a dispersion medium.

[0075] Step S3: Microfluidic synthesis of nanospheres: Adjust the flow rate and inject the oil phase and water phase into the microfluidic chip at a volume ratio of 2:6. Under 25°C, an oil-in-water emulsion is formed. Collect the effluent, and the Tyndall effect can be seen in the collected liquid using a red laser pointer.

[0076] Step S4, solidification and purification: The collected emulsion was stirred at room temperature for 4 hours to allow solvent evaporation and solidification, then centrifuged (9000 rpm, 10 min), washed 3 times with deionized water, and freeze-dried (-50℃, 12 h) to obtain STM2457-PLGA nanomedicine.

[0077] The preparation method of STM2457 modified intraocular lens is as follows:

[0078] Step S5, IOL pretreatment: Select hydrophobic acrylate IOL, and ultrasonically clean it with anhydrous ethanol and deionized water for 15 min in sequence. After drying with nitrogen, sterilize it with ultraviolet light (254nm, 30 min) for later use.

[0079] Step S6: Preparation of spin-coating solution: The nanomedicine prepared in step S4 is dispersed in a PVA aqueous solution and ultrasonically dispersed for 20 min to form a uniform spin-coating solution with a concentration of 0.5 mg / ml. The effluent synthesized by microfluidics can also be used directly for coating, or the concentration of the effluent can be adjusted by using PVA to prevent the spin-coating solution from being too viscous and affecting implantation.

[0080] Step S7: Spin-coating to prepare a ring-shaped coating: Fix IOL on the stage of the spin coater, add 10 μl of spin coating liquid, set the parameters: 600 rpm for pre-spinning for 10 s, 2000 rpm for main spinning for 30 s, and use centrifugal force to form a ring-shaped coating, and let it air dry naturally.

[0081] Step S8, Curing and Post-treatment: The modified IOL was dried in a constant temperature oven at 37℃ for 2 hours, and then cross-linked with ultraviolet light (254nm, 15min) to enhance the stability of the coating. After rinsing with sterile PBS, it was sterilized with ethylene oxide to obtain the STM2457 modified intraocular lens.

[0082] Example 2

[0083] The preparation method is basically the same as in Example 1, except that...

[0084] 1. In step S1, acetonitrile can be replaced with dichloromethane, and the stirring temperature should be controlled at 20-25℃ to avoid drug degradation.

[0085] 2. The PVA concentration in step S2 can be adjusted within the range of 1%-3% to suit different coating thickness requirements.

[0086] 3. In step S3, the microfluidic chip channel width is 100μm and the temperature control accuracy is ±0.5℃ to ensure that the nanosphere particle size is uniform (50-300nm).

[0087] 4. In step S4, the centrifugation speed can be adjusted to 8000-10000 rpm, and the number of washing cycles can be increased to 4 to improve purity.

[0088] 5. The concentration of the spin coating solution in step S6 can be optimized within the range of 0.3-0.8 mg / ml to balance the drug loading and coating flexibility.

[0089] 6. The spin coating parameters in step S7 can be adjusted in stages: pre-rotation speed 500-700 rpm, main rotation speed 1800-2200 rpm, to precisely control the thickness gradient of the annular coating.

[0090] 7. In step S8, the drying temperature can be adjusted to 35-40℃ and the drying time extended to 3 hours to enhance the adhesion between the coating and the IOL substrate.

[0091] 8. 0.5% PEG (molecular weight 2000) can be added to the spin coating solution to improve the hydrophilicity and biocompatibility of the coating.

[0092] Example 3

[0093] The preparation method of STM2457-PLGA nanomedicine is the same as that in Example 1.

[0094] The method for preparing the drug-loaded sustained-release intraocular lens includes the following steps:

[0095] Step 1: Pretreatment of intraocular lens: Select hydrophobic acrylate intraocular lens, ultrasonically clean it with anhydrous ethanol and deionized water for 15 minutes in sequence, dry it with nitrogen, and then disinfect it with 254nm ultraviolet light for 30 minutes for later use.

[0096] Step 2: Preparation of spin coating solution: Disperse STM2457-PLGA nanomedicine in PVA aqueous solution and ultrasonically disperse for 20 min to form a uniform spin coating solution. 0.5% PEG (molecular weight 2000) can be added to the spin coating solution to improve the hydrophilicity and biocompatibility of the coating.

[0097] Step 3: Spin-coating to prepare a ring-shaped coating: Fix the pretreated intraocular lens on the stage of the spin coater, add 10 μl of spin coating liquid, set the pre-spin and main spin parameters, and use centrifugal force to form a ring-shaped drug-loaded sustained-release coating in the non-optical area, and let it air dry naturally;

[0098] Step 4, Curing and Post-treatment: Place the intraocular lens with the ring coating in a constant temperature oven at 35-40℃ for 2-3 hours to dry, cross-link it with 254nm ultraviolet light for 15 minutes to enhance the stability of the coating, and rinse with sterile PBS to remove unbound drugs and impurities.

[0099] Step 5: Disinfect the intraocular lens and then seal it in a package.

[0100] The concentration of STM2457-PLGA nanomedicine in the spin-coating solution is 0.3-0.8 mg / ml, and the mass concentration of PVA is 1%-3%; the initial concentration of PLGA in the preparation of the nanomedicine is 5 mg / ml, and the initial concentration of STM2457 is 1 mg / ml.

[0101] In step three, the pre-rotation speed is 500-700 rpm and the pre-rotation time is 10s; the main rotation speed is 1800-2200 rpm and the main rotation time is 30s. The thickness gradient of the annular coating is precisely controlled by adjusting the rotation speed in stages.

[0102] In step four, the intensity of ultraviolet crosslinking light can be adjusted according to the coating thickness to ensure uniform crosslinking; the drying temperature is preferably 37°C and the drying time is preferably 3 hours to enhance the adhesion between the coating and the intraocular lens substrate.

[0103] In step five, ethylene oxide is used for sterilization, and the sterilization process meets the sterility standards for ophthalmic medical devices.

[0104] Experimental Example 1

[0105] The Tyndall effect was observed under red laser light when PLGA, STM2457 solutions, and PLGA and STM2457-PLGA nanospheres synthesized in Example 1 were exposed to the solutions. The microspheres reflected red light, thus forming a Tyndall beam, while the solutions, due to their small particle size, could not form a reflected beam.

[0106] The morphology of PLGA and STM2457-PLGA nanospheres was observed using transmission electron microscopy. The nanoparticle size was determined using dynamic light scattering and measured three times at 25°C using a Malvern particle size analyzer.

[0107] Experimental results:

[0108] See the experimental results. Figure 1 . Figure 1Figure A shows the Tyndall effect observed under red laser light on PLGA, STM2457 solutions and synthesized PLGA and STM2457-PLGA nanospheres. In the figure, sol represents the solution and NPs represents the nanospheres. Figure 1 Image B is a transmission electron microscope image showing the morphology of PLGA and STM2457-PLGA nanospheres, scale bar=500 nm. Figure 1 C in the figure is a graph of the size of nanoparticles detected by dynamic light scattering, n=3.

[0109] exist Figure 1 In this context, PLGA sol; STM2457 sol, PLGA NPs, and STM2457-PLGA NPs refer to PLGA solution, STM2457 solution, PLGA nanospheres, and STM2457-PLGA nanospheres, respectively. Ctrl@IOL is a blank crystal; PLGA@IOL is IOL coated with PLGA nanospheres; STM2457-PLGA@IOL is IOL coated with STM2457-PLGA nanospheres. Figures 2 to 4 The meaning of the corresponding logo is also related to Figure 1 same).

[0110] from Figure 1 As shown in Figure A, the synthesis of PLGA-encapsulated m6A methyltransferase-related METTL3 inhibitor STM2457 nanospheres using microfluidic technology revealed that, compared to solutions of PLGA and the small molecule drug STM2457, the nanospheres synthesized using acetonitrile as a solvent exhibited a significant Tyndall effect. These results demonstrate the successful synthesis of PLGA-encapsulated STM2457 nanospheres.

[0111] from Figure 1 As shown in Figures B and C, the nanoparticle size was characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). The results indicate that the nanoparticle size of PLGA after successfully encapsulating STM2457 was significantly increased compared to the PLGA group, reaching 230.15 ± 8.41 nm. These results demonstrate that the encapsulation of STM2457 in PLGA was successful.

[0112] Experimental Example 2

[0113] Two sets of synthesized nanospheres (STM2457-PLGA and PLGA nanospheres) were coated onto the surface of the artificial crystal using a spin-coating method. X-ray photoelectron spectroscopy (XPS) was used to detect changes in characteristic elemental peaks. Fourier transform infrared spectroscopy was used to detect changes in characteristic functional groups.

[0114] The water contact angle was determined using a water contact angle experiment. The specific experimental steps are as follows: An equal volume of water droplets was placed on the crystal surface, and then a high-speed camera was used to capture images of the droplets. The machine then analyzed the angle of the water droplets.

[0115] Experimental results:

[0116] See the experimental results. Figure 2 .

[0117] Figure 2 Figure A shows the results of X-ray photoelectron spectroscopy detection of characteristic elemental peak changes. From... Figure 2 As shown in Figure A, the data indicates that when the PLGA successfully encapsulates the STM2457, transitions to Na1s, N1s, O1s, and C1s peaks occur compared to the control group. These results demonstrate that the encapsulation was successful compared to the control group, as high-element peaks were observed.

[0118] Figure 2 Image B is the result of Fourier transform infrared spectroscopy detecting changes in characteristic functional groups. From... Figure 2 As shown in Figure B, Fourier Transform Infrared Spectrometer (FTIR) detection revealed changes in the characteristic hydrophilic peaks and -OH functional groups of PLGA in both the PLGA-coated STM2457 and the control group. These results indicate that the coating was successful compared to the control group, as functional group transitions were observed.

[0119] Figure 2 Figure C shows the results of the water contact angle experiment, where n=3. From... Figure 2 As shown in Figure C, the water contact angle test results indicate that the water contact angle of the experimental group is smaller, and the hydrophobicity of the modified IOL is slightly reduced. These results suggest that the modification slightly reduces the hydrophobicity of the IOL but has little impact on its function.

[0120] Experimental Example 3

[0121] Scanning electron microscopy was used to observe the spherical morphology of the nanospheres and the thickness of the nanosphere coating.

[0122] The specific steps and quantitative statistical steps of the biological hemolysis test are as follows: Use a blood collection tube to extract an appropriate amount of rabbit ear vein blood. Wash the red blood cells with PBS before each use at room temperature and 3000 rpm for 2-3 times until there is no obvious red (slightly yellow) in the supernatant. Take 200ul of the substrate from the centrifuge tube and dilute it to 10ml for use, thus preparing a 2% red blood cell suspension.

[0123] Mix 0.5 ml of each material group (groups 1-6 in the figure) with 0.5 ml of 2% red blood cell solution. After incubation at room temperature, 100 µl of each group was transferred to a 96-well plate, and absorbance was measured at a wavelength of 570 nm. Water and PBS were used as positive and negative controls, respectively. Each sample had three parallel controls. Hemolysis rate (%) = (sample absorption - negative control absorption) / (positive control absorption - negative control absorption) x 100%. A hemolysis rate exceeding 5% was considered hemolysis.

[0124] Experimental results:

[0125] See the experimental results. Figure 3 . Figure 3 Image A is a scanning electron microscope image showing the morphological features and thickness of the nanosphere coating, with a scale bar of 10 μm. Figure 3 Figure B shows the results of the biological hemolysis test, where 1: Negative control, 2: Positive control, 3: PLGA NPs, 4: STM2457-PLGA NPs, 5: PLGA@IOL, and 6: STM2457-PLGA@IOL. Figure 3 C is a quantitative statistical graph of the biological hemolysis test, n=3.

[0126] from Figure 3 As shown in Figure A, scanning electron microscopy (SEM) revealed that the coating thickness of the modified IOL in both groups (experimental group: PLGA-encapsulated STM2457 NPs@IOL; control group: PLGA NPs@IOL) was approximately 5-6 μm, and the coating thickness was relatively uniform. These results indicate that the coating thickness of the modified IOL is relatively uniform.

[0127] from Figure 3 As shown in Figures B and C, the hemolysis experiment revealed that the hemolysis rate of the nanospheres was approximately 15%, indicating biotoxicity. However, after IOL modification, the hemolysis rate decreased to 2.5%, demonstrating the biosafety of modified IOL. These results indicate that modified IOL is biosafe.

[0128] Test Example 4

[0129] After phacoemulsification and aspiration of rabbit eyes, the modified intraocular lens of Example 1 was implanted. Anterior segment photography was performed using a slit lamp at 1, 2, 3, and 4 weeks postoperatively, and quantitative statistical turbidity rating analysis was conducted.

[0130] Miyake-apple images and corresponding tissue H&E staining images were taken. H&E staining was also performed on the cornea, optic nerve, retina, iris, and ciliary body after IOL implantation.

[0131] Experimental results:

[0132] See the experimental results. Figure 4 . Figure 4 Image A shows the anterior segment slit-lamp images taken at 1, 2, 3, and 4 weeks post-phacoemulsification and implantation of a modified intraocular lens in rabbit eyes. Figure 4 B is a quantitative statistical turbidity rating analysis chart for A; Figure 4 In the middle C is the Miyake-apple diagram and the corresponding HE staining diagram. The black arrows represent fibroblast clusters proliferating in the posterior capsule. Scale bar = 100 μm. Figure 4 The image in D is a HE staining image of the cornea, optic nerve, retina, iris, and ciliary body after IOL implantation, with a scale bar of 100 μm.

[0133] from Figure 4 As shown in Figures A and B, the IOL group with STM2457 encapsulated in PLGA significantly inhibited PCO. Quantitative statistical turbidity rating analysis showed that the experimental group mainly had mild to moderate turbidity, which was significantly reduced compared to the PLGA@IOL and Ctrl@IOL groups. These results indicate that the IOL group with STM2457 encapsulated in PLGA significantly inhibited PCO.

[0134] from Figure 4 As shown in the middle C diagram, the Miyake-apple plot and H&E staining results indicate that the experimental group showed few fibroblast clusters and low crystal proliferation in the posterior capsule at the equator. These results suggest that the PLGA-encapsulated STM2457-containing IOL group significantly inhibited PCO.

[0135] from Figure 4 As can be seen from the results, after implantation, rabbit eyeballs were harvested, embedded, and then stained with H&E. No significant changes in the structure of the cornea, optic nerve, retina, iris, and ciliary body were observed, indicating that the modified intraocular lens has good implantation safety.

[0136] The above experimental examples demonstrate that the surface modification system has good mechanical stability, achieving efficient encapsulation and targeted long-term sustained release of STM2457 on the surface of the intraocular lens, significantly improving its application effect in the treatment of secondary cataracts. While reducing systemic toxic side effects, it significantly enhances the inhibitory effect of the drug on residual LECs, thereby reducing the incidence of secondary cataracts.

[0137] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. An STM2457-PLGA nanomedicine, characterized in that, The preparation method of the STM2457-PLGA nanomedicine includes: preparing nanospheres by injecting an oil phase including STM2457 and PLGA and an aqueous phase including PVA into a microfluidic chip, and obtaining the STM2457-PLGA nanomedicine by freeze-drying the nanospheres, wherein the particle size of the STM2457-PLGA nanomedicine is 50-300 nm.

2. The method for preparing STM2457-PLGA nanomedicine according to claim 1, characterized in that, The preparation method includes: (1) Preparation of oil phase solution: STM2457 and PLGA are dissolved in an organic solvent; (2) Preparation of aqueous solution: Prepare PVA aqueous solution; (3) Microfluidic synthesis of nanospheres: The oil phase solution and the aqueous phase solution are injected into a microfluidic chip to form an oil-in-water emulsion, and the effluent is collected; (4) Curing: The effluent from step (3) is cured by solvent evaporation and freeze-dried to obtain the STM2457-PLGA nanomedicine.

3. The preparation method according to claim 2, characterized in that, In step (1), the concentration of STM2457 is 0.5-1.5 mg / ml, and / or the concentration of PLGA is 4-6 mg / ml; And / or, in step (1), the concentration of the STM2457 is 1 mg / ml, and / or, the concentration of the PLGA is 5 mg / ml; And / or, in step (2), the mass concentration of the PVA aqueous solution is 1-3%; And / or, in step (2), the mass concentration of the PVA aqueous solution is 2%; And / or, in step (3), the volume ratio of the oil phase solution to the aqueous phase solution is (1-3):(5-7); And / or, in step (3), the volume ratio of the oil phase solution to the aqueous phase solution is 2:6; And / or, in step (4), the freeze-drying conditions are: -40 to -60°C, 9-15 h; And / or, in step (4), the freeze-drying conditions are: -50°C, 12h.

4. An intraocular lens for treating secondary cataracts, characterized in that, The non-optical region of the intraocular lens is coated with a drug-loaded sustained-release coating, the drug-loaded sustained-release coating comprising: the STM2457-PLGA nanomedicine according to claim 1.

5. The intraocular lens according to claim 4, characterized in that, The non-optical region includes the edge of the optical region of the plate-shaped intraocular lens and / or the haptic of the intraocular lens; And / or, the drug-loaded sustained-release coating has a ring structure.

6. The method for preparing an intraocular lens according to any one of claims 4-5, characterized in that, Includes the following steps: (1) Pretreatment of intraocular lens: Disinfect the intraocular lens; (2) Preparation of spin coating solution: The STM2457-PLGA nanomedicine according to claim 1 is dispersed in PVA aqueous solution to obtain spin coating solution; (3) Preparation of ring coating: The spin coating liquid from step (2) is added to the non-optical area of ​​the intraocular lens from step (1) and spin coated to form the drug-loaded sustained-release coating; (4) Curing: The artificial lens obtained in step (3) is dried and cured to obtain the artificial lens.

7. The preparation method according to claim 6, characterized in that, In step (1), the intraocular lens is a hydrophobic acrylate intraocular lens; And / or, in step (2), the spin coating solution further includes: 0.5% PEG, wherein the molecular weight of the PEG is 2000; And / or, in step (2), the concentration of STM2457-PLGA nanomedicine in the spin coating solution is 0.3-0.8 mg / ml, and the mass concentration of PVA is 1%-3%.

8. The preparation method according to claim 6, characterized in that, In step (3), the spin coating includes pre-spinning and main spin; And / or, the pre-spinning speed is 500-700 rpm, and / or, the pre-spinning time is 5-15 s; And / or, the rotation speed of the main spin is 1800-2200 rpm, and / or, the duration of the main spin is 20-40 s.

9. The preparation method according to claim 6, characterized in that, In step (4), the drying temperature is 35-40°C, and / or the drying time is 2-4 hours; And / or, in step (4), the drying temperature is 37°C, and / or, the drying time is 3 hours; And / or, the curing includes: ultraviolet light irradiation.

10. The use of the STM2457-PLGA nanomedicine according to claim 1 and the intraocular lens according to any one of claims 4-5 in the preparation of a drug for treating secondary cataracts.

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