A hydrophilic sustained-release coating intraocular lens loaded with carbon quantum dots nanoscale enzyme, and a preparation method and application thereof

Abstract

The application discloses a hydrophilic sustained-release coating intraocular lens loaded with carbon quantum dot nanoscale enzyme and a preparation method and application thereof, and relates to the field of medical materials.The application adopts a spin coating process which is easy to scale up production, and combines a low-temperature curing mode to realize simple and efficient preparation of a functional coating.Relying on good film-forming performance of a biomedical polymer material and interface interaction between the biomedical polymer material and the carbon quantum dot nanoscale enzyme, a uniform and stable functional coating can be formed on the surface of the intraocular lens, so that the stability, repeatability and industrial application potential of the coating are improved.Through regulation of the molecular structure, hydrophilicity or hydrophobicity and surface charge characteristics of the biomedical polymer material, the interface bonding strength between the biomedical polymer material and the carbon quantum dot nanoscale enzyme can be effectively adjusted, so that the release rate and release period of the carbon quantum dot nanoscale enzyme can be controllably adjusted, and the stability, safety and long-acting effect of the carbon quantum dot nanoscale enzyme in the sustained release process are further improved.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to a hydrophilic sustained-release coated intraocular lens loaded with carbon quantum dot nanozymes, its preparation method, and its application. Background Technology

[0002] Cataracts are one of the most common causes of blindness worldwide, with over 90 million new cases annually. Currently, phacoemulsification to remove the diseased lens and implant an intraocular lens (IOL) is the most effective treatment for cataracts. However, numerous clinical studies have shown that posterior capsular opacification (PCO), also known as posterior capsular opacification, is the most common long-term complication after phacoemulsification and IOL implantation, leading to decreased visual acuity and impaired visual quality post-surgery. The incidence of PCO in adult patients is approximately 20%–40% within 2–5 years post-surgery, while it can reach almost 100% in infants and young children. Research indicates that PCO is primarily related to the continued proliferation, migration, and epithelial-mesenchymal transition of residual lens epithelial cells, ultimately leading to posterior capsular fibrosis and opacity. Despite the use of improved surgical techniques and novel IOL designs, it remains difficult to fundamentally suppress the occurrence of PCO. Currently, Nd:YAG laser posterior capsulotomy is the main clinical treatment for peripheral lens opacity (PCO). However, this method may cause complications such as retinal detachment, macular cystoid edema, and increased intraocular pressure, and it cannot effectively prevent the abnormal proliferation and migration of residual lens epithelial cells. Therefore, functional modification of the intraocular lens surface to achieve continuous regulation of the behavior of residual lens epithelial cells, thereby safely and effectively inhibiting the occurrence of PCO, has significant clinical application value.

[0003] In the prior art, relevant patents have been reported, such as Chinese patent CN110215519A "Drug-modified intraocular lens and its preparation method and application" and Chinese patent CN118340942A "An intraocular lens modified with a superhydrophilic coating for controllable sustained-release drugs and its preparation method". Although the PCO incidence has been reduced to a certain extent, the following shortcomings still exist: (1) Existing drug-loaded intraocular lenses mostly adopt physical embedding or adsorption of drugs. The stability of the drug-coating combination is limited, and the release rate is prone to uncontrollable problems and insufficient effective action time, making it difficult to achieve (1) Long-term continuous regulation of residual cells after cataract surgery, while rapid drug release in a short period of time may increase the risk of intraocular irritation and toxic side effects; (2) Existing functional coatings are prone to adsorbing biological pollutants such as cell debris, proteins and inflammatory secretions on the surface. Long-term deposition may affect the stability of the coating interface and the drug diffusion efficiency, thereby reducing the continuous treatment effect; (3) Some functional coatings of artificial lenses have problems such as complex preparation process, poor repeatability and insufficient adhesion stability. Moreover, the drug loading, coating thickness and release behavior are difficult to control precisely, which is not conducive to product quality control and subsequent industrial application.

[0004] Therefore, how to construct a uniform and stable nanozyme functionalized coating on the surface of an intraocular lens and achieve the continuous and controllable release of carbon quantum dot nanozymes and the synergistic regulation of interfacial antifouling properties, thereby inhibiting the occurrence of postoperative polio in the long term, has become a key technical problem that urgently needs to be solved in this field. Summary of the Invention

[0005] To address the technical deficiencies of existing technologies, this invention provides a hydrophilic sustained-release coated intraocular lens (IOL) loaded with carbon quantum dot nanozymes, its preparation method, and its application, thereby solving the problem of high post-implantation polio (PCO) rates in existing IOLs. The preparation method is simple to operate, has good repeatability, and produces a highly uniform and stable coating, demonstrating excellent potential for large-scale preparation and application.

[0006] The technical solution adopted in this invention is: a hydrophilic sustained-release coating intraocular lens loaded with carbon quantum dot nanozymes, wherein a stable carbon quantum dot nanozyme sustained-release functional coating is formed on the surface of the intraocular lens, and the carbon quantum dot nanozyme sustained-release functional coating is formed by curing a functional coating liquid composed of biodegradable polymer materials and carbon quantum dot nanozymes.

[0007] The carbon quantum dot nanozyme is prepared by hydrothermal reaction, with baicalin as the carbon source and any one or two amino acids as the nitrogen source.

[0008] The concentration of carbon quantum dot nanozymes in the functionalized coating solution is 0.5-100 mg / mL.

[0009] The content of biodegradable polymer materials in the functionalized coating liquid is 3-20 wt%.

[0010] The molar ratio of amino acids to baicalin in the carbon quantum dot nanozyme is 0.1:5.0-5.0:0.1.

[0011] The biodegradable polymer material is one or more of polylactic acid-glycolic acid copolymer (PLGA), polyvinylpyrrolidone (PVP), polyacrylamide (PAM), polyethylene glycol (PEG), and polyvinyl alcohol (PVA).

[0012] The carbon quantum dot nanozyme is prepared by the following steps: A carbon source and a nitrogen source were added to a three-necked flask, along with 5-35 mL of a mixed solution of ethanol and deionized water. The mixture was stirred to form a homogeneous solution. The resulting mixed solution was then transferred to a hydrothermal reactor for hydrothermal reaction at a temperature of 100-230ºC for 2-24 h. After dialysis purification, carbon quantum dot nanozymes were obtained. The carbon source was baicalin, and the nitrogen source was any one or two amino acids.

[0013] The volume ratio of ethanol to deionized water is 10:1 to 1:10.

[0014] A method for preparing a hydrophilic sustained-release coated intraocular lens loaded with carbon quantum dot nanozymes includes the following steps: (1) Plasma activation treatment of the intraocular lens substrate; (2) Carbon quantum dot nanozymes and biodegradable polymer materials are formulated into a coating liquid, and the coating liquid is applied to the surface of the artificial lens substrate after plasma activation by spin coating. (3) Curing at 20~50℃ for 0.5-24 h forms a stable carbon quantum dot nanoenzyme sustained-release functional coating on the surface of the artificial lens.

[0015] The plasma activation treatment involves treating the surface of the intraocular lens using a plasma instrument. The oxygen flow rate for the plasma activation treatment is 5-20 cm³ / min, the treatment power is 50-100 W, and the treatment time is 1-6 min.

[0016] Application of a hydrophilic sustained-release coated intraocular lens loaded with carbon quantum dot nanozymes in the preparation of anti-PCO biomaterials.

[0017] The beneficial effects of this invention are as follows: This invention provides an intraocular lens with a hydrophilic sustained-release coating loaded with carbon quantum dot nanozymes, its preparation method, and its application. This invention employs a spin-coating process that is easy to scale up for production, combined with a low-temperature curing method, to achieve simple and efficient preparation of the functional coating. Relying on the excellent film-forming properties of biomedical polymer materials and their interfacial interaction with carbon quantum dot nanozymes, a uniform and stable functionalized coating can be formed on the surface of the intraocular lens, thereby improving the stability, repeatability, and industrial application potential of the coating. By controlling the molecular structure, hydrophilicity / hydrophobicity, and surface charge characteristics of the biomedical polymer materials, the interfacial binding strength between them and the carbon quantum dot nanozymes can be effectively adjusted, thereby achieving controllable regulation of the release rate and release cycle of the carbon quantum dot nanozymes, further improving the stability, safety, and long-lasting effect of the nanozymes during continuous release. Attached Figure Description

[0018] Figure 1 The structural characterization results of carbon quantum dot nanozymes include morphological and compositional analysis.

[0019] Figure 2 The results show the enzyme-like catalytic activity of carbon quantum dot nanozymes.

[0020] Figure 3 Cumulative release behavior curves of carbon quantum dot nanozymes in intraocular lenses modified with different functional coatings. Detailed Implementation

[0021] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] Example 1 Preparation of carbon quantum dot nanozymes: Baicalin and arginine were added to a three-necked flask, along with 5-35 mL of a mixture of ethanol and deionized water, and stirred to form a homogeneous solution. The resulting solution was then transferred to a hydrothermal reactor for hydrothermal reaction at 100-230ºC for 2-24 h. After dialysis purification, carbon quantum dot nanozymes were obtained. Arginine can be replaced with any one or two amino acids.

[0023] The specific preparation steps of an intraocular lens with a carbon quantum dot nanoenzyme coating are as follows: (1) The surface of polyacrylate intraocular lenses was activated by a low-temperature plasma instrument. The treatment conditions were: oxygen flow rate 12 cm³ / min, treatment power 60 W, and treatment time 5 min. The lenses were then set aside for use after treatment.

[0024] (2) A functional inner coating solution containing different concentrations of carbon (50 μg / mL, 100 μg / mL) quantum dot nanozymes, polyvinylpyrrolidone (PVP), and polylactic-co-glycolic acid copolymer (PLGA) was prepared. By adjusting the molecular weight and lactic acid / glycolic acid ratio of PLGA, the molecular weight and content of PVP, and introducing functional modifications with different surface charge characteristics, the density, hydrophilicity / hydrophobicity, and interfacial charge distribution of the polymer matrix can be synergistically controlled. This alters the hydrogen bonding, electrostatic adsorption, and spatial diffusion resistance between the polymer matrix and the carbon quantum dot nanozymes, enabling controllable adjustment of the interfacial binding strength of the nanozymes in the inner coating, and further achieving precise control of their sustained-release behavior and duration.

[0025] (3) Spin-coating the functionalized coating liquid prepared in step (2) onto the surface of the artificial lens after low-temperature plasma treatment, and allowing it to stand and cure at room temperature for 6 h to form a stable carbon quantum dot nanozyme sustained-release functional coating on the surface of the artificial lens, thereby obtaining an artificial lens loaded with carbon quantum dot nanozyme.

[0026] Carbon quantum dot nanozyme sustained-release performance test: Artificial lenses coated with carbon quantum dot nanozymes were placed in 5 mL of PBS buffer (pH 7.4) and in vitro release experiments were conducted at a constant temperature of 37 ℃. At different time points (0.5, 1, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 80, and 90 days), 500 µL of the release solution was aspirated for detection, and an equal volume of fresh PBS buffer was simultaneously added to maintain a constant total volume of the release system.

[0027] The absorbance of the release solution was determined by ultraviolet-visible spectrophotometry, and the cumulative release amount of carbon quantum dot nanozymes was calculated using a pre-established standard curve. The results are as follows: Figure 3 As shown.

[0028] Hydrophilicity testing of the coating: The water contact angle of the intraocular lens (IOL) surface loaded with carbon quantum dot nanozyme coating was tested using a contact angle meter. Deionized water was used as the test liquid, with a droplet volume of 5 μL. The test results are shown in Table 1. Compared with the 87.8° water contact angle of the unmodified IOL surface, the water contact angles of the IOL surfaces loaded with carbon quantum dot nanozyme-biopolymer composite coatings of different concentrations were significantly reduced, indicating that the constructed functional coating has good hydrophilicity. PVPA, PVPB, and PVPC were coating solutions with different PVP contents ranging from 0.1% to 30 wt%.

[0029] Table 1. Water contact angles of uncoated intraocular lenses and intraocular lenses with different functional coatings.

[0030] Intraocular lens samples and lens epithelial cells were co-cultured in 12-well plates, with 10 cells seeded per well. 5 Cells were collected and incubated at 37 ℃ and 5% CO2. Experimental groups included blank intraocular lenses (IOLs), CQDs-PVPA coated IOLs, and CQDs-PVPB coated IOLs. Fresh culture medium was added daily during culture, and assays were performed on days 1, 5, and 10. At each preset time point, IOL samples were removed, gently rinsed with PBS buffer, fixed with 4% paraformaldehyde, and then subjected to a gradient ethanol dehydration treatment. Cell adhesion and growth on the IOL surface were observed using scanning electron microscopy (SEM), and the number of surface cells was counted. Simultaneously, cell viability in the culture supernatant was detected using the CCK-8 assay to evaluate the effect of different coatings on the proliferation behavior of lens epithelial cells. The experimental results are shown in Table 2. Compared with blank intraocular lenses, intraocular lenses with carbon quantum dot nanozyme coatings significantly reduced the adhesion, proliferation and migration of lens epithelial cells and showed good long-term inhibitory effects, indicating that this functionalized coating can effectively reduce the risk of PCO after intraocular lens implantation.

[0031] Table 2. Average number of adherent cells on the surface of different samples

[0032] The above are merely preferred embodiments of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principle of the present invention should be considered within the scope of protection of the present invention.

[0033] Please note to all technical personnel: Although the present invention has been described according to the specific embodiments above, the inventive concept of the present invention is not limited to this invention. Any modifications that utilize the inventive concept will be included within the scope of protection of this patent.

[0034] Please note to all technical personnel: Although the present invention has been described according to the specific embodiments above, the inventive concept of the present invention is not limited to this invention. Any modifications that utilize the inventive concept will be included within the scope of patent protection of this patent.

[0035] The above description is merely a preferred embodiment of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A hydrophilic sustained-release coated intraocular lens loaded with carbon quantum dot nanozymes, characterized in that, A stable carbon quantum dot nanoenzyme sustained-release functional coating is formed on the surface of the artificial lens. The carbon quantum dot nanoenzyme sustained-release functional coating is formed by curing a functional coating liquid composed of biodegradable polymer materials and carbon quantum dot nanoenzymes.

2. The hydrophilic sustained-release coated intraocular lens with carbon quantum dot nanozymes according to claim 1, characterized in that, The carbon quantum dot nanozyme is prepared by hydrothermal reaction, with baicalin as the carbon source and any one or two amino acids as the nitrogen source.

3. The intraocular lens with a hydrophilic sustained-release coating loaded with carbon quantum dot nanozymes according to claim 1, characterized in that, The concentration of carbon quantum dot nanozymes in the functionalized coating solution is 0.5-100 mg / mL.

4. The hydrophilic sustained-release coated intraocular lens with carbon quantum dot nanozymes according to claim 1, characterized in that, The content of biodegradable polymer materials in the functionalized coating liquid is 3-20 wt%.

5. The hydrophilic sustained-release coated intraocular lens with carbon quantum dot nanozymes according to claim 2, characterized in that, The molar ratio of amino acids to baicalin in the carbon quantum dot nanozyme is 0.1:5.0-5.0:0.

1.

6. The hydrophilic sustained-release coated intraocular lens with carbon quantum dot nanozymes according to claim 1, characterized in that, The biodegradable polymer material is one or more of polylactic acid-glycolic acid copolymer (PLGA), polyvinylpyrrolidone (PVP), polyacrylamide (PAM), polyethylene glycol (PEG), and polyvinyl alcohol (PVA).

7. The intraocular lens with a hydrophilic sustained-release coating loaded with carbon quantum dot nanozymes according to claim 1, characterized in that, The carbon quantum dot nanozyme is prepared by the following steps: A carbon source and a nitrogen source were added to a three-necked flask, along with 5-35 mL of a mixed solution of ethanol and deionized water. The mixture was stirred to form a homogeneous solution. The resulting mixed solution was then transferred to a hydrothermal reactor for hydrothermal reaction at a temperature of 100-230ºC for 2-24 h. After dialysis purification, carbon quantum dot nanozymes were obtained. The carbon source was baicalin, and the nitrogen source was any one or two amino acids.

8. The hydrophilic sustained-release coated intraocular lens with carbon quantum dot nanozymes according to claim 7, characterized in that, The volume ratio of ethanol to deionized water is 10:1 to 1:

10.

9. A method for preparing a hydrophilic sustained-release coated intraocular lens with carbon quantum dot nanozymes as described in claim 1, characterized in that, Includes the following steps: (1) Plasma activation treatment of the intraocular lens substrate; (2) Carbon quantum dot nanozymes and biodegradable polymer materials are formulated into a coating liquid, and the coating liquid is applied to the surface of the artificial lens substrate after plasma activation by spin coating. (3) Curing at 20~50℃ for 0.5-24 h forms a stable carbon quantum dot nanoenzyme sustained-release functional coating on the surface of the artificial lens.

10. The preparation method according to claim 9, characterized in that, The plasma activation treatment involves treating the surface of the intraocular lens using a plasma instrument. The oxygen flow rate for the plasma activation treatment is 5-20 cm³ / min, the treatment power is 50-100 W, and the treatment time is 1-6 min.

11. The application of the hydrophilic sustained-release coated intraocular lens with carbon quantum dot nanozymes as described in claim 1 in the preparation of anti-PCO biomaterials.

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