Photothermal "on-off" drug release hydrogel contact lens materials, methods of making and use thereof

Abstract

This invention discloses a method for preparing a photothermal controlled-release hydrogel contact lens material. The method involves chemically bonding ganciclovir with hydroxypropyltrimethylammonium chloride chitosan, then adding methacrylic anhydride to introduce double bonds. The resulting product is used as a crosslinking agent to crosslink and copolymerize with hydroxyethyl methacrylate (MXene) nanosheets to prepare the hydrogel material. The prepared photothermal controlled-release hydrogel contact lens material can bond drugs to the polymer chains of the hydrogel contact lens for drug loading, avoiding drug loss due to tear rinsing, thereby improving drug storage stability. Furthermore, it can be modulated with near-infrared light to generate a photothermal effect, raising the hydrogel temperature and triggering the breakage of thermosensitive azo bonds, releasing the drug into the contact lens matrix. When the lens is worn, the drug can be slowly released from the contact lens into the eye, potentially making it a multifunctional contact lens material for treating eye diseases.

Description

Technical Field

[0001] This invention belongs to the field of medical materials technology, specifically relating to photothermal controlled-release hydrogel corneal contact lens materials, their preparation methods, and applications. Background Technology

[0002] Ophthalmic diseases have become a major social concern, seriously affecting people's health. Currently, eye drops are the simplest treatment for eye diseases, but due to tear flushing and the corneal barrier, only 3%-5% of the drug enters the eye. Most of the drug enters the systemic circulation through the nasal cavity and conjunctiva, resulting in low drug utilization and significant side effects. In recent years, functional contact lenses have received widespread attention as novel ocular surface drug delivery carriers. Hydrogel contact lenses, based on their high adhesion to corneal tissue and ability to regulate drug release kinetics, demonstrate unique advantages in the field of ocular surface drug delivery, including prolonging drug retention time on the cornea, improving local bioavailability, and optimizing patient compliance. Traditional drug delivery methods for contact lenses include immersion loading, nanoparticle loading, molecular imprinting loading, and cyclodextrin loading. Although these methods can slow down the drug release rate to some extent, the drug release cycle remains relatively short, especially failing to achieve on-demand controlled release. Therefore, constructing a smart, responsive "controlled-slow-release" drug delivery system is key to improving the drug delivery efficiency of contact lenses.

[0003] Research indicates that environmental stimuli (such as light, heat, magnetism, pH, and enzymes) can cause changes in the volume, decomposition, or bond breaking of drug-loaded materials, leading to the rapid release of drugs loaded physically or chemically. This technology has been widely applied in the field of anti-tumor nanomedicines. MXenes are a class of two-dimensional layered nanomaterials derived from transition metal carbides or nitrides, with the chemical formula M... n+1 X n T x In this formula, "M" represents a metallic element (mainly transition metals such as chromium, molybdenum, and manganese), "X" represents carbon or nitrogen, and "T" represents functional groups on the material surface (such as hydroxyl and halogen groups). Due to its excellent photothermal conversion properties, this formula is highly favored. Therefore, by using thermosensitive azo groups (thermosensitive temperature approximately 40°C) to bond drugs to the substrate of corneal contact lenses and then doping them with MXene nanosheets, corneal contact lenses with photothermal conversion properties can be fabricated, potentially solving the problem of controlled drug release in corneal contact lenses. Summary of the Invention

[0004] The purpose of this invention is to provide a photothermal controlled-release hydrogel corneal contact lens material and its preparation method, so as to solve the technical problems of premature drug release and insufficient release regulation ability in existing corneal contact lens materials, which result in short drug retention time and greatly limit the treatment of eye diseases.

[0005] A first aspect of the present invention provides a method for preparing a photothermal controlled-release hydrogel corneal contact lens material, comprising the following steps: S1. Dissolve 4,4'-azobis(4-cyanopentanoic acid) (Azo) in a first acidic system. Add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to the first acidic system to activate the carboxyl group. Then add an aqueous solution of hydroxypropyltrimethylammonium chloride chitosan (HACC) to react and purify to obtain the first product. S2. Dissolve the first product in a second acidic system, add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) to the second acidic system and activate the carboxyl group, add an aqueous solution of ganciclovir, react, purify, and obtain the second product. S3. Dissolve the second product in water, then add methacrylic anhydride (MA) to obtain a reaction system. The reaction system is subjected to a pH of 6.5-8.5, purified, and the third product is obtained. S4. Dissolve the third product in water, add hydroxyethyl methacrylate (HEMA) and MXene nanosheets to the water in sequence, then add a photoinitiator to obtain a mixture. Irradiate the mixture under ultraviolet light to purify it, and the product is obtained.

[0006] In this invention, hydroxypropyltrimethylammonium chloride chitosan and ganciclovir are first loaded with the drug via an amidation reaction with 4,4'-azobis(4-cyanopentanoic acid). Then, methacrylic anhydride is added to introduce carbon-carbon double bonds that can copolymerize with hydroxyethyl methacrylate (HEMA), constructing a drug-loaded functional monomer. Finally, the functional monomer is used as a macromolecular crosslinking agent to copolymerize with HEMA, and MXene nanosheets are introduced as a photothermal functional component to construct a photothermally responsive hydrogel material. This hydrogel material covalently bonds drug molecules to the polymer chains of the hydrogel corneal contact lens for drug loading. Under normal circumstances, the chemically bonded drug is not released in the corneal contact lens, avoiding drug loss or shedding due to tear rinsing and improving drug storage stability. During treatment, the drug is released by irradiating the hydrogel material with near-infrared light (NIR), which uses the photothermal effect to raise the temperature of the hydrogel material, thereby triggering the breakage of thermosensitive azo bonds and controlling the release of the drug into the corneal contact lens matrix. Subsequently, the lens is worn, and the drug in the lens is slowly released into the eye, improving drug utilization.

[0007] In some embodiments, the photoinitiator is selected from at least one of 2,2-diethoxyacetophenone, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetophenone, and 2-methyl-1-[4-(methylthio)phenyl]-2-morpholino-1-propanone. Preferably, the photoinitiator is 2,2-diethoxyacetophenone.

[0008] In some embodiments, in step S3, the amount of the third product is 1% to 6% of the total mass of the third product and hydroxyethyl methacrylate. Preferably, the amount of the third product is 2% of the total mass of the third product and hydroxyethyl methacrylate.

[0009] In some embodiments, in step S4, the amount of water used is 30-50% of the total mass of the third product, hydroxyethyl methacrylate, and water. Preferably, the amount of water used is 40% of the total mass of the third product, hydroxyethyl methacrylate, and water.

[0010] In some embodiments, in step S4, the amount of MXene nanosheets used is 0.1 wt‰ to 0.5 wt‰ of the total mass of the third product and hydroxyethyl methacrylate. Preferably, the amount of MXene nanosheets used is 0.35 wt‰ of the total mass of the third product and hydroxyethyl methacrylate.

[0011] In some embodiments, in step S4, the amount of photoinitiator is 0.1% to 1.0% of the total mass of the third product and hydroxyethyl methacrylate. Preferably, the amount of photoinitiator is 0.3% of the total mass of the third product and hydroxyethyl methacrylate. In some embodiments, after 4,4'-azobis(4-cyanopentanoic acid) is dissolved in a first acidic system, the pH value of the first acidic system is 3.0 to 6.5; after the first product is dissolved in a second acidic system, the pH value of the second acidic system is 3.0 to 6.5. Preferably, after the first product is dissolved in the second acidic system, the pH value of the second acidic system is 5 to 6.

[0012] In some embodiments, the pH of the first acidic system after 4,4'-azobis(4-cyanopentanoic acid) is dissolved in the first acidic system and the second acidic system after the first product is dissolved in the second acidic system can be adjusted with acetic acid.

[0013] In some embodiments, the first acidic system and the second acidic system are acetic acid.

[0014] In some embodiments, in step S1, the carboxyl group is activated by stirring at 0-10°C in the dark for 20-40 minutes.

[0015] In some embodiments, in step S1, the molar ratio of carboxyl groups in 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and 4,4'-azobis(4-cyanopentanoic acid) is (1~10):(1~10):1. Preferably, the molar ratio of carboxyl groups in 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and 4,4'-azobis(4-cyanopentanoic acid) is 3:3:1.

[0016] In some embodiments, in step S1, the molar ratio of the amino group of hydroxypropyltrimethylammonium chloride chitosan to 4,4'-azobis(4-cyanopentanoic acid) is 1:0.1 to 1:10.

[0017] In some embodiments, the reaction time in step S1 is 4 to 48 hours. Preferably, the reaction time is 24 hours.

[0018] In some embodiments, in step S2, the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and the carboxyl group in the first product is (1~10):(1~10):1. Preferably, the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and the carboxyl group in the first product is 3:3:1.

[0019] In some embodiments, the method for activating the carboxyl group in step S2 is to stir at 0-8°C in the dark for 20-40 minutes.

[0020] In some embodiments, in step S2, the molar ratio of the carboxyl group of the first product to ganciclovir is 1:1 to 1:4.

[0021] In some embodiments, the reaction time in step S2 is 4 to 48 hours. Preferably, the reaction time is 24 hours.

[0022] In some embodiments, step S3 is carried out at 0-8°C in the dark.

[0023] In some embodiments, in step S3, the molar ratio of the second product to methacrylic anhydride is 1:1 to 1:9. Preferably, the molar ratio of the second product to methacrylic anhydride is 1:1.5.

[0024] In some implementations, in step S3, the pH value is adjusted using NaOH.

[0025] In some embodiments, the reaction time in step S3 is 4 to 48 hours. Preferably, the reaction time is 24 hours.

[0026] In some embodiments, the irradiation time in step S4 is 10-30 minutes. Preferably, the irradiation time is 20 minutes. If the irradiation time is too short, the hydrogel material cannot be photocured; if the irradiation time is too long, the hydrogel will heat up due to the energy generated by the ultraviolet lamp, and the azo bonds may break prematurely.

[0027] In some embodiments, the purification method in steps S1, S2, and S3 involves dialysis to obtain a retention solution, with the dialysis bag used having a molecular weight cutoff of 8000 Da. The purpose of dialysis is to remove small molecules (such as acetic acid, EDC, NHS, AZo, and GVC).

[0028] In some embodiments, MXene nanosheets are prepared by the following steps: Lithium fluoride (LiF) was mixed with hydrochloric acid solution, and Ti3AlC2 was added. The mixture was then stirred to complete the etching of the Al layer and obtain a suspension. The suspension was centrifuged and the precipitate was washed until the pH of the supernatant was 6.5-7.5. Then, the precipitate was dispersed in deionized water, sonicated under an inert atmosphere, centrifuged, and the supernatant was collected to obtain a suspension of MXene nanosheets. The suspension was then freeze-dried to obtain the final product.

[0029] In some embodiments, the concentration of the hydrochloric acid solution is 6-12 mol / L. Preferably, the concentration of the hydrochloric acid solution is 9 mol / L.

[0030] In some embodiments, the stirring temperature is 30~45°C and the stirring time is 4~48 h. Preferably, the stirring temperature is 35°C and the stirring time is 36 h.

[0031] In some embodiments, the inert atmosphere is selected from at least one of N2, Ar, and He. Preferably, the inert atmosphere is N2.

[0032] In some embodiments, the ultrasound time is 20 to 40 minutes. Preferably, the ultrasound time is 30 minutes.

[0033] According to a second aspect of the present invention, a photothermal controlled-release hydrogel corneal contact lens material prepared by the above-described preparation method is provided.

[0034] The photothermal controlled-release hydrogel contact lens material of this invention covalently bonds ganciclovir molecules to the polymer chain of the hydrogel contact lens through chemical bonding, ensuring that the drug molecules are not easily washed away or detached by tear fluid, thereby achieving long-term drug storage in the contact lens. Simultaneously, the introduction of MXene nanosheets into the hydrogel matrix endows the material with highly efficient near-infrared (NIR) thermal conversion capabilities, thus giving the photothermal controlled-release hydrogel contact lens material the ability to control the slow release of the drug under near-infrared light.

[0035] According to a third aspect of the invention, the use of a photothermal controlled-release hydrogel corneal contact lens material in the preparation of materials for treating eye diseases is provided.

[0036] In some implementations, the eye disease is a viral infection of the eye, such as herpes simplex keratitis or herpes zoster keratitis.

[0037] The photothermal controlled-release hydrogel corneal contact lens material of the present invention not only effectively stores drugs, but also utilizes the photothermal effect to control the release of drugs on demand, prolonging the time the drugs remain in the eyeball, and realizing controlled-release drug treatment. This has important significance and application prospects for improving the treatment effect of ophthalmic diseases.

[0038] The beneficial effects of this invention are as follows: (1) The preparation method of the photothermal "controlled-slow" release drug hydrogel corneal contact lens material provided by the present invention is simple, has good repeatability and strong operability.

[0039] (2) The photothermal controlled-release hydrogel contact lens material prepared in this invention uses HACC, which has excellent hydrophilicity and antibacterial properties, as the molecular backbone. It is chemically coupled with thermosensitive azo dyes and the drug molecule ganciclovir, and then functionalized with MA to create a functional monomer with both thermosensitive drug release and photocuring functions. Subsequently, the functional monomer is used as a crosslinking agent to copolymerize with HEMA, and MXene nanosheets are introduced as a photothermal functional component to prepare a photothermal responsive hydrogel material. This improves upon the shortcomings of poor drug storage stability and insufficient release regulation in hydrogels, prolonging the drug retention time in the eye, and is expected to become a multifunctional contact lens material for the treatment of eye diseases. Attached Figure Description

[0040] Figure 1 This is a schematic diagram of the process flow for p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel materials; Figure 2 FT-IR images of MA, GCV, HACC-Azo, HACC-Azo-GCV and mHACC-Azo-GCV; Figure 3 For HACC, HACC-Azo, HACC-Azo-GCV and mHACC-Azo-GCV 1 H NMR spectrum; Figure 4 (a) is a SEM image of MXene nanosheets; Figure 4 (b) is a TEM image of MXene nanosheets; Figure 5XRD patterns of Ti3AlC2, neutral products, and MXene nanosheets; Figure 6 FT-IR images and magnified FT-IR plots of p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel, pHEMA hydrogel, mHACC-Azo-GCV, and HEMA; Figure 7 The equilibrium water content test results for different hydrogel materials; Figure 8 Results of surface water contact angle tests for different hydrogel materials; Figure 9 (a) shows the stress-strain curves of different hydrogel materials; Figure 9 (b) Tensile strength of different hydrogel materials; Figure 9 (c) represents the tensile modulus of different hydrogel materials; Figure 9 (d) represents the elongation at break of different hydrogel materials; Figure 10 (a) Time-temperature curves of different hydrogel materials at different powers; Figure 10 (b) Thermal images of different hydrogel materials reaching their highest temperatures at different powers; Figure 10 (c) is the photo-thermal cycling response diagram of the p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material prepared in Example 1 under 1.0 W near-infrared light irradiation; Figure 11 (a) Drug release curves of different hydrogel materials after irradiation with 1.0 W near-infrared light for 5 min; Figure 11 (b) Drug release curves of the p(HEMA-co-mHACC-Azo) / MXene hydrogel material prepared in Example 1 after irradiation with 1.0 W near-infrared light for different durations; Figure 11 (c) Drug release curves of the p(HEMA-co-mHACC-Azo) / MXene hydrogel material prepared in Example 1 under "on / off" periodic irradiation; Figure 11 (d) Drug release rate of the p(HEMA-co-mHACC-Azo) / MXene hydrogel material prepared in Example 1 under "on / off" periodic irradiation. Detailed Implementation

[0041] The present invention will now be described in further detail with reference to the accompanying drawings, but the embodiments of the present invention are not limited thereto. The raw materials and reagents involved in the following embodiments are all commercially available.

[0042] The present invention discloses a method for preparing a photothermal controlled-release drug-eluting hydrogel contact lens material. Using HACC, a hydrophilic and antibacterial compound with excellent properties, as the molecular framework, the method first involves amidation of one carboxyl hydroxyl group of the azo molecule 4,4'-azobis(4-cyanopentanoic acid) (Azo) with the amino group of hydroxypropyltrimethylammonium chloride chitosan (HACC) to obtain HACC-Azo. Then, utilizing the amino group of the drug molecule ganciclovir (GVC), an amidation reaction can occur with the other carboxyl hydroxyl group of HACC-Azo, thereby achieving chemical coupling of the thermosensitive azo and the drug molecule. Next, methacrylic anhydride (MA) reacts with some hydroxyl groups of HACC (mainly the -OH group at position 6) to generate ester groups, thereby achieving double bond functionalization modification to obtain mHACC-Azo-GCV. Then, mHACC-Azo-GCV is used as a crosslinking agent and crosslinked and copolymerized with HEMA under the action of a photoinitiator, while simultaneously doping with MXene nanosheets. The process flow is as follows: Figure 1 As shown.

[0043] It should be noted that in the preparation method of the present invention, since MA also reacts with the amino group of HACC, if the step of reacting methacrylic anhydride (MA) with HACC occurs before the amidation reaction of Azo with HACC, the resulting product will not have an amino group that can react with Azo. Therefore, the steps in the preparation method of the present invention are selected to achieve the bonding between HACC and Azo.

[0044] To enable the two terminal carboxyl hydroxyl groups of Azo to react with HACC and GVC, the raw materials are added to an acidic system for two reactions, and the carboxyl groups are activated by NHS and EDC.

[0045] Commercially available MXene nanosheets can also be used to dope them into the mHACC-Azo-GCV of this invention.

[0046] Example 1 This embodiment provides a method for preparing a photothermal controlled-release drug-eluting hydrogel corneal contact lens material (p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material), comprising the following steps: (1) Dissolve 1.88 g of Azo in acetic acid (pH = 5-6 after dissolution), add 3.86 g of EDC and 2.31 g of NHS, making the molar ratio of EDC, NHS and Azo carboxyl groups (-COOH) 3:3:1. Stir at 4°C in the dark for 30 min to activate the carboxyl groups. Separately, weigh 1 g of HACC, dissolve it completely in deionized water, and slowly add it to the above solution. Stir at 4°C in the dark for 24 h. After the reaction is complete, pour the solution into a dialysis bag (molecular weight cutoff of 8000 Da) for purification. Freeze-dry the purified retentate to obtain HACC-Azo.

[0047] 1 g of HACC-Azo was dissolved in acetic acid (pH 5-6 after dissolution), and 1 g of EDC and 0.59 g of NHS were added to achieve a molar ratio of 3:3:1 for the carboxyl groups (-COOH) in EDC, NHS, and HACC-Azo. The mixture was stirred in the dark at 4°C for 30 min to activate the carboxyl groups. 0.88 g of GCV was dissolved in deionized water and slowly added to the HACC-Azo solution. The mixture was stirred in the dark at 4°C for 24 h. After the reaction, the solution was transferred to a dialysis bag (molecular weight cutoff 8000 Da) for purification. The purified retentate was freeze-dried to obtain HACC-Azo-GCV.

[0048] 1 g of HACC-Azo-GCV and 65.6 g of ultrapure water (to prepare a 1.5 wt% HACC-Azo-GCV solution) were added to a beaker, and the mixture was stirred at 4 °C for 4 h. After the HACC-Azo-GCV was completely dissolved, 0.28 g of MA was added dropwise to the beaker and stirred in the dark for 30 min. After the system was homogeneous, the pH of the system was adjusted to 7-8 with 1 mol / L NaOH solution, and then stirred for another 24 h in the dark. After the reaction was complete, the solution was transferred to a dialysis bag (molecular weight cutoff of 8000 Da) for purification. The purified retentate was freeze-dried to obtain mHACC-Azo-GCV.

[0049] (2) 2.0 g of lithium fluoride (LiF) powder was mixed with 40 mL of 9 mol / L hydrochloric acid solution and magnetically stirred until completely dissolved. Then, 2.0 g of Ti3AlC2 powder was added, and the mixture was magnetically stirred at 35 °C for 36 h to complete the etching of the Al layer. After centrifugation of the obtained suspension, the supernatant was removed. The precipitate was centrifuged and washed repeatedly with deionized water until the pH of the supernatant was 7.0. Then, the neutral product was dispersed in deionized water and ultrasonically exfoliated for 30 min under an inert atmosphere of N2. After centrifugation, the supernatant was collected to obtain a suspension of MXene nanosheets. The suspension was freeze-dried to obtain MXene nanosheets.

[0050] (3) Weigh 0.1 g mHACC-Azo-GCV and dissolve it in 3 mL of deionized water, then add 4.9 g HEMA monomer. After stirring the mixture magnetically for 4 h at 4 °C in the dark, add 1 mL of MXene nanosheet aqueous suspension with a concentration of 1.75 mg / mL (mass fraction of 0.35‰) and stir until uniformly dispersed. Further add the photoinitiator 2,2-diethoxyacetophenone (0.3% of the total mass of mHACC-Azo-GCV and HEMA), and stir in the dark for 30 min until the system is homogeneous. Inject the resulting mixture into a mold consisting of two glass plates and a silicone gasket, and irradiate it under ultraviolet light for 20 min to obtain the crude hydrogel product. After purification by soaking in deionized water, p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material is obtained.

[0051] The method for preparing the MXene nanosheet aqueous suspension involves dispersing MXene nanosheets in water. The reason for preparing the MXene nanosheets as a suspension before adding them is that MXene nanosheets have a small mass and are difficult to weigh accurately. Preparing a suspension of the appropriate concentration first, and then adding the corresponding volume of suspension to the system, allows for more accurate measurement of the amount of MXene nanosheets added.

[0052] MA, GCV, HACC-Azo, HACC-Azo-GCV, and mHACC-Azo-GCV were characterized by FT-IR, and the results are as follows: Figure 2 As shown. From Figure 2 It can be seen that HACC-Azo at 1650 cm -1 (C=O stretching vibration absorption, amide I band) and 1570 cm -1 The characteristic absorption peak at (NH bending vibration absorption, amide II band) indicates that HACC has successfully undergone an amidation reaction with Azo, forming an amide bond (-CONH-). The HACC-Azo-GCV peak appears at 1740 cm⁻¹. -1 The characteristic absorption peak at 1650 cm⁻¹ disappears, and at 1650 cm⁻¹... -1 and 1570 cm -1 The increased absorption peak intensity at 1780 cm⁻¹ indicates that the reaction between HACC-Azo and GCV consumes the -COOH group on Azo, generating -CONH-. MA at 1780 cm⁻¹ -1 and 1720 cm -1 The disappearance of the characteristic peak of the anhydride group at the site indicates that MA successfully reacted with the -OH group of HACC. These results demonstrate the successful synthesis of HACC-Azo, HACC-Azo-GCV, and mHACC-Azo-GCV.

[0053] Perform HACC, HACC-Azo, HACC-Azo-GCV and mHACC-Azo-GCV respectively 1 H NMR characterization, results as follows Figure 3 As shown. From Figure 3 As can be seen, HACC-Azo exhibits multiple peaks at 1.63-1.72 ppm and 2.25-2.45 ppm, corresponding to the H-4 methyl and H-5 methylene groups of Azo, respectively, indicating that HACC and Azo have successfully reacted. HACC-Azo-GCV and mHACC-Azo-GCV show an absorption peak for the H-6 methylene proton of GCV at 1.20 ppm, indicating that GCV has successfully bonded to HACC-Azo. mHACC-Azo-GCV shows the H-8 proton on the unsaturated carbon-carbon double bond of MA at 5.65 ppm and 5.25 ppm, and an absorption peak for the H-7 proton of MA at 1.79 ppm, indicating that MA has successfully bonded to the HACC molecular chain. Therefore, Example 1 successfully prepared mHACC-Azo-GCV.

[0054] The MXene nanosheets were characterized by SEM and TEM, and the results are as follows: Figure 4 As shown. Figure 4 The SEM and TEM images reveal a significant evolution in the morphology of MXene materials: after etching, MXene nanosheets exhibit a typical two-dimensional layered morphology, with significant dissociation and expansion between the layers due to the removal of the Al layer, forming a loose layered structure.

[0055] The Ti3AlC2, neutral product (Multilayer MXene), and MXene nanosheets (Few-layer MXene) from step (2) of Example 1 were characterized by XRD, and the results are as follows: Figure 5 As shown. By Figure 5 It can be seen that the etched MXene nanosheets have diffraction peaks at 2θ≈34.3°, 39.3°, and 42°, which have disappeared, confirming that the Al atomic layer has been effectively removed by chemical etching. The diffraction peaks of Ti3AlC2 at 9.8° and 19.4° have shifted to lower angles to 6.4° and 17.9°, respectively. This change in XRD characteristics is consistent with the crystal structure evolution of typical MXene materials.

[0056] Figure 4 and Figure 5 The results show that few-layer MXene nanosheets were successfully prepared.

[0057] Comparative Example 1 This comparative example provides a method for preparing pHEMA hydrogel. The difference from Example 1 is that mHACC-Azo-GCV is replaced with ethylene glycol dimethacrylate, and 1 mL of MXene nanosheet aqueous suspension with a concentration of 1.75 mg is not added.

[0058] The p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material prepared in Example 1, the pHEMA hydrogel, mHACC-Azo-GCV, and HEMA monomer prepared in Comparative Example 1 were characterized by FT-IR, and the results are as follows: Figure 6 As shown. From Figure 6 It can be seen that in the copolymer p(HEMA-co-mHACC-Azo-GCV) spectrum, the HEMA monomer is at 1635 cm⁻¹. -1 The disappearance of the characteristic absorption peak signal of the C=C double bond at this point indicates that the double bond has participated in the polymerization reaction. Meanwhile, the copolymer spectrum at 1650 cm⁻¹... -1 and 1570cm -1 The presence of characteristic peaks for the C=O stretching vibration and NH bending vibration of the amide group in the mHACC-Azo-GCV functional monomer at the specified locations confirms the successful copolymerization and crosslinking of HEMA and the mHACC-Azo-GCV monomer. These results indicate the successful preparation of the p(HEMA-co-mHACC-Azo-GCV) hydrogel material.

[0059] Comparative Example 2 This comparative example provides a method for preparing a hydrogel corneal contact lens material. The difference from Example 1 is that, in step (3), 1 mL of an aqueous suspension of MXene nanosheets with a concentration of 1.75 mg / mL is not added. The prepared hydrogel corneal contact lens material is denoted as 0wt‰MXene.

[0060] Example 2 This embodiment provides a method for preparing a photothermal controlled-release hydrogel corneal contact lens material. The difference from Example 1 is that in step (3), 1 mL of an aqueous suspension of MXene nanosheets with a concentration of 0.75 mg / mL is added. The prepared photothermal controlled-release hydrogel corneal contact lens material is denoted as 0.15 wt‰ MXene.

[0061] Example 3 This embodiment provides a method for preparing a photothermal controlled-release hydrogel corneal contact lens material. The difference from Example 1 is that in step (3), 1 mL of an aqueous suspension of MXene nanosheets with a concentration of 1.25 mg / mL is added. The prepared photothermal controlled-release hydrogel corneal contact lens material is denoted as 0.25 wt‰ MXene.

[0062] Experimental Example 1 In this experiment, the photothermal controlled-release hydrogel corneal contact lens material prepared in Example 1 (denoted as 0.35wt‰MXene), the photothermal controlled-release hydrogel corneal contact lens material prepared in Examples 2-3, the pHEMA hydrogel material prepared in Comparative Example 1, and the hydrogel material prepared in Comparative Example 2 were used as samples for testing of equilibrium water content, surface water contact angle, and mechanical properties.

[0063] (1) Equilibrium moisture content test Each sample was immersed in deionized water for 48 hours to reach swelling equilibrium. The surface moisture was then wiped off with lint-free paper, and the mass at swelling equilibrium was measured as m0. The material was then dried in a 60°C oven until its mass no longer changed, and the mass at the dried state was measured as m. dry The equilibrium water content is calculated using equation ①: EWC= Formula ①.

[0064] The equilibrium moisture content calculation results for each sample are as follows: Figure 7 As shown, from Figure 7 It can be seen that the equilibrium water content of the hydrogel material containing the crosslinking agent mHACC-Azo-GCV is significantly higher than that of the pHEMA hydrogel, indicating that the introduction of mHACC-Azo-GCV into the pHEMA matrix can improve the water content of the corneal contact lens material. This may be attributed to the extremely strong hydrophilicity of the HACC molecule itself. The amount of MXene used has no significant effect on the equilibrium water content of the photothermal controlled-release hydrogel corneal contact lens material.

[0065] (2) Surface water contact angle test Each sample in swelling equilibrium was attached to a glass slide, and then 5 μL of water was dropped onto the surface of the hydrogel and photographed immediately. The surface water contact angle was measured from the water drop photograph.

[0066] The surface water contact angle test results of each sample are as follows: Figure 8 As shown. From Figure 8 It can be seen that the water contact angle of the hydrogel material containing mHACC-Azo-GCV is lower than that of the pHEMA hydrogel. The water contact angle of the hydrogel material containing both mHACC-Azo-GCV and MXene is significantly reduced compared to the hydrogel material containing only mHACC-Azo-GCV, and it decreases with increasing MXene content. This indicates that the simultaneous introduction of HACC and MXene into the pHEMA matrix can improve the hydrophilicity of the corneal contact lens material.

[0067] (3) Mechanical property testing After cutting each sample to its swelling equilibrium state, the samples were mounted on a general testing machine, and the mechanical properties of the material were measured at a tensile speed of 50 mm / min.

[0068] The mechanical property test results of each sample are as follows: Figure 9 As shown. Figure 9 (a) shows the stress-strain curves of different hydrogel materials; Figure 9 (b) represents the tensile strength of different hydrogel materials, where the value is the stress at tensile fracture, i.e. Figure 9 (a) Stress at maximum strain; Figure 9 (c) represents the tensile modulus of different hydrogel materials, with values ​​of [value missing]. Figure 9 (a) Slope of strain 1%-10%; Figure 9 (d) represents the elongation at break of different hydrogel materials. Figure 9 (b) It can be seen that the tensile strength of the hydrogel material containing mHACC-Azo-GCV is higher than that of the pHEMA hydrogel material. This indicates that mHACC-Azo-GCV, as a macromolecular crosslinking agent, has randomly arranged and entangled chain segments in water, and has multiple crosslinking points with pHEMA. When subjected to tensile stress, mHACC-Azo-GCV can uniformly distribute the stress to various parts of the hydrogel material, and dissipate energy through deentanglement, thus improving the tensile properties of the hydrogel material. Figure 9 (d) It can be seen that the elongation at break of the hydrogel material containing mHACC-Azo-GCV is significantly higher than that of the pHEMA hydrogel material, indicating that the introduction of mHACC-Azo-GCV also improves the elongation at break. Furthermore, the elongation at break decreases with increasing MXene content. This may be because MXene is rich in metal elements and surface hydrophilic groups (such as carbonyl, hydroxyl, and fluorine), which can form hydrogen bonds with the hydrophilic groups of pHEMA and mHACC-Azo-GCV, creating physical cross-linking points and thus increasing the tensile strength of the hydrogel material. However, MXene is a rigid two-dimensional layered material. Under tensile stress, its edges contact the hydrogel network, easily generating stress concentration, leading to network fracture and microcracks, which in turn reduces the elongation at break of the hydrogel material. These results demonstrate that introducing HACC and MXene into the pHEMA matrix can significantly enhance flexibility and is beneficial for suppressing the brittle fracture behavior of corneal contact lenses.

[0069] Experiment Example 2 In this experiment, the photothermal controlled-release hydrogel corneal contact lens material (0.35wt‰MXene) prepared in Example 1, the photothermal controlled-release hydrogel corneal contact lens materials prepared in Examples 2-3, and the hydrogel material prepared in Comparative Example 2 were tested for photothermal properties.

[0070] Sample preparation method: Each hydrogel material was immersed in deionized water for 48 h to reach swelling equilibrium. Then, the surface moisture of the material was wiped off with lint-free paper to obtain each sample in swelling equilibrium.

[0071] Each sample was cut into cylindrical slices with a diameter of 6 mm and a thickness of 0.3 mm. Deionized water was added to keep the slices wettable. Then, a near-infrared laser was fixed 5 cm above the slices to irradiate them. The temperature of the slices was recorded using an infrared thermal imager at a frequency of 1 second / time to obtain the photothermal properties of the material.

[0072] The photothermal properties of different hydrogel materials are as follows: Figure 10 As shown, where, Figure 10 (a) Time-temperature curves of different hydrogel materials at different powers; Figure 10 (b) Thermal images of different hydrogel materials reaching their highest temperatures at different powers; Figure 10 (c) is the photo-thermal cycling response diagram of the p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material prepared in Example 1 under 1.0 W near-infrared light irradiation. Figure 10 As can be seen from (a) and (b), the temperature of 0 wt% MXene remained essentially unchanged from 0 to 420 s, while the p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel materials of Examples 1-3 showed greater temperature changes from 0 to 420 s. Furthermore, the temperature rise of the p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel materials increased with increasing MXene content or near-infrared light power. Figure 10 (c) It can be seen that the temperature change curves of 0.35wt‰MXene under repeated irradiation with 1.0 W near-red light are basically consistent. This indicates that the p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material exhibits good photothermal heating rate and photothermal cycling stability, suggesting that this hydrogel material has great potential in the field of photothermal controlled-release drug treatment for eye diseases.

[0073] Comparative Example 3 This comparative example provides a method for preparing p(HEMA-co-mHACC-Azo) / MXene hydrogel materials. The difference from Example 1 is that GVC is not added.

[0074] Experimental Example 3 In this experiment, the photothermal controlled-release hydrogel corneal contact lens material (0.35wt‰MXene) prepared in Example 1, the photothermal controlled-release hydrogel corneal contact lens material prepared in Examples 2-3, and the hydrogel material prepared in Comparative Example 2 were subjected to drug release experiments.

[0075] Sample preparation method: Each hydrogel material was immersed in deionized water for 48 h to reach swelling equilibrium. Then, the surface moisture of the material was wiped off with lint-free paper to obtain each sample in swelling equilibrium.

[0076] Each sample was cut into cylindrical slices with a diameter of 6 mm and a thickness of 0.3 mm, and placed in PBS solution of V0 = 0.4 mL. A near-infrared laser was then fixed 5 cm above the slices and irradiated for different times (0, 1, 3, 5, 7 min), after which irradiation was stopped. At certain time intervals, V1 = 0.2 mL of PBS solution was removed, and 0.2 mL of fresh PBS solution was immediately added. The characteristic UV absorption peak at 194 nm of each sample was measured, and the GCV concentration C of the i-th sample was obtained using a concentration-absorption peak standard curve of GCV. i Take another thin film of the same size, release it at 80℃ for 48 h, collect the drug solution, and calculate the total GCV content m of the hydrogel. The cumulative GCV release rate is obtained using equation ②: Cumulative release rate = Equation ②.

[0077] As a control, the ungrafted p(HEMA-co-mHACC-Azo) / MXene hydrogel material prepared in Comparative Example 3 was loaded with drug by a physical adsorption method of freeze-drying and soaking in concentrated GCV solution for 48 h, without being irradiated with near-infrared light, and the cumulative release rate was calculated using the same method.

[0078] Drug release behavior of different hydrogel materials, such as Figure 11 As shown, Figure 11 (a) Drug release curves of different hydrogel materials after irradiation with 1.0 W near-infrared light for 5 min; Figure 11 (b) Drug release curves of the p(HEMA-co-mHACC-Azo) / MXene hydrogel material prepared in Example 1 after irradiation with 1.0 W near-infrared light for different durations; Figure 11 (c) Drug release curves of the p(HEMA-co-mHACC-Azo) / MXene hydrogel material prepared in Example 1 under "on / off" periodic irradiation; Figure 11 (d) Drug release rate of the p(HEMA-co-mHACC-Azo) / MXene hydrogel material prepared in Example 1 under "on / off" periodic irradiation. Figure 11(a) It can be seen that after near-infrared light irradiation at different times, the cumulative release rate of the MXene-containing hydrogel material was higher than that of the MXene-free hydrogel material. This indicates that the p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material can control drug release through photothermal heating and thermally triggered azo bond breakage, and the cumulative drug release rate increases with the increase of MXene content. Moreover, the cumulative release rate of the MXene-containing hydrogel material gradually increases in the first 0-4 hours, indicating that the drug in the MXene-containing hydrogel material is slowly released during this time range, suggesting that the p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material has the potential to prolong the drug release cycle.

[0079] from Figure 11 (b) It can be seen that with the increase of near-infrared light irradiation time, the cumulative release rate of the p(HEMA-co-mHACC-Azo) / MXene hydrogel material with an MXene content of 0.35 wt‰ increases. This may be because the longer the near-infrared light irradiation time, the more obvious the photothermal effect of the MXene nanosheets, triggering more thermosensitive azo bond breakage. The hydrogel material was subjected to "on-off" periodic irradiation. Specifically, the GCV release was measured after irradiating the sample for 30 min, which is the "on" process in one cycle. Then, fresh PBS was added, and the GCV release was measured again after 30 min as a control, which is the "off" process in one cycle. The results are as follows. Figure 11 As shown in (c) and (d). From Figure 11 (c) and Figure 11 (d) It can be seen that the initial release rates of the p(HEMA-co-mHACC-Azo) / MXene hydrogel material at 1, 3, 5, and 7 minutes of initial irradiation were 2.0%, 3.2%, 6.6%, and 10.7%, respectively. After 10 irradiation cycles, the cumulative release rates of the hydrogel material at 1, 3, 5, and 7 minutes of irradiation were 21.6%, 35.6%, 55.7%, and 78.6%, respectively. The thermosensitive controlled-release of the drug after multiple on-off irradiations with near-infrared light indicates that the hydrogel material can deliver the drug multiple times as needed, demonstrating controllability and long-lasting effect. In contrast, the physical adsorption drug delivery method used as a control showed that approximately 85% of GCV was released after 2 hours, indicating that chemically binding GCV to HACC-Azo is beneficial for controlling the slow release of GVC.

[0080] Example 4 This embodiment provides a method for preparing a photothermal controlled-release drug-eluting hydrogel corneal contact lens material (p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material), comprising the following steps: (1) Dissolve 1.88 g of Azo in acetic acid (pH = 3-4 after dissolution), add 1.29 g of EDC and 0.77 g of NHS to make the molar ratio of EDC, NHS and Azo carboxyl groups (-COOH) 1:1:1. Stir at 4°C in the dark for 20 min to activate the carboxyl groups. Separately, weigh 1 g of HACC, dissolve it completely in deionized water, and slowly add it to the above solution. Stir at 4°C in the dark for 4 h. After the reaction is complete, pour the solution into a dialysis bag (molecular weight cutoff of 8000 Da) for purification. Freeze-dry the purified retentate to obtain HACC-Azo.

[0081] 1 g of HACC-Azo was dissolved in acetic acid (pH = 3-4 after dissolution), and 0.33 g of EDC and 0.20 g of NHS were added to make the molar ratio of EDC, NHS, and carboxyl groups (-COOH) in HACC-Azo 1:1:1. The mixture was stirred in the dark at 4 °C for 20 min to activate the carboxyl groups. 0.88 g of GCV was dissolved in deionized water and slowly added to the HACC-Azo solution. The mixture was stirred in the dark at 4 °C for 4 h. After the reaction was completed, the solution was transferred to a dialysis bag (molecular weight cutoff of 8000 Da) for purification. The purified retentate was freeze-dried to obtain HACC-Azo-GCV.

[0082] 1 g of HACC-Azo-GCV and 66.6 g of ultrapure water (to prepare a 1.5 wt% HACC-Azo-GCV solution) were added to a beaker, and the mixture was stirred at 4 °C for 4 h. After the HACC-Azo-GCV was completely dissolved, 0.18 g of MA was added dropwise to the beaker and stirred in the dark for 30 min. After the system was homogeneous, the pH of the system was adjusted to 6.5–7.0 with 1 mol / L NaOH solution, and then stirred for another 4 h in the dark. After the reaction was complete, the solution was transferred to a dialysis bag (with a molecular weight cutoff of 8000 Da) for purification. The purified retentate was freeze-dried to obtain mHACC-Azo-GCV.

[0083] (2) 2.0 g of lithium fluoride (LiF) powder was mixed with 40 mL of 6 mol / L hydrochloric acid solution and magnetically stirred until completely dissolved. Then, 2.0 g of Ti3AlC2 powder was added, and the mixture was magnetically stirred at 30 °C for 48 h to complete the etching of the Al layer. After centrifugation of the obtained suspension, the supernatant was removed. The precipitate was centrifuged and washed repeatedly with deionized water until the pH of the supernatant was 7.0. Then, the neutral product was dispersed in deionized water and ultrasonically exfoliated for 40 min under an inert atmosphere of N2. After centrifugation, the supernatant was collected to obtain a suspension of MXene nanosheets. The suspension was freeze-dried to obtain MXene nanosheets.

[0084] (3) Weigh 0.05 g mHACC-Azo-GCV and dissolve it in 2.14 mL of deionized water, then add 4.95 g HEMA monomer. After stirring the mixture magnetically for 4 h at 4℃ in the dark, add 1 mL of MXene nanosheet aqueous suspension with a concentration of 0.5 mg / mL (mass fraction of 0.10‰) and stir until uniformly dispersed. Further add the photoinitiator 2,2-diethoxyacetophenone (0.1% of the total mass of mHACC-Azo-GCV and HEMA), and stir in the dark for 30 min until the system is homogeneous. Inject the resulting mixture into a mold consisting of two glass plates and a silicone gasket, and irradiate it under ultraviolet light for 10 min to obtain the crude hydrogel product. After purification by soaking in deionized water, p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material is obtained.

[0085] The p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material prepared in Example 4 was characterized by FT-IR. The obtained infrared spectrum curve was similar to that of Example 1, indicating that the hydrogel material was successfully synthesized by the preparation method of Example 4.

[0086] Example 5 This embodiment provides a method for preparing a photothermal controlled-release drug-eluting hydrogel corneal contact lens material (p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material), comprising the following steps: (1) Dissolve 1.88 g of Azo in acetic acid (pH of the dissolved system = 6~6.5), add 12.86 g of EDC and 7.72 g of NHS, so that the molar ratio of carboxyl groups (-COOH) in EDC, NHS and Azo is 10:10:1. Stir at 4℃ in the dark for 40 min to activate the carboxyl groups. Separately, weigh 1 g of HACC, dissolve it completely in deionized water, and slowly add it to the above solution. Stir at 10℃ in the dark for 36 h. After the reaction is complete, pour the solution into a dialysis bag (molecular weight cutoff of 8000 Da) for purification. Freeze-dry the purified retentate to obtain HACC-Azo.

[0087] 1 g of HACC-Azo was dissolved in acetic acid (pH = 6-6.5 after dissolution), and 3.32 g of EDC and 1.98 g of NHS were added to make the molar ratio of EDC, NHS, and HACC-Azo carboxyl groups (-COOH) 10:10:1. The mixture was stirred in the dark at 4 °C for 40 min to activate the carboxyl groups. 0.88 g of GCV was dissolved in deionized water and slowly added to the HACC-Azo solution. The mixture was stirred in the dark at 10 °C for 36 h. After the reaction was completed, the solution was transferred to a dialysis bag (molecular weight cutoff of 8000 Da) for purification. The purified retentate was freeze-dried to obtain HACC-Azo-GCV.

[0088] 1 g of HACC-Azo-GCV and 66.6 g of ultrapure water (to prepare a 1.5 wt% HACC-Azo-GCV solution) were added to a beaker, and the mixture was stirred at 4 °C for 4 h. After the HACC-Azo-GCV was completely dissolved, 0.55 g of MA was added dropwise to the beaker and stirred in the dark for 30 min. After the system was homogeneous, the pH of the system was adjusted to 8–8.5 with 1 mol / L NaOH solution, and then stirred for another 36 h in the dark. After the reaction was complete, the solution was transferred to a dialysis bag (molecular weight cutoff of 8000 Da) for purification. The purified retentate was freeze-dried to obtain mHACC-Azo-GCV.

[0089] (2) 2.0 g of lithium fluoride (LiF) powder was mixed with 40 mL of 12 mol / L hydrochloric acid solution and magnetically stirred until completely dissolved. Then, 2.0 g of Ti3AlC2 powder was added, and the mixture was magnetically stirred at 45 °C for 24 h to complete the etching of the Al layer. After centrifugation of the obtained suspension, the supernatant was removed. The precipitate was centrifuged and washed repeatedly with deionized water until the pH of the supernatant was 7.0. Then, the neutral product was dispersed in deionized water and ultrasonically exfoliated for 40 min under an inert atmosphere of N2. After centrifugation, the supernatant was collected to obtain a suspension of MXene nanosheets. The suspension was freeze-dried to obtain MXene nanosheets.

[0090] (3) Weigh 0.3 g of mHACC-Azo-GCV and dissolve it in 3 mL of deionized water, then add 4.7 g of HEMA monomer. After stirring the mixture magnetically for 4 h in the dark at 4 °C, add 1 mL of MXene nanosheet aqueous suspension with a concentration of 2.5 mg / mL (mass fraction of 0.5‰) and stir until uniformly dispersed. Further add the photoinitiator 2,2-diethoxyacetophenone (1.0% of the total mass of mHACC-Azo-GCV and HEMA), and stir in the dark for 30 min until the system is homogeneous. Inject the resulting mixture into a mold consisting of two glass plates and a silicone gasket, and irradiate it under ultraviolet light for 30 min to obtain the crude hydrogel product. After purification by soaking in deionized water, p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material is obtained.

[0091] The p(HEMA-co-mHACC-Azo-GCV) / MXene hydrogel material prepared in Example 5 was characterized by FT-IR. The obtained infrared spectrum curve was similar to that of Example 1, indicating that the hydrogel material was successfully synthesized by the preparation method of Example 5.

[0092] The above descriptions are merely some embodiments of the present invention. Those skilled in the art can make various modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a photothermal controlled-release drug-eluting hydrogel corneal contact lens material, characterized in that, Includes the following steps: S1. Dissolve 4,4'-azobis(4-cyanopentanoic acid) in a first acidic system. Add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to the first acidic system with a pH of 3.0~6.

5. Stir at 0~10℃ in the dark for 20~40 min. Then add an aqueous solution of hydroxypropyltrimethylammonium chloride chitosan, react, purify, and obtain the first product. S2. Dissolve the first product in the second acidic system. Add 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide to the second acidic system with a pH of 3.0~6.

5. Then stir in the dark at 0~8℃ for 20~40 min. Add an aqueous solution of ganciclovir, react, purify, and obtain the second product. S3. Dissolve the second product in water, then add methacrylic anhydride to obtain the reaction system. The reaction system is carried out under the conditions of pH 6.5-8.5, 0-8℃, and protection from light. After purification, the third product is obtained. S4. Dissolve the third product in water, add hydroxyethyl methacrylate and MXene nanosheets to the water in sequence, then add a photoinitiator to obtain a mixture. Irradiate the mixture under ultraviolet light for 10-30 min to obtain the final product.

2. The preparation method according to claim 1, characterized in that, The photoinitiator is selected from at least one of 2,2-diethoxyacetophenone, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylphenylacetone, and 2-methyl-1-[4-(methylthio)phenyl]-2-morpholino-1-propanone; the first acidic system and the second acidic system are acetic acid.

3. The preparation method according to claim 1, characterized in that, In step S2, the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and the carboxyl group in the first product is (1~10):(1~10):1; the molar ratio of the carboxyl group in the first product to ganciclovir is 1:1 to 1:

4.

4. The preparation method according to claim 1, characterized in that, In step S1, the molar ratio of the carboxyl groups in 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N-hydroxysuccinimide, and 4,4'-azobis(4-cyanopentanoic acid) is (1~10):(1~10):1; the molar ratio of the amino group in hydroxypropyltrimethylammonium chloride chitosan to 4,4'-azobis(4-cyanopentanoic acid) is 1:0.1 to 1:

10.

5. The preparation method according to claim 1, characterized in that, In step S3, the molar ratio of the second product to methacrylic anhydride is 1:1 to 1:

9.

6. The preparation method according to claim 1, characterized in that, In step S4, the amount of the third product is 1% to 6% of the total mass of the third product and hydroxyethyl methacrylate; the amount of water is 30% to 50% of the total mass of the third product, hydroxyethyl methacrylate, and water; the amount of Xene nanosheets is 0.1 wt‰ to 0.5 wt‰ of the total mass of the third product and hydroxyethyl methacrylate; and the amount of photoinitiator is 0.1% to 1.0% of the total mass of the third product and hydroxyethyl methacrylate.

7. The preparation method according to claim 1, characterized in that, The MXene nanosheets were prepared by the following steps: Lithium fluoride was mixed with hydrochloric acid solution, and Ti3AlC2 was added. The mixture was then stirred to complete the etching of the Al layer and obtain a suspension. The suspension was centrifuged and the precipitate was washed until the pH of the supernatant was 6.5-7.

5. Then, the precipitate was dispersed in deionized water, sonicated under an inert atmosphere, centrifuged, and the supernatant was collected to obtain a suspension of MXene nanosheets. The suspension was then freeze-dried to obtain the final product.

8. The preparation method according to claim 1, characterized in that, In steps S1, S2 and S3, the reaction time is 4 to 48 hours; the purification method is to obtain the retention solution by dialysis; the molecular weight cutoff of the dialysis bag used for dialysis is 8000 Da.

9. A photothermal controlled-release hydrogel corneal contact lens material prepared by the preparation method according to any one of claims 1-8.

10. The use of the photothermal controlled-release hydrogel corneal contact lens material according to claim 9 in the preparation of materials for treating ophthalmic diseases.

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