CN114939192A

CN114939192A - Hydrogel for scleral nail and preparation method and application thereof

Info

Publication number: CN114939192A
Application number: CN202210773420.8A
Authority: CN
Inventors: 万光明; 范夏莲; 薛瑢; 杨倩; 梁申芝; 王炯; 董一; 钱诚; 董怡辰
Original assignee: First Affiliated Hospital of Zhengzhou University
Current assignee: First Affiliated Hospital of Zhengzhou University
Priority date: 2022-07-01
Filing date: 2022-07-01
Publication date: 2022-08-26
Anticipated expiration: 2042-07-01
Also published as: CN114939192B

Abstract

The invention discloses a preparation method of hydrogel for scleral pins, which comprises the following steps: firstly, preparing a porous chitosan bracket by using a pore-foaming agent and a polysaccharide dissolving strategy; loading the mixed solution containing the drug, the polyethylene glycol diacrylate and the photoinitiator on the porous chitosan bracket by adopting a spraying or dipping method, then carrying out illumination or radiation treatment, and carrying out freeze drying to obtain the hydrogel for the scleral pin. The hydrogel for the scleral pin is prepared by the preparation method, and on one hand, the hydrogel for the scleral pin can effectively reduce the drug release rate of the drug, prolong the half-life period of the drug in vitreous body, effectively inhibit the growth of inflammatory medium and vascular endothelial growth factor, and on the other hand, can absorb the expansion of body fluid, block scleral incision, reduce the operation steps of surgical suture and prevent infection.

Description

Hydrogel for scleral nail and preparation method and application thereof

Technical Field

The invention belongs to the field of medical polymer materials, and particularly relates to hydrogel for scleral pins, and a preparation method and application thereof.

Background

Retinal Vascular Disease (RVD) is a major cause of vision impairment and blindness. It is usually caused by neovascularization or retinal damage due to abnormal blood flow. Globally, age-related macular degeneration (AMD) and Diabetic Retinopathy (DR) are the most common retinal diseases, with about 207 and 769 million patients, respectively. Pathological angiogenesis is the major cause of retinopathy, which can lead to overgrowth of neovasculature. These immature blood vessels may exude fluid, resulting in vitreous hemorrhage, fibrosis, tractional retinal detachment, and ultimately retinal damage. Therefore, minimizing abnormal angiogenesis is important for the treatment of RVD.

Clinically, one widely recommended method is to deliver anti-vascular endothelial growth factor (anti-VEGF drugs) or steroids (dexamethasone, etc.) to intravitreal injections. This method of delivery allows the drug to be localized to the posterior segment of the ocular tissue, as opposed to eye drops. Recent studies have demonstrated that anti-VEGF drugs (such as ranibizumab, bevacizumab and aflibercept) can improve vision and reduce side effects. However, the anti-VEGF drugs have a short half-life in the vitreous, requiring monthly injections, but repetitive injections can cause physical distress to the patient and are more likely to induce a highly destructive endophthalmitis, aseptic endophthalmitis.

Over the past several decades, various engineering strategies (e.g., nano/micro drug carriers, injectable hydrogels, and drug-loaded implants) have been demonstrated to extend the release time of drugs in the vitreous, where drug-loaded implants have received much attention due to their ability to be released locally at damaged ocular tissues and their low side effects. Implantable intraocular drug delivery devices such as reissert, ilivien, suredex, azurdex, PortDelivery System (PDS) are under FDA scrutiny or approval, which limits their application to some extent due to their complex structural design and the need for specific manufacturing techniques. AungThan et al reported a detachable microneedle patch loaded with anti-VEGF drug and anti-inflammatory drug (diclofenac), and animal model experiments confirmed that the patch can reduce the neovascular neoarea by about 90%, but the detachable microneedle on the patch easily causes corneal injury, which brings physical and psychological pain to patients.

In view of the defects and limitations of the existing Retinal Vascular Disease (RVD) treatment method, a new medicine carrying material prepared by a new method needs to be researched, so that the medicine carrying material has a longer half-life period and higher water absorption expansion, can be locally released at the position of a scleral incision where eye tissues are damaged and can be used for plugging an operation incision by self expansion, and the purposes of treating intraocular diseases, reducing the complexity of the operation and reducing the infection probability are achieved.

Disclosure of Invention

In view of the problems and disadvantages of the prior art, an object of the present invention is to provide a method for preparing a hydrogel for a scleral pin and a hydrogel for a scleral pin prepared thereby.

In order to realize the purpose of the invention, the technical scheme adopted by the invention is as follows:

the invention firstly provides a preparation method of hydrogel for scleral pins, which comprises the following steps:

(1) respectively dissolving chitosan and polysaccharide in an alkaline urea system to obtain a chitosan solution and a polysaccharide solution, and uniformly mixing the chitosan solution and the polysaccharide solution in proportion to obtain a chitosan-polysaccharide solution;

(2) adding a pore-foaming agent into the chitosan-polysaccharide solution prepared in the step (1), uniformly mixing to obtain a mixed solution, injecting the mixed solution into a mould, and freezing and aging to obtain hydrogel;

(3) placing the hydrogel prepared in the step (2) in water for regeneration, removing an alkali urea solvent, and then freezing and shaping to obtain a porous sponge support;

(4) soaking the porous sponge support prepared in the step (3) in water, steaming at high temperature, removing polysaccharide in the porous sponge support, and then freeze-drying to obtain a porous chitosan support;

(5) adding the medicinal solution into an aqueous solution containing polyethylene glycol diacrylate and a photoinitiator, and uniformly mixing to obtain a mixed solution; and (3) loading the mixed solution on the porous chitosan stent prepared in the step (4) by adopting a spraying or dipping method, then carrying out illumination or radiation treatment, and carrying out freeze drying to obtain the hydrogel for the scleral pin.

According to the preparation method of the hydrogel for the scleral peg, preferably, the chitosan in step (1) has a molecular weight of 300000-1000000, and the chitosan solution has a chitosan concentration of 3 wt%.

According to the above method for preparing a hydrogel for a scleral peg, preferably, the polysaccharide in step (1) is a water-soluble polysaccharide, and the concentration of the polysaccharide in the polysaccharide solution is 3 wt%.

According to the above method for preparing the hydrogel for a scleral peg, preferably, the water-soluble polysaccharide is at least one of agarose, trehalose, dextran, sodium hyaluronate, and konjac glucomannan.

According to the preparation method of the hydrogel for the scleral pin, preferably, the ratio in the step (1) is a weight ratio, and the weight ratio is chitosan solution: polysaccharide solution is 100-50: 0 to 50.

According to the preparation method of the hydrogel for the scleral nail, preferably, the pore-forming agent in the step (2) is one or more of sodium sulfate decahydrate, anhydrous sodium sulfate and anhydrous magnesium sulfate.

According to the preparation method of the hydrogel for the scleral peg, preferably, the weight of the pore-forming agent in the step (2) is 0-50% of the weight of the chitosan-polysaccharide solution.

According to the preparation method of the hydrogel for the scleral pin, the freezing temperature in the step (2) is preferably-20 ℃ to-80 ℃, and the aging time is preferably 24h to 48 h.

According to the preparation method of the hydrogel for the scleral peg, the regeneration time in the step (3) is preferably 48 to 72 hours.

According to the preparation method of the hydrogel for the scleral pin, the temperature for freezing and shaping in the step (3) is preferably-40 ℃ to-60 ℃, and the freezing time is preferably 48h to 72 h.

According to the preparation method of the hydrogel for the scleral peg, preferably, the method for removing the polysaccharide from the porous sponge scaffold in the step (4) is a high-temperature cooking method.

According to the preparation method of the hydrogel for the scleral peg, the high-temperature cooking method is preferably performed at the temperature of 90-100 ℃ for 6-12 hours.

According to the preparation method of the hydrogel for the scleral pin, preferably, the drug solution in the step (5) is prepared by dissolving the drug in ethanol, and the concentration of the drug in the drug solution is 5-30 mg/mL.

According to the preparation method of the hydrogel for the scleral peg, preferably, the drug is at least one of dexamethasone, ranibizumab, bevacizumab, tobramycin, levofloxacin, ofloxacin, gatifloxacin, fluorometholone, loteprednol etabonate, pranoprofen, diclofenac sodium, bromfenac sodium and ibuprofen.

According to the preparation method of the hydrogel for the scleral nail, the drug is dexamethasone.

According to the preparation method of the hydrogel for the scleral peg, in the step (5), the molecular weight of the polyethylene glycol diacrylate is preferably 200 to 1000.

According to the above preparation method of hydrogel for scleral screw, preferably, the concentration of the polyethylene glycol diacrylate in the mixed solution of the step (5) is 20wt% to 50 wt%, and the concentration of the photoinitiator in the mixed solution is 0.01 wt% to 0.5 wt%.

According to the above method for preparing a hydrogel for a scleral nail, preferably, the photoinitiator in step (5) is at least one of I2959, Omnirad TPO-L, Omnirad 184, Omnirad 184D, Darocur MBF, Omnirad detx, Omnirad 369, Omnirad ITX, IGM 907.

According to the preparation method of the hydrogel for the scleral pin, the photoinitiator is I2959.

According to the above method for preparing a hydrogel for a scleral pin, preferably, the irradiation of the light in the step (5) is ultraviolet light having a wavelength of 365nm and an intensity of 205mW/cm ² The irradiation time is 10 min.

The invention also provides the hydrogel for the scleral pin, which is prepared by the preparation method.

The invention also provides application of the hydrogel in scleral pins.

Compared with the prior art, the invention has the following positive beneficial effects:

(1) the invention is characterized in that a porous chitosan bracket is soaked in a water solution containing polyethylene glycol diacrylate containing medicine and photoinitiator, hydrogel for scleral nail is obtained through ultraviolet light crosslinking reaction, pore-forming agent is introduced into the system to form a pore structure, after water-soluble polysaccharide is continuously introduced, the pore-forming agent and the water-soluble polysaccharide act together to form more pore structures on the hydrogel, and part of the pore structures are converted from closed pore structures to communicated pore structures, the pore structures are compact and communicated with each other, the porosity is high, the medicine release rate of the medicine can be effectively reduced, the half-life period of the medicine in vitreous body can be prolonged, the inflammation concentration and the wound surface bacterial growth can be effectively inhibited, the scleral incision healing can be promoted, a good environment can be provided for the scleral incision healing, and the invention has wide market demand and popularization and application value.

(2) The hydrogel for the scleral nail prepared by the invention has good water-absorbing expansion effect, and the prepared scleral nail can absorb body fluid to expand when inserted into a scleral incision to block the scleral incision, so that the scleral nail can bear aqueous humor pressure, is not easy to fall off from the scleral incision, and can provide a good recovery environment after an internal eye operation.

(3) The chitosan scaffold is prepared by adopting the operation steps of freezing, aging, regenerating, then directly freeze-drying, and finally cooking at high temperature to remove soluble polysaccharide, so that a communicating pore structure is formed in the hydrogel and then freeze-drying is carried out again.

Drawings

FIG. 1 scanning electron micrographs of hydrogels for scleral pins of different agarose and porogen contents;

FIG. 2 porosity of hydrogel for scleral pins of different agarose and porogen contents;

FIG. 3 cell viability of sclerosant pins with hydrogels of different agarose and porogen content;

FIG. 4 fluorescence staining of the scleral pins with live-dead cells of hydrogel (A30-30);

FIG. 5 compressive strength of hydrogels for scleral pins of different agarose and porogen content;

FIG. 6 the bacteriostatic properties of the hydrogel for scleral pins with different agarose and porogen contents;

FIG. 7 the scleral pin was inflated with the water-absorbing deformation of hydrogel (A30-30);

FIG. 8 inhibition of inflammatory factors by hydrogel for scleral pins (A30-30);

FIG. 9 inhibition of neovascularization by hydrogel (A30-30) in scleral nail;

FIG. 10 drug release profile of the scleral pin with hydrogel (A30-30).

Detailed Description

The present invention is further illustrated by the following specific examples, which are not intended to limit the scope of the invention.

Examples 1 to 7

According to the preparation method of the hydrogel for the scleral pin, disclosed by the invention, experiments of examples 1-7 are carried out, seven types of hydrogels for the scleral pin are prepared by using different agarose contents and different pore-forming agent contents, and the concrete steps are as follows:

(1) taking lithium hydroxide, potassium hydroxide, urea and water, preparing an alkali urea solution with the concentration of 4.5 wt% of lithium hydroxide, the concentration of 7 wt% of potassium hydroxide and the concentration of 8 wt% of urea, respectively dissolving chitosan and agarose in the alkali urea solution to obtain a chitosan solution and a polysaccharide solution, wherein the concentration of chitosan in the chitosan solution is 3 wt% and the concentration of polysaccharide in the polysaccharide solution is 3 wt%, and uniformly mixing the chitosan solution and the polysaccharide solution according to the weight ratio (specifically referring to table 1) to obtain a chitosan-polysaccharide solution;

(2) adding pore-foaming agent anhydrous sodium sulfate into the chitosan-polysaccharide solution prepared in the step (1), wherein the weight of the pore-foaming agent is 0-50 wt% of that of the chitosan-polysaccharide solution (see table 1 specifically), uniformly mixing to obtain a mixed solution, injecting the mixed solution into a mold, and performing freezing and aging treatment at-20 ℃ for 48 hours to obtain hydrogel;

(3) placing the hydrogel prepared in the step (2) in water for regeneration for 48 hours, changing water every three hours, and then freezing and shaping at the temperature of minus 20 ℃ to obtain a porous sponge bracket;

(4) soaking the porous sponge scaffold prepared in the step (3) in water at 100 ℃ for 8h, removing polysaccharide in the porous sponge scaffold, and freeze-drying at-20 ℃ to obtain a porous chitosan scaffold;

(5) dissolving dexamethasone in ethanol to prepare a dexamethasone solution with the concentration of 20mg/mL, adding 1mL of the dexamethasone solution into an aqueous solution containing polyethylene glycol diacrylate (molecular weight 200) and a photoinitiator I2959, and uniformly mixing to obtain a mixed solution, wherein the concentrations of the polyethylene glycol diacrylate and the photoinitiator in the mixed solution are respectively 20wt% and 0.1 wt%; loading the mixed solution on the porous chitosan scaffold prepared in the step (4) by adopting a spraying or dipping method, wherein the wavelength of the mixed solution is 365nm, and the intensity of the mixed solution is 205mW/cm ² Irradiating with ultraviolet light for 10min, and freeze drying at-20 deg.C to obtain hydrogel for sclera nail.

The hydrogel for scleral pins prepared in examples 1-7 using different agarose contents and porogen contents was named Ax-y (x is the agarose content and y is the porogen content), see table 1 for details.

TABLE 1

Performance testing

Ax-y prepared in the embodiments 1-7 of the invention is subjected to the following characterization and performance test:

1. analysis by scanning Electron microscope

Scanning electron microscope analysis was performed on the scleral pins prepared in examples 1 to 7 using hydrogel Ax-y, and the results are shown in fig. 1.

As can be seen from FIG. 1, the hydrogel for the scleral pin all showed a rich pore structure, and when only anhydrous sodium sulfate as a pore-forming agent was introduced into the system (A0-30), the pore structure of the hydrogel for the scleral pin was mostly a closed pore structure. When agarose is introduced into the system, the partial pore structure of the hydrogel for the scleral pin begins to be changed from the closed pore structure to the interconnected pore structure, and as can be seen from the comparison of examples 1 to 4, the content of agarose increases, but when the content of agarose is 50 wt%, the hydrogel for the scleral pin becomes softer, and the partial pore structure begins to collapse. When the content of the agarose is 30 wt%, the pore structure of the hydrogel for the scleral pin is compact, and the pores are communicated, so that the mechanical property of the scleral pin is improved, and the drug release efficiency of the scleral pin is delayed. When the agarose content (30 wt%) in the immobilization system was high, it was found from the comparison between examples 3 and 5 to 7 that the pore structure of the hydrogel for scleral pins became large and the pore structure of the pores decreased as the content of anhydrous sodium sulfate in the system increased, because the anhydrous sodium sulfate facilitated the gelation of the solution, and the higher the content of anhydrous sodium sulfate, the higher the degree of gelation, the more the crosslinking between agarose and chitosan was promoted, and the elution of agarose was reduced.

2. Determination of porosity

The porosity of the hydrogel Ax-y for the scleral nail prepared in examples 1 to 7 was measured, and the results are shown in FIG. 2.

As can be seen from fig. 2, when the content of the porogen anhydrous sodium sulfate in the immobilization system is 30 wt% of the weight of the chitosan-polysaccharide solution, the porosity of the hydrogel for the scleral peg increases with the increase of the agarose content. When the content of agarose in the immobilization system is 30 wt%, the porosity of hydrogel for the scleral pin increases and then decreases with the increase of the content of anhydrous sodium sulfate, because when the content of anhydrous sodium sulfate is too high, the crosslinking of agarose and chitosan is promoted, the dissolution of agarose is reduced, and the porosity of agarose is further reduced.

3. Cytotoxicity assays

The cytotoxicity of the hydrogel Ax-y for the scleral pins prepared in examples 1 to 7 was measured, and the results are shown in FIG. 3.

As can be seen from FIG. 3, when the content of anhydrous sodium sulfate in the immobilization system was 30 wt% (examples 1 to 4), the cell survival rates of the hydrogel for scleral pin were 94. + -. 4.5%, 87.5. + -. 3.6%, 81.5. + -. 3% and 82. + -. 3% at 1 day, respectively, and when the content of agarose in the immobilization system was 30 wt% (examples 3, 5 to 7), the cell survival rates of the hydrogel for scleral pin were 98.5. + -. 3.6%, 92. + -. 3.8%, 81.5. + -. 3% and 65.5. + -. 1.6% at 1 day, respectively, whereby it was found that both increasing the amount of anhydrous sodium sulfate and increasing the amount of agarose may cause slight damage to the cells and adversely affect the cell proliferation. When the content of anhydrous sodium sulfate in the immobilization system was 30 wt%, the cell viability of the hydrogel for the scleral pins was 101.5. + -. 3.2%, 96.5. + -. 3.25%, 87.5. + -. 4.5% and 91. + -. 3.6% at 3 days, and 131. + -. 0.85%, 121. + -. 1%, 108. + -. 1.8% and 115. + -. 0.9% at 7 days, respectively. When the agarose content in the immobilization system was 30 wt%, the cell survival rates of the hydrogel for the scleral pins were 106.5. + -. 7%, 94. + -. 3.8%, 87.5. + -. 4.5% and 57. + -. 3.2% at 3 days, and 136. + -. 1.8%, 109. + -. 2.4%, 108. + -. 1.8% and 52. + -. 0.9% at 7 days, respectively. Therefore, the hydrogel with other components except A30-50 shows better cell compatibility and can promote the proliferation of cells with the time, and the A30-50 probably causes that when the content of the anhydrous sodium sulfate is too high, the crosslinking of agarose and chitosan is promoted, the dissolution of the agarose is reduced, and the cytotoxicity is increased.

4. Live-dead cell fluorescent staining

Live-dead cell fluorescent staining was performed on the scleral nail prepared in example 3 using hydrogel a30-30 at 0h, 24h, and 48h, respectively, and the results are shown in fig. 4.

As can be seen from FIG. 4, the cells gradually proliferate and show better cell survival rate with the prolonged culture time, and the hydrogel for scleral peg (A30-30) has better cell compatibility, can promote the proliferation of the cells and is beneficial to the healing of the surgical wound.

5. Compression strength test

The compressive strength of the hydrogel Ax-y for the scleral nail prepared in examples 1 to 7 was measured, and the results are shown in FIG. 5.

As can be seen from fig. 5, the compressive strength of the hydrogel for the scleral peg gradually decreases with the increase of the content of anhydrous sodium sulfate or agarose, because the porosity and softness of the chitosan scaffold can be increased and the mechanical strength thereof can be reduced regardless of the introduction of anhydrous sodium sulfate or agarose.

6. Test of bacteriostatic Property

The bacteriostatic properties of the hydrogel Ax-y for the scleral pins prepared in examples 1 to 7 were measured, and the results are shown in FIG. 6.

As can be seen from FIG. 6, the samples of each group can inhibit the growth of Escherichia coli and Staphylococcus aureus, and it is evident from the digital photographs of the agar plates that the Escherichia coli and the Staphylococcus aureus of the control group all form compact colonies on the agar surfaces, while almost no colonies are formed for each group of the hydrogel for the scleral peg, and it is evident from the fluorescent staining of the corresponding live-dead bacteria that the control group (original bacterial liquid) shows bright green (representing live bacteria) and each group of the hydrogel for the scleral peg basically shows bright red (representing dead bacteria) and almost no green.

7. Testing of water absorption deformation expansion condition

The scleral nail prepared in example 3 was tested for swelling with water-absorbing deformation of hydrogel a30-30, and the results are shown in fig. 7.

As can be seen from fig. 7, the hydrogel for the compressed scleral nail (A30-30) can absorb water within 10s to rapidly expand in volume, which is beneficial to rapidly blocking the surgical incision of the eye, preventing bacterial infection, avoiding surgical suture and reducing the workload of the operation.

8. Inhibiting effect on inflammatory factor

The scleral nail prepared in example 3 was tested for the inhibitory effect of hydrogel a30-30 on inflammatory factors, and the results are shown in fig. 8.

As can be seen from FIG. 8, hypoxia causes the blood retinal barrier to be damaged, and then the expression level of the related protein ZO1 is reduced (second column), and when hydrogel for scleral peg (third column) and dexamethasone drug (fourth column) are added to promote the expression of ZO1 protein, the blood retinal barrier damage caused by hypoxia can be improved, and then the blood retinal barrier is stabilized. Meanwhile, the hypoxia can cause the increase of the inflammation level, promote the expression of related protein IL18, further aggravate the damage of the blood retina barrier, and when the sclera nail hydrogel (the third column) and the dexamethasone medicament (the fourth column) are added, the expression of the IL18 protein can be inhibited, so that the anti-inflammatory effect is better, and the blood retina barrier is further protected. The results show that the hydrogel for the scleral pin can achieve the same anti-inflammatory and blood retina barrier protection effects as the single injection of dexamethasone.

9. Inhibiting effect on new blood vessel

The scleral nail prepared in example 3 was tested for the inhibition of neovascularization by hydrogel a30-30, and the results are shown in fig. 9.

Fig. 9 is a fluorescent staining of rhesus monkey chorioretinal endothelial cell tube formation experiment, which promotes the cells to form lumen-like structures under the anoxic condition, and it is obvious from the figure that the cells form more lumen-like structures under the anoxic condition, and when the scleral peg made of the hydrogel of the present application and dexamethasone drug are added, the integrity and the number of the lumen-like structures are obviously inhibited. The increase of cell lumens represents the increase of new blood vessels, the addition of the hydrogel for the scleral pin and the dexamethasone medicament can obviously inhibit the formation of the new blood vessels, and the result shows that the prepared hydrogel for the scleral pin can achieve the same effect of inhibiting the formation of the blood vessels as that of the simple injection of the dexamethasone.

10. Drug release profile

The sclera nail prepared in example 3 was tested for the sustained release of the drug in hydrogel a30-30 to prepare a drug sustained release profile, and the results are shown in fig. 10.

As can be seen from figure 10, the release of dexamethasone in the hydrogel for scleral pins (A30-30) presents a relatively smooth release rate, and the total release amount is only 39.1 +/-2.4% in 33 days, which indicates that the hydrogel for drug-loaded scleral pins can keep a longer drug release period, meets the function of continuously treating eye diseases, and avoids intraocular infection, economic pressure and patient pain caused by repeatedly injecting drugs in a short period.

The above embodiments are specific embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments, and any other combinations, changes, modifications, substitutions, and simplifications without departing from the design concept of the present invention fall within the protection scope of the present invention.

Claims

1. A preparation method of hydrogel for scleral pins is characterized by comprising the following steps:

(3) placing the hydrogel prepared in the step (2) in water for regeneration, removing the alkali urea solvent, and then freezing and shaping to obtain a porous sponge support;

(4) soaking the porous sponge support prepared in the step (3) in water to remove polysaccharide in the porous sponge support, and then freeze-drying to obtain a porous chitosan support;

2. The method for preparing hydrogel for scleral nail according to claim 1, wherein the chitosan in step (1) has a molecular weight of 300000 to 1000000 and the chitosan solution has a chitosan concentration of 3 wt%.

3. The method for preparing a hydrogel for a scleral nail according to claim 1, wherein the polysaccharide in step (1) is a water-soluble polysaccharide, and the polysaccharide solution has a polysaccharide concentration of 3 wt%.

4. The method for preparing hydrogel for scleral pins according to claim 1, wherein the ratio in step (1) is a weight ratio of chitosan solution: polysaccharide solution = 100-50: 0 to 50.

5. The method for preparing hydrogel for scleral nail according to claim 1, wherein the concentration of polyethylene glycol diacrylate in the mixed solution in the step (5) is 20wt% to 50 wt%.

6. The method for preparing hydrogel for scleral nail according to claim 1, wherein the weight of the pore-forming agent in step (2) is 0 to 50% of the weight of the chitosan-polysaccharide solution.

7. The method for preparing hydrogel for scleral nail according to claim 1, wherein the pore-forming agent in step (2) is one or more of sodium sulfate decahydrate, anhydrous sodium sulfate, and anhydrous magnesium sulfate.

8. The method for preparing the hydrogel for the sclera nail according to any one of claims 1 to 7, wherein the drug is at least one of dexamethasone, ranibizumab, bevacizumab, tobramycin, levofloxacin, ofloxacin, gatifloxacin, fluorometholone, loteprednol, pranoprofen, diclofenac sodium, bromfenac sodium and ibuprofen.

9. A hydrogel for scleral nail prepared by the method of any one of claims 1 to 8.

10. Use of the hydrogel of claim 9 in scleral pins.