CN114939192B

CN114939192B - Hydrogel for scleral nail as well as preparation method and application thereof

Info

Publication number: CN114939192B
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: 2023-05-12
Anticipated expiration: 2042-07-01
Also published as: CN114939192A

Abstract

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

Description

Hydrogel for scleral nail as well as preparation method and application thereof

Technical Field

The invention belongs to the field of medical polymer materials, and particularly relates to hydrogel for scleral nails, 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 caused by abnormal blood flow. Worldwide, age-related macular degeneration (AMD) and Diabetic Retinopathy (DR) are the most common retinal diseases, approximately 207 ten thousand and 769 ten thousand patients, respectively. Pathologic angiogenesis is the primary cause of retinopathy, which can lead to overgrowth of the neovasculature. These immature new blood vessels may leak out, leading to vitreous hemorrhage, fibrosis, tractional retinal detachment, and ultimately retinal damage. Thus, minimizing aberrant angiogenesis is important for the treatment of RVD.

Clinically, one widely recommended method is to deliver anti-vascular endothelial growth factor (anti-VEGF drug) or steroid (dexamethasone, etc.) to intravitreal injection. This delivery method can locate the drug in the posterior segment of the ocular tissue, as compared to eye drops. Recent studies have demonstrated that anti-VEGF drugs (such as bevacizumab and albesizumab) can improve vision and reduce side effects. However, the anti-VEGF drug has a short half-life in the vitreous and needs to be injected once a month, but repeated injections cause physical pain to the patient and are more likely to induce a strong destructive intraocular inflammation, i.e., aseptic intraocular inflammation.

Over the past several decades, various engineering strategies (such as 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 release locally at the damaged eye tissue and their low side effects. Implantable intraocular drug delivery devices such as Retisert, iluvien, surodex, ozurdex, portDelivery System (PDS) are undergoing FDA review or approval, which limits their use to some extent due to the complex structural design and the need for specific manufacturing techniques. AungThan et al reported a detachable microneedle eye mask loaded with an anti-VEGF drug and an anti-inflammatory drug (diclofenac), and animal model experiments demonstrated that the eye mask could reduce the neovascular area by about 90%, but the detachable microneedle on the eye mask easily caused corneal damage, causing physical and psychological distress to the patient.

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

Disclosure of Invention

Aiming at the problems and the defects existing in the prior art, the invention aims at providing a preparation method of hydrogel for scleral nails and the hydrogel for scleral nails prepared by the preparation method.

In order to achieve the aim of the invention, the technical scheme adopted by the invention is as follows:

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

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

(2) Adding a pore-forming agent into the chitosan-polysaccharide solution prepared in the step (1), uniformly mixing to obtain a mixed solution, injecting the mixed solution into a mold, and performing freezing and aging treatment to obtain hydrogel;

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

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

(5) Adding the medicine 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 scaffold prepared in the step (4) by adopting a spraying or dipping method, and then carrying out illumination or radiation treatment and freeze drying to obtain the hydrogel for scleral nails.

According to the above method for preparing a hydrogel for scleral spike, preferably, the molecular weight of the chitosan in the step (1) is 300000 ～ 1000000, and the chitosan concentration in the chitosan solution is 3wt%.

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

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

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

According to the above method for preparing a hydrogel for scleral spike, 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 above method for preparing a hydrogel for scleral spike, preferably, the weight of the porogen in the step (2) is 0 to 50% of the weight of the chitosan-polysaccharide solution.

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

According to the above method for preparing a hydrogel for scleral spike, preferably, the regeneration time in the step (3) is 48 to 72 hours.

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

According to the above method for preparing hydrogel for scleral spike, preferably, the method for removing polysaccharide in the porous sponge scaffold in step (4) is a high temperature steaming method.

According to the preparation method of the hydrogel for scleral spike, preferably, the high temperature steaming method is carried out at a temperature of 90-100 ℃ for 6-12 hours.

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

According to the above method for preparing a hydrogel for scleral spike, more preferably, the drug is dexamethasone.

According to the above method for preparing a hydrogel for scleral spike, preferably, the molecular weight of polyethylene glycol diacrylate in the step (5) is 200-1000.

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

According to the above method for preparing a hydrogel for scleral spike, the photoinitiator in the step (5) is preferably at least one of I2959, omnirad TPO-L, omnirad 184, omnirad 184D, darocur MBF, omniradDETX, omnirad 369, omnirad ITX, and IGM 907.

According to the preparation method of the hydrogel for scleral spike, more preferably, the photoinitiator is I2959.

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

The invention also provides hydrogel for scleral nails prepared by the preparation method.

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

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

(1) The porous chitosan scaffold is soaked in an aqueous solution of polyethylene glycol diacrylate containing a drug and a photoinitiator, and ultraviolet crosslinking reaction is carried out to obtain the scleral peg hydrogel, a pore-forming agent is introduced into the system to form a pore channel structure, after water-soluble polysaccharide is continuously introduced, the pore-forming agent and the water-soluble polysaccharide act together to form more pore channel structures of the hydrogel, and part of pore structures are converted into a communication pore structure from a closed pore structure, the pore structures are compact, the pores are communicated with each other, the porosity is high, the drug release rate of the drug can be effectively reduced, the half life of the drug in a vitreous body can be prolonged, the inflammatory concentration and the bacterial growth of wound surfaces can be effectively inhibited, the healing of scleral incisions can be promoted, and a good environment is provided for the healing of the scleral incisions, so that the porous chitosan hydrogel has wide market demands and popularization and application values.

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

(3) The preparation method adopts the operation steps of freezing, ageing treatment, regeneration, direct freeze-drying, and finally high-temperature steaming to remove soluble polysaccharide, so that the chitosan scaffold is prepared by freeze-drying again after a communicating pore structure is formed in the hydrogel, and the operation steps can avoid the change of a columnar structure in the preparation process, so that the columnar porous chitosan scaffold is obtained.

Drawings

FIG. 1 is a scanning electron microscope image of a hydrogel for scleral spikes of varying agarose and porogen content;

FIG. 2 porosity of hydrogels for scleral nails with different agarose and porogen levels;

FIG. 3 cell viability of hydrogels for scleral nails with different agarose and porogen levels;

FIG. 4 fluorescent staining of live-dead cells of hydrogel (A30-30) for scleral spike;

FIG. 5 compressive strength of hydrogels for scleral nails with different agarose and porogen levels;

FIG. 6 bacteriostatic properties of hydrogels for scleral nails with different agarose and porogen levels;

FIG. 7 illustrates the water-absorbing deformation expansion of hydrogel (A30-30) for scleral spike;

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

FIG. 9 inhibition of neovasculature by hydrogel (A30-30) for scleral spike;

FIG. 10 drug release profile of hydrogel (A30-30) for scleral spike.

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 scleral nails, experiments of examples 1 to 7 are carried out, and the hydrogel for seven scleral nails is prepared by using different agarose contents and different pore-forming agent contents, and comprises the following specific steps:

(1) Preparing alkali urea solution with lithium hydroxide concentration of 4.5wt%, potassium hydroxide concentration of 7wt% and urea concentration of 8wt%, dissolving chitosan and agarose into the alkali urea solution to obtain chitosan solution and polysaccharide solution, wherein the chitosan concentration in the chitosan solution is 3wt% and the polysaccharide concentration in the polysaccharide solution is 3wt%, and uniformly mixing the chitosan solution and the polysaccharide solution according to the weight ratio (see table 1 in particular) to obtain chitosan-polysaccharide solution;

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

(3) Placing the hydrogel prepared in the step (2) into 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 bracket prepared in the step (3) in water at 100 ℃ for 8 hours, removing polysaccharide in the porous sponge bracket, and freeze-drying at-20 ℃ to obtain a porous chitosan bracket;

(5) Dissolving dexamethasone in ethanol to obtain dexamethasone solution with concentration of 20mg/mL, adding 1mL dexamethasone solution into aqueous solution containing polyethylene glycol diacrylate (molecular weight 200) and photoinitiator I2959, mixing to obtain mixed solution, and concentrating polyethylene glycol diacrylate and photoinitiatorThe degrees were 20wt% and 0.1wt%, respectively; loading the mixed solution on the porous chitosan bracket prepared in the step (4) by adopting a spraying or dipping method, wherein the wavelength is 365nm, and the intensity is 205mW/cm ² Is irradiated by ultraviolet light for 10min, and then is frozen and dried at the temperature of minus 20 ℃ to obtain the hydrogel for scleral spike.

The hydrogels for scleral nails prepared in examples 1-7 above using different agarose levels and porogen levels were designated Ax-y (x is agarose level, y is porogen level), see in particular table 1.

TABLE 1

Performance testing

The Ax-y prepared in examples 1 to 7 of the present invention were subjected to the following characterization and performance tests:

1. scanning electron microscope analysis

The scleral nails prepared in examples 1 to 7 were analyzed by a scanning electron microscope using hydrogel Ax-y, and the results are shown in FIG. 1.

As can be seen from FIG. 1, all the hydrogels for scleral nails show rich pore structures, and when only the pore-forming agent anhydrous sodium sulfate is introduced into the system (A0-30), the pore structures of the hydrogels for scleral nails are mostly closed pore structures. When agarose is introduced into the system, the partial pore structure of the hydrogel for scleral nail starts to change from a closed pore structure to a communicating pore structure, and as can be seen from comparison of examples 1 to 4, the agarose content increases, but when the agarose content is 50wt%, the hydrogel for scleral nail becomes relatively soft, and the partial pore structure starts to collapse. When the agarose content is 30wt%, the hydrogel pore structure of the scleral spike is compact, and pores are communicated, so that the mechanical property of the scleral spike is improved, and the drug release efficiency of the scleral spike is delayed. When agarose content (30 wt%) in the system was fixed, it was found from comparison of example 3 and examples 5 to 7 that, as the anhydrous sodium sulfate content in the system was increased, the hydrogel pore structure for scleral spike became larger and the communication pore structure was decreased, because anhydrous sodium sulfate was favorable to promote gelation of the solution, and the higher the anhydrous sodium sulfate content was, the higher the degree of gelation was, the crosslinking between agarose and chitosan was promoted, and dissolution of agarose was reduced.

2. Determination of porosity

The porosity of the hydrogels Ax-y for scleral nails 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 30wt% of the weight of the chitosan-polysaccharide solution, the porosity of the hydrogel for scleral spike increases with the increase of agarose content. When the agarose content in the fixing system is 30wt%, the porosity of the hydrogel for scleral nails is increased and then reduced along with the increase of the anhydrous sodium sulfate content, because when the anhydrous sodium sulfate content is too high, the crosslinking of agarose and chitosan is promoted, the dissolution of agarose is reduced, and the porosity of the agarose is further reduced.

3. Cytotoxicity assays

Cytotoxicity of the hydrogels Ax-y for scleral nails 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 fixation system was 30wt% (examples 1 to 4), the cell viability of the scleral nail hydrogel was 94.+ -. 4.5%, 87.5.+ -. 3.6%, 81.5.+ -. 3% and 82.+ -. 3% on day 1, respectively, and when the content of agarose in the fixation system was 30wt% (examples 3, examples 5 to 7), the cell viability of the scleral nail hydrogel was 98.5.+ -. 3.6%, 92.+ -. 3.8%, 81.5.+ -. 3% and 65.5.+ -. 1.6%, respectively, on day 1, respectively, whereby it was found that it was possible to cause slight damage to cells regardless of the increase in the amount of anhydrous sodium sulfate or the increase in the amount of agarose, which was unfavorable for cell proliferation. When the content of anhydrous sodium sulfate in the fixation system was 30wt%, the cell viability of the hydrogel for scleral spike 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 fixation system was 30wt%, the cell viability of the hydrogels for scleral nails was 106.5.+ -. 7%, 94.+ -. 3.8%, 87.5.+ -. 4.5% and 57.+ -. 3.2% at 3 days, 136.+ -. 1.8%, 109.+ -. 2.4%, 108.+ -. 1.8% and 52.+ -. 0.9% at 7 days, respectively. Therefore, other components of the hydrogel except the A30-50 show better cell compatibility, and the cell proliferation can be promoted along with the extension of time, and for the A30-50 group, the cross-linking of agarose and chitosan is promoted when the anhydrous sodium sulfate content is too high, so that the dissolution of the agarose is reduced, and the cytotoxicity is further increased.

4. Fluorescent staining of live-dead cells

The scleral spike prepared in example 3 was stained with hydrogel A30-30 by fluorescence of live-dead cells at 0h,24h and 48h, respectively, and the results are shown in FIG. 4.

As can be seen from fig. 4, with the extension of the culture time, the cells gradually proliferate, and the hydrogel (a 30-30) for scleral nails has better cell compatibility, and can promote the proliferation of cells, thereby being beneficial to the healing of the surgical wound surface.

5. Compressive Strength test

The compressive strength of the hydrogels Ax-y for scleral nails 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 scleral spike is gradually reduced with the increase of the anhydrous sodium sulfate or agarose content, because the porosity and softness of the chitosan scaffold can be increased and the mechanical strength thereof can be reduced no matter the anhydrous sodium sulfate or agarose is introduced.

6. Antibacterial property test

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

As can be seen from fig. 6, each group of samples can inhibit the growth of escherichia coli and staphylococcus aureus, and as is evident from the digital photograph of the agar plate, the escherichia coli and staphylococcus aureus of the control group form compact colonies on the agar surface, while for each group of the scleral nail hydrogel, substantially no colony is formed, and as is evident from the corresponding fluorescent staining of live-dead bacteria, the control group (original bacterial liquid) shows bright green (representing live bacteria), and each group of the scleral nail hydrogel shows bright red (representing dead bacteria), and substantially no green, and the result shows that the scleral nail hydrogel has excellent antibacterial performance, can prevent bacterial growth at the incision site of surgery, and further reduce the probability of postoperative ocular bacterial infection.

7. Water absorption deformation expansion condition test

The scleral spike prepared in example 3 was tested for swelling by water absorption deformation using hydrogels A30-30 and the results are shown in FIG. 7.

As can be seen from fig. 7, the compressed hydrogel (a 30-30) for scleral spike can absorb water within 10s to rapidly expand its volume, which is beneficial to rapidly seal the eye surgical incision, prevent bacterial infection, avoid surgical suturing, and reduce the surgical workload.

8. Inhibition of inflammatory factors

The scleral spike prepared in example 3 was tested for inhibition of inflammatory factors by hydrogels A30-30 and the results are shown in FIG. 8.

As can be seen from fig. 8, hypoxia causes damage to the blood retinal barrier, which results in reduced expression of the related protein ZO1 (second column), and when hydrogel for scleral spike (third column) and dexamethasone drug (fourth column) are added, the expression of ZO1 protein is promoted, and the damage to the blood retinal barrier caused by hypoxia can be improved, so that the blood retinal barrier is stabilized. Meanwhile, the hypoxia can cause the rise of the inflammation level, promote the expression of related protein IL18, further strengthen the damage of the blood retina barrier, and when hydrogel (the third column) and dexamethasone medicine (the fourth column) for scleral spike are added, the expression of IL18 protein can be inhibited, and the anti-inflammatory effect is better, so that the blood retina barrier is protected. The hydrogel for scleral spike and dexamethasone drug group have better anti-inflammatory effect and blood retinal barrier protection effect, and the result shows that the hydrogel for scleral spike can achieve the same anti-inflammatory effect and blood retinal barrier protection effect as the pure injection of dexamethasone.

9. Inhibition of neovascular growth

The scleral spike prepared in example 3 was tested for inhibition of neovasculature by hydrogels A30-30 and the results are shown in FIG. 9.

Fig. 9 is a fluorescent staining of rhesus monkey chorioretinal endothelial cell tube forming experiments under hypoxic conditions that promote cell formation of a luminal-like structure, and it is evident from the figure that under hypoxic conditions, cells form more luminal-like structures, while the integrity and number of luminal-like structures are significantly inhibited when scleral nails and dexamethasone drug made with hydrogels of the present application are added. The increase of cell lumen represents the increase of new blood vessel, and the new blood vessel formation can be obviously inhibited when the hydrogel for scleral nail and dexamethasone medicine are added, and the result shows that the prepared hydrogel for scleral nail can achieve the same effect of inhibiting the blood vessel formation as the pure injection of dexamethasone.

10. Drug sustained release profile

The scleral spike prepared in example 3 was tested for drug release in hydrogels A30-30 and drug release curves were prepared and the results are shown in FIG. 10.

As can be seen from fig. 10, the release of dexamethasone from the hydrogel for scleral spike (a 30-30) shows a relatively stable release rate, and the total release amount is only 39.1±2.4% at 33 days, which indicates that the hydrogel for scleral spike with drug can maintain a longer drug release period, thereby satisfying the effect of continuous treatment of ocular diseases and avoiding intraocular infection, economic pressure and pain of patients caused by repeated drug injection in a short period.

The embodiments described above are specific embodiments of the present invention, but the embodiments of the present invention are not limited to the embodiments described above, and any other combinations, changes, modifications, substitutions, and simplifications that do not exceed the design concept of the present invention fall within the scope of the present invention.

Claims

1. A method for preparing hydrogel for scleral nails, comprising the following steps:

(2) Adding a pore-forming agent into the chitosan-polysaccharide solution prepared in the step (1), uniformly mixing to obtain a mixed solution, injecting the mixed solution into a mold, and performing freezing and aging treatment to obtain hydrogel; the pore-forming agent is one or more of sodium sulfate decahydrate, anhydrous sodium sulfate and anhydrous magnesium sulfate;

(4) Soaking the porous sponge scaffold prepared in the step (3) in water, removing polysaccharide in the porous sponge scaffold, and then freeze-drying to obtain the porous chitosan scaffold;

2. The method of claim 1, wherein the chitosan in step (1) has a molecular weight of 300000 ～ 1000000 and the chitosan in the chitosan solution has a concentration of 3-wt%.

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

4. The method of preparing a hydrogel for scleral spike as claimed in claim 1, wherein the ratio in step (1) is a weight ratio of chitosan solution: polysaccharide solution = 90-50: 10 to 50 percent.

5. The method for preparing hydrogel for scleral spike as claimed in 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 of claim 1, wherein the weight of the porogen in step (2) is 10-50% of the weight of the chitosan-polysaccharide solution.

7. The method for preparing a hydrogel for scleral spike according to any one of claims 1 to 6, wherein the drug is at least one of dexamethasone, ranibizumab, bevacizumab, tobramycin, levofloxacin, ofloxacin, gatifloxacin, fluorometholone, loteprednol, pranoprofen, diclofenac sodium, bromfenac sodium, ibuprofen.

8. A hydrogel for scleral spike prepared by the method of any one of claims 1 to 7.

9. Use of the hydrogel of claim 8 in scleral spur.