Preparation method and application of vitamin E hydrogel with oxidation-reduction characteristic

Abstract

The invention discloses a preparation method and application of vitamin E hydrogel with an oxidation-reduction characteristic. The vitamin E hydrogel with the oxidation-reduction characteristic is prepared from the following components in percentage by weight: 10.0 to 30.0 percent of TPGS-SH, 0 to 10.0 percent of TPGS-SeSe-TPGS and 60 to 90.0 percent of solvent. Redox dynamic response regulation and control of the hydrogel are achieved through molecular structure design, in an oxidation environment, sulfydryl in TPGS-SH molecules is subjected to a bimolecular oxidation reaction to form a disulfide bond cross-linked dimer, a selenium-containing compound TPGS-SeSe-TPGS is introduced to cooperate with a catalytic oxidation process, the gelation rate is remarkably increased, and in a physiological reduction environment, the selenium-containing compound TPGS-SeSe-TPGS can be used for preparing the hydrogel. The disulfide bond can be reduced and broken by glutathione and other reducing agents, so that the controllable degradation of the gel network is realized. In-vitro experiments show that the hydrogel can maintain the structural stability for more than 100 hours in simulated body fluid, and can be completely degraded within 84 hours under the condition of 10mM glutathione. According to the invention, an intelligent gel system with vitamin E biological activity and redox dynamic response is constructed for the first time, and a potential treatment platform is provided for local administration of oxidative stress related diseases.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a preparation method and application of a vitamin E hydrogel with redox properties. Background Art

[0002] In recent years, the adverse health effects of diseases caused by oxidative stress (such as non-alcoholic fatty liver disease, myocardial ischemia-reperfusion injury, and diabetes) have garnered increasing attention, and the development of therapeutic strategies has also attracted significant attention. Vitamin E, a fat-soluble antioxidant, has been shown to mitigate tissue damage and slow disease progression in various oxidative stress-related diseases by neutralizing free radicals and blocking lipid peroxidation chain reactions. However, its clinical efficacy is limited by its low bioavailability and uneven distribution, lack of targeting and selectivity, and the conflict between drug dosage limits and efficacy.

[0003] Hydrogels are materials with a three-dimensional network structure composed of hydrophilic polymers. As drug carriers, they can form a sustained-release reservoir at the site of lesions. They degrade in the body while releasing the drug, maintaining effective drug concentrations at the lesion site for extended periods, making them valuable for the long-term treatment of chronic diseases. To balance the functionality of vitamin E with the advantages of hydrogels as drug carriers, Chinese patent CN104368010A discloses the use of vitamin E polyethylene glycol succinate and its derivatives in the preparation of hydrophilic drug prodrug hydrogel nanoparticle formulations. The vitamin E polyethylene glycol succinate (TPGS) derivative is a vitamin E polyethylene glycol succinate / poly-L-lysine (poly-L-lysine) copolymer (TPGS-PLL). The vitamin E polyethylene glycol succinate / poly-L-lysine copolymer hydrogel nanoparticles achieve co-delivery of cisplatin and polo-like kinase 1 small interfering RNA, achieving a synergistic effect.

[0004] Vitamin E polyethylene glycol succinate (TPGS) and its derivatives have shown great potential in the field of drug delivery due to their amphiphilicity, biodegradability, and excellent biocompatibility. In particular, TPGS, as a water-soluble vitamin E derivative, is not only widely used in the food and pharmaceutical industries as an emulsifier, cosolvent, and additive to enhance bioavailability, but also has the ability to inhibit P-glycoprotein-mediated multidrug resistance, further enhancing the effectiveness of drugs. However, although TPGS and its derivatives have shown great potential in improving drug encapsulation efficiency and oral bioavailability, research on their application in the preparation of prodrug hydrogel nanoparticle formulations of hydrophilic drugs is still limited. In practical applications, the following disadvantages still exist: (1) The prepared hydrogel nanoparticles cannot dynamically adjust their structure and function in response to the complex oxidative environment changes in the body.

[0005] (2) It is impossible to precisely control the drug release rate based on individual differences among patients and different stages of the disease.

[0006] (3) Although it is mentioned that TPGS improves biocompatibility and reduces cytotoxicity, research on the specific degradation process of these hydrogel nanoparticles in the body, the safety of degradation products, and their impact on therapeutic effects is still not in-depth enough. Summary of the Invention

[0007] The present invention aims to provide a method for preparing and applying a redox-responsive vitamin E hydrogel to address the problems of the aforementioned hydrogels, such as their inability to adapt to the complex in vivo environment, dynamically adjust their structure and function, accurately control drug release, and uncontrollable degradation. To address these issues, the present invention has developed a redox-responsive therapeutic hydrogel material (TPGS-Gel) based on vitamin E as a building block. This not only simplifies material design and enhances the therapeutic function of the carrier, but also facilitates coordination between the drug and the carrier, providing a potential therapeutic carrier material for subsequent multi-drug synergistic therapies.

[0008] To achieve the above objectives, the first aspect of the present invention provides a redox-property vitamin E hydrogel, which comprises, by mass percentage, 10.0-30.0 wt% of TPGS-SH, 0-10.0 wt% of TPGS-SeSe-TPGS, and 60-90.0 wt% of a solvent.

[0009] More preferably, the redox vitamin E hydrogel comprises 20.0-25.0 wt % of TPGS-SH and 0-5.0 wt % of TPGS-SeSe-TPGS, calculated by mass percentage.

[0010] Preferably, TPGS-SH is a thiol derivative of vitamin E polyethylene glycol succinate, and TPGS-SH is obtained by reducing TPGS-SS-TPGS.

[0011] Preferably, the preparation method of TPGS-SH is as follows: TPGS (vitamin E polyethylene glycol succinate), SA (succinic acid), and DMAP (4-dimethylaminopyridine) were dissolved in anhydrous dichloromethane and stirred at room temperature for 24 h. After the solvent was completely evaporated in a rotary evaporator, the residue was washed with M w = 1000 dialysis bag, first dialyzed against 1:2 (v / v) ethanol / water solution for 24 h, then dialyzed against deionized water for 48 h to remove excess impurities, and finally the dialyzed liquid was lyophilized to obtain CTPGS; The obtained CTPGS was dissolved in DMSO (dimethyl sulfoxide), and then NHS (N-hydroxysuccinimide) and EDC (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride) were added. After activation, cystamine (bis(2-aminoethyl) disulfide) was added and the reaction was continued for 24 hours. The mixture was placed in M w = 1000 dialysis bag, and then lyophilized to obtain TPGS-SS-TPGS; After obtaining TPGS-SS-TPGS, it was reduced to TPGS-SH by DTT (dithiothreitol), dialyzed against deoxygenated water, and then freeze-dried to obtain TPGS-SH.

[0012] Preferably, the chemical structural formula of TPGS-SH is: ; x is the degree of polymerization, 10<x<100.

[0013] Preferably, the chemical structural formula of TPGS-SeSe-TPGS is: ; x is the degree of polymerization, 10<x<100.

[0014] Preferably, the solvent is at least one of pure water, PBS buffer, and physiological saline.

[0015] A second aspect of the present invention provides a method for preparing a vitamin E hydrogel having redox properties, comprising the following steps: TPGS-SH was added to a solvent containing TPGS-SeSe-TPGS, and the mixture was stirred at 4 degrees Celsius for 2 to 4 hours under anaerobic conditions. After uniform stirring, a vitamin E hydrogel with redox properties was obtained.

[0016] Preferably, the stirring conditions are: stirring at a temperature of 0-8° C. and a rotation speed of 100-200 r / min.

[0017] The third aspect of the present invention provides an application of a vitamin E hydrogel with redox properties, and an application of the vitamin E hydrogel with redox properties in a drug carrier.

[0018] Preferably, the drug-loaded redox vitamin E hydrogel comprises, by weight percentage, 10.0-30.0 wt % of TPGS-SH, 0-10.0 wt % of TPGS-SeSe-TPGS, 0-5.0 wt % of the drug, and 60-90.0 wt % of the solvent.

[0019] More preferably, the drug-loaded redox vitamin E hydrogel comprises 1.0-2.0 wt % of the drug.

[0020] Preferably, the loaded drug can be berberine, doxorubicin, paclitaxel, antibody, etc.

[0021] Therefore, the present invention adopts the above-mentioned preparation method and application of the vitamin E hydrogel with redox properties, which has the following beneficial effects: (1) The TPGS-Gel prepared by the present invention is obtained by oxidizing TPGS, a derivative of vitamin E, to TPGS-SS-TPGS via an oxidant. A stable hydrogel is formed in an aqueous solution through micelle accumulation. The oxidized TPGS-SS-TPGS can be gradually degraded to obtain vitamin E under the action of amidase and hydrolysis reactions in the body. In the treatment of non-alcoholic fatty liver disease (NAFLD), vitamin E can consume reactive oxygen species formed by lipid accumulation in the liver by reducing malondialdehyde (MDA) in the liver and increasing the activity of antioxidant enzymes such as superoxide dismutase (SOD), thereby reducing the damage to the liver caused by oxidative stress and exerting an anti-inflammatory effect. In addition, it can also improve the systemic low-grade inflammatory state by inhibiting the NF-κB signaling pathway and reducing the production of pro-inflammatory factors (TNF-α, IL-6). Finally, vitamin E can also maintain the stability of the liver cell membrane, reduce cell apoptosis caused by lipid peroxidation, and at the same time promote the repair of damaged liver cells and slow down the process of liver fibrosis.

[0022] (2) In the preparation process of TPGS-Gel in the present invention, TPGS-SS-TPGS is used as the main body of the gel, and TPGS-SeSe-TPGS (TPGS-2Se) is added as an enzyme-mimicking catalytic center to improve the gelation behavior of TPGS-Gel. Glutathione peroxidase (GPx) is one of the important members of the body's active oxygen scavenging enzymatic defense line. It can remove peroxides and free radicals in the body, reduce the damage caused by oxidative stress to the body, and enable normal cell function. It plays a vital role in maintaining human health. Selenium is an important component and catalytic center of the GPx enzyme.

[0023] (3) The TPGS-Gel prepared by the present invention degrades to obtain vitamin E, which then plays an antioxidant role and treats non-alcoholic fatty liver disease. Compared with existing drugs for treating fatty liver disease, the redox-property hydrogel precursor of the present invention can produce a two-stage effect of alleviating oxidative stress in the lesion site. After administration, the ROS in the lesion site is consumed while the gel is formed, thereby alleviating oxidative stress in the lesion site. After the hydrogel is formed, the drug burst release can be greatly alleviated, preventing drugs with low solubility and cardiotoxicity from producing adverse reactions after entering the blood. Moreover, the degraded material not only does not produce harmful substances to the human body, but also has a therapeutic effect on the damaged liver. In addition, the introduction of selenium, on the one hand, enables the hydrogel precursor to gel more quickly after in situ injection, avoiding the loss of drug caused by slow gelation; on the other hand, the biomimetic enzyme properties of selenium can be used to remove peroxides and free radicals in the liver, which helps to further reduce the oxidative damage of ROS to the liver.

[0024] (4) The sulfur-containing redox hydrogel TPGS-Gel of the present invention has excellent biocompatibility and antioxidant properties. At the same time, its preparation method is simple and convenient for application and transformation. By modifying antioxidant drugs to form therapeutic hydrogel carrier materials, the present invention not only simplifies the material design and improves the utilization of drugs, but also facilitates the regulation of the linkage relationship and release behavior between drugs and carriers, which is conducive to its further promotion and application.

[0025] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 These are photos of the redox-responsive vitamin E hydrogel obtained in Example 2 before and after gelation; Figure 2 This is a transmission electron micrograph of the hydrogel solution prepared in Example 2; Figure 3 This is a graph showing the rheological properties of the hydrogel prepared in Example 2; Figure 4 The rheological results of the hydrogel precursor obtained in Example 2 after simulated gelation in vitro; Figure 5 The gelation time curve required for the hydrogel precursor obtained in Example 3 at different H2O2 concentrations; Figure 6 Degradation curves of the hydrogel prepared in Example 3 at different GSH concentrations; Figure 7 Drug release curves of the hydrogel prepared in Example 3 at different GSH concentrations; Figure 8 is the cell survival rate at different concentrations of hydrogel raw materials. DETAILED DESCRIPTION

[0027] The present invention will be further described below. It should be noted that this embodiment is based on the technical solution and provides a detailed implementation method and specific operation process, but the present invention is not limited to this embodiment.

[0028] Example 1

[0029] A method for preparing a vitamin E hydrogel comprises the following steps: (1) The preparation method of TPGS-SH comprises the following steps: Accurately weigh 1.0 g TPGS (M w : 1500, purchased from Anhui Zesheng Technology Co., Ltd.) in a round-bottom flask, 5 mL of anhydrous dichloromethane was added thereto for dissolution. After TPGS was completely dissolved, a TPGS solution was obtained. 0.13 g of SA and 0.08 g of DMAP were added to the TPGS solution to obtain a reaction solution. The reaction solution was stirred at room temperature under a nitrogen atmosphere for 24 hours to fully react to obtain a mixed solution. The dichloromethane in the mixed solution was then removed using a rotary evaporator, and the residue was placed in M w =1000 dialysis bags were incubated at room temperature for one day with a 1:2 (v / v) ethanol / water solution. The dialysate was changed every 6 hours to remove excess SA. The samples were then incubated with deionized water for two days, initially changing the deionized water every 6 hours and then every 12 hours on the following day to minimize the removal of residual impurities and ethanol. After dialysis, CTPGS were obtained by freeze-drying.

[0030] After obtaining CTPGS, accurately weigh 0.8 g of CTPGS into a round-bottom flask and dissolve it in 10 mL of DMSO. Once the CTPGS is completely dissolved, a CTPGS solution is obtained. 0.113 g of NHS, 0.15 g of EDC, and 0.14 g of cystamine dihydrochloride (purchased from Anhui Zesheng Technology Co., Ltd.) are added to the CTPGS solution to obtain a mixture. The mixture is stirred at room temperature for 20 hours, then dialyzed and freeze-dried to obtain TPGS-SS-TPGS.

[0031] After obtaining TPGS-SS-TPGS, it was dissolved in ultrapure water and DTT was added (the molar ratio of DTT to TPGS-SS-TPGS was 10:1). It was reduced to TPGS-SH in an oxygen-free environment at 25°C for 8 hours. After dialysis against deoxygenated water, TPGS-SH was freeze-dried.

[0032] 250 mg of TPGS-SH was added to 1 mL of ultrapure water and stirred at 4°C for 12 h to completely dissolve it to obtain a vitamin E hydrogel precursor. 500 µL of the vitamin E hydrogel precursor solution was placed in a small glass bottle and gradually oxidized in the air to obtain a vitamin E hydrogel.

[0033] Example 2

[0034] The difference between this embodiment and embodiment 1 is that ultrapure water is replaced with a 1 mg / mL TPGS-SeSe-TPGS solution.

[0035] The vitamin E hydrogel prepared in Example 2 was characterized.

[0036] 2 mg of the hydrogel prepared in Example 2 was dissolved in 2 mL of ultrapure water and stirred thoroughly, then ultrasonicated for 30 min to obtain a hydrogel solution. 50 μL of the hydrogel solution was sampled on a copper mesh, and the sample was tested under a transmission microscope to obtain the main composition of the hydrogel. Figure 2 As can be seen, the gel prepared in Example 2 is composed of some dispersed, approximately spherical particles. This is because TPGS-SS-TPGS obtained by oxidation of TPGS-SH self-assembles into micelles in the aqueous solution, which is beneficial to improving drug solubility and enhancing structural stability.

[0037] The rheological properties of the hydrogel prepared in Example 2 were tested, and the test results are shown in Figure 3 ,from Figure 3 It can be seen that the storage modulus of the hydrogel is more than one order of magnitude larger than the loss modulus, and the mechanical properties of the hydrogel do not change with time, indicating that the sulfur-containing redox hydrogel TPGS-Gel prepared in Example 2 has stable mechanical properties.

[0038] Example 3

[0039] A method for preparing a vitamin E hydrogel comprises the following steps: The preparation method of TPGS-SH is the same as that in Example 1.

[0040] Add 250 mg of TPGS-SH to a 1 mL glass bottle containing TPGS-SeSe-TPGS (1 mg / mL), stir at 4°C to completely dissolve it to obtain a hydrogel precursor solution, take 400 µL of the hydrogel precursor solution and place it in a new glass bottle, mix it thoroughly with 100 µL of 100 mM H2O2 solution, and place it on a rotational rheometer to test the modulus change during the in vitro simulated gelation process.

[0041] The gelling process in Example 3 was monitored. Figure 4The rheological study results of the hydrogel precursor obtained in Example 3 under the in vitro simulated ROS environment in vivo are shown in Figure 3. Figure 4 It can be seen that at the beginning, the storage modulus is smaller than the loss modulus and it is in a sol-like state. Under the action of H2O2, the storage modulus gradually exceeds the loss modulus after 376s, indicating that the sulfur-containing redox hydrogel can form a gel under the action of an oxidant.

[0042] Example 4

[0043] The gelling properties of TPGS-SH under different environments were tested. The testing process is as follows: 1000 mg TPGS-SH (made by M w =1.5 kDa TPGS (prepared) was added to 3.6 mL of ultrapure water and stirred at 4°C until completely dissolved to obtain a clear solution. This solution was divided equally into two portions, designated TPGS-SH and TPGS-SH+Se. 4 mg of TPGS-SeSe-TPGS was then added to the TPGS-SH+Se mixture and stirred at 4°C until completely dissolved to obtain a clear solution. Take 18 glass bottles, add 90µL of the prepared solution to each glass bottle, and divide them into 6 groups, namely A, A + 1mM H2O2, A + 10mM H2O2, B, B + 1mM H2O2, B + 10mM H2O2. Set up three parallel groups in each group. Add 10µL of ultrapure water to groups A and B, add 9µL of ultrapure water and 1µL of 100mM H2O2 to A + 1mM H2O2 and B + 1mM H2O2, and add 10µL of 100mM H2O2 to A + 10mM H2O2 and B + 10mM H2O2. Place them in a shaker at 37℃ and 72rpm / min, and observe whether they form gel every 0.5h. Test results are shown in Figure 5 The results showed that the gelation time of group B was shorter than that of group A, which indicates that the redox-responsive vitamin E hydrogel of the present invention has good ROS responsiveness. The specific grouping and gelation time are shown in Table 1.

[0044] Table 1 Gelation time test results Group TPGS-SH Ultrapure water TPGS-SeSe-TPGS Ultrapure water <![CDATA[100mM H2O2]]> Gelation time / h A 25mg 90µL - 10µL - 20.33 <![CDATA[A+1mM H2O2]]> 25mg 90µL - 9µL 1µL 19 <![CDATA[A+10mM H2O2]]> 25mg 90µL - - 10µL 6.17 B 25mg 90µL 0.1mg 10µL - 16.33 <![CDATA[B+1mM H2O2]]> 25mg 90µL 0.1mg 9µL 1µL 7.83 <![CDATA[B+10mM H2O2]]> 25mg 90µL 0.1mg - 10µL 3.83 The precursors of solutions A and B prepared in this example were placed in air for natural oxidation. After the oxidation was complete, the hydrogel degradation behavior was studied in PBS solution and 10mM glutathione (GSH) solution. Figure 6 As shown in the figure, the redox-responsive vitamin E hydrogel can be maintained for more than 100 h under PBS solution conditions, while the degradation rate is faster under low GSH concentration conditions.

[0045] At the same time, drug release studies conducted under the same conditions by loading berberine hydrochloride (provided by Anhui Zesheng Technology Co., Ltd.) into the gel showed that in an environment simulating low GSH concentrations in the body, the drug release rate of the hydrogel also accelerated simultaneously, thereby achieving on-demand release of drugs at the lesion site. Figure 7 The drug release profile of the hydrogel was demonstrated to further verify this result.

[0046] Example 5

[0047] 125.0 mg TPGS-SH (by M w =1.5kDa TPGS (prepared) was added to 500µL of ultrapure water and stirred in an ice-water bath until a clear solution was obtained. The solution was then fully oxidized in air for 24 hours to obtain a redox-responsive vitamin E hydrogel.

[0048] Example 6

[0049] 214.3 mg TPGS-SH (by M w =1.5kDa TPGS (prepared) was added to 500µL of ultrapure water and stirred in an ice-water bath until a clear solution was obtained. The solution was then fully oxidized in air for 24 hours to obtain a redox-responsive vitamin E hydrogel.

[0050] Example 7

[0051] 300.0 mg TPGS-SH (made by M w =1.5kDa TPGS was added to 500µL of ultrapure water and stirred in an ice-water bath. After 24 hours, no clear solution was obtained.

[0052] Example 8

[0053] 88.2 mg TPGS-SH (by M w =1.5kDa TPGS was added to 500µL of ultrapure water and stirred in an ice-water bath until clear. The mixture was fully oxidized in air. However, no hydrogel was obtained after long-term observation.

[0054] As can be seen from Examples 5 to 8, the change in the amount of TPGS-SH added will affect the preparation of the hydrogel. When the amount of TPGS-SH added is too little, no hydrogel can be obtained. When the amount of TPGS-SH added is too much, no clear solution can be obtained as a precursor.

[0055] Example 9

[0056] 88.2 mg TPGS-SH (by M w=3.5kDa TPGS was added to 500µL ultrapure water, stirred in an ice-water bath until clear, and fully oxidized in air to obtain a hydrogel.

[0057] Example 10

[0058] 125.0 mg of TPGS-SH was added to 500 µL of ultrapure water containing TPGS-SeSe-TPGS (1.0 mg / mL) and stirred in an ice-water bath until uniformly dispersed. 10 µL of 10 mM H2O2 solution was then added. After 6 hours of reaction on a shaker, a hydrogel was obtained, significantly shortening the gelation time.

[0059] Example 11

[0060] Replace TPGS-SH with TPGS (M w =1.5kDa), 100µL of 20wt% TPGS solution was prepared with ultrapure water, stirred at 4°C until a clear solution was obtained, and then 10µL of 10mM H2O2 solution was added. After long-term observation, no hydrogel was obtained.

[0061] From the results of Example 11, it can be seen that when TPGS-SH is replaced with TPGS (1.5 kDa), no corresponding hydrogel can be formed. This shows that the use of TPGS-SH in the present invention has special gel-forming properties, that is, TPGS-SH can form an amphiphilic triblock compound of TPGS-SS-TPGS with twice the molecular weight under environmental oxidation, thereby forming a hydrogel. However, TPGS does not have a thiol group and does not have oxidative crosslinking properties, and thus cannot be used to prepare a hydrogel.

[0062] Example 12

[0063] HepG2 human liver cancer cells (1×10 4 Cells were plated in 96-well plates and cultured overnight. Different doses of TPGS-SH and BBR (berberine hydrochloride) were added to the plates and incubated for 24 hours. The cell viability was then determined by MTT colorimetry (n=3). Figure 8 This shows that TPGS-SH and BBR as drugs have no obvious toxicity to hepatocytes.

[0064] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit the same. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that they can still modify or replace the technical solutions of the present invention with equivalents, and these modifications or equivalent replacements cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A redox-sensitive vitamin E hydrogel, characterized by: Calculated by mass percentage, the redox vitamin E hydrogel includes 10.0-30.0 wt% of TPGS-SH, 0-10.0 wt% of TPGS-SeSe-TPGS, and 60-90.0 wt% of solvent.

2. The redox-sensitive vitamin E hydrogel according to claim 1, wherein: TPGS-SH is obtained by reducing TPGS-SS-TPGS.

3. The redox-sensitive vitamin E hydrogel according to claim 1, wherein: The chemical structure of TPGS-SH is: ； x is the degree of polymerization, 10<x<100.

4. The redox-sensitive vitamin E hydrogel according to claim 1, wherein: The chemical structure of TPGS-SeSe-TPGS is: ； x is the degree of polymerization, 10<x<100.

5. The redox-sensitive vitamin E hydrogel according to claim 1, wherein: The solvent is at least one of pure water, PBS buffer, and physiological saline.

6. The method for preparing a redox-sensitive vitamin E hydrogel according to any one of claims 1 to 5, wherein: The following steps are involved: TPGS-SH was added to a solvent containing TPGS-SeSe-TPGS, and the mixture was stirred at 4 degrees Celsius for 2 to 4 hours under anaerobic conditions. After uniform stirring, a vitamin E hydrogel with redox properties was obtained.

7. The method for preparing a redox-sensitive vitamin E hydrogel according to claim 6, wherein: The stirring conditions are: stirring at a speed of 100-200 r / min at a temperature of 0-8°C.

8. The use of a redox-sensitive vitamin E hydrogel according to any one of claims 1 to 5, characterized in that: Application of redox-property vitamin E hydrogel in drug delivery.

9. The use of a redox-sensitive vitamin E hydrogel according to claim 8, characterized in that: According to mass percentage, the redox-property vitamin E hydrogel loaded with drugs includes 10.0-30.0 wt% of TPGS-SH, 0-10.0 wt% of TPGS-SeSe-TPGS, 0-5.0 wt% of drugs and 60-90.0 wt% of solvent.

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