Silk fibroin-loaded hydrogel liposome with transdermal delivery effect as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of biological materials, and particularly relates to silk fibroin-loaded hydrogel lipidosome with a transdermal delivery effect as well as a preparation method and application of the silk fibroin-loaded hydrogel lipidosome. The preparation method comprises the following steps: dissolving degummed silk in a neutral salt solution to obtain a silk fibroin solution, and dialyzing and filtering to obtain a silk fibroin aqueous solution; then carrying out diazo coupling reaction on the silk fibroin aqueous solution to obtain an azide functionalized silk fibroin aqueous solution; dissolving phospholipid and cholesterol in a solvent to obtain a mixed solution; adding the azide functionalized silk fibroin aqueous solution into the mixed solution, and carrying out ultrasonic emulsification to obtain an emulsion; the emulsion is sequentially subjected to reverse evaporation treatment, and gelated silk fibroin loaded liposome is obtained; and carrying out freeze drying on the gelated silk fibroin loaded liposome to obtain the silk fibroin loaded hydrogel liposome with a transdermal delivery effect.

Description

Technical Field

[0001] The invention belongs to the technical field of biomaterials, and particularly relates to a silk fibroin hydrogel liposome with transdermal delivery effect, a preparation method and an application thereof. Background Art

[0002] The skin, the largest and most accessible organ in the human body, plays a vital role in maintaining homeostasis, defending against invading microorganisms, and protecting against environmental insults such as heat, chemicals, and toxins. Transdermal drug delivery can deliver bioactive agents through the skin for local or systemic effects. It is non-invasive and can be self-administered. Transdermal delivery systems have become a cutting-edge topic in the research of delivering small molecule drugs, proteins, small peptide molecules, and vaccines. They can avoid the influence of the "first-pass effect" in the liver and gastrointestinal tract, maintain stable and continuous drug plasma concentrations, reduce the frequency of dosing, and improve drug bioavailability.

[0003] A Chinese patent (publication number CN119280079A) discloses a method for preparing liposomes containing hair growth active ingredients. This invention utilizes active ingredients to regulate hormone levels, improve scalp blood circulation, and stimulate anti-hair loss factors, thereby promoting hair growth in multiple ways. Furthermore, the liposomes, formed from lecithin and oil-soluble active ingredients, are integrated to encapsulate the active ingredients. This overcomes the weakness of the active ingredients' poor transdermal ability due to large differences in water solubility, improves the stability and bioavailability of the active ingredients, and significantly enhances the hair growth and development effects of the prepared liposomes containing hair growth active ingredients. However, prior research on the use of silk fibroin to prepare hydrogel liposomes and their application in transdermal delivery systems remains insufficient.

[0004] Therefore, how to use silk fibroin as raw material, perform functional treatment on it, use it together with phospholipids and cholesterol to prepare silk fibroin hydrogel liposomes, and successfully apply it to transdermal delivery systems has become a direction that needs to be studied. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of the present invention is to provide a silk fibroin hydrogel liposome with transdermal delivery effect and its preparation method and application. Silk fibroin is used as raw material, and it is subjected to diazo coupling treatment to obtain azide-functionalized silk fibroin, which is used together with phospholipids and cholesterol. Through reverse evaporation and ultrasonic treatment, the silk fibroin hydrogel liposome is prepared and successfully applied to the transdermal delivery system.

[0006] The technical solutions adopted by the present invention to solve the above technical problems are as follows: The first aspect of the present invention provides a method for preparing a silk fibroin hydrogel liposome having a transdermal delivery effect, characterized in that the method comprises the following steps: S1: dissolving the degummed silk in a neutral salt solution to obtain a silk fibroin solution, dialysis filtering, and obtaining a silk fibroin aqueous solution; then performing a diazo coupling reaction on the silk fibroin aqueous solution to obtain an azide-functionalized silk fibroin aqueous solution; S2: dissolving phospholipid and cholesterol in a solvent to obtain a mixed solution; S3: adding the azide-functionalized silk fibroin aqueous solution to the mixed solution for ultrasonic emulsification to obtain an emulsion; S4: performing reverse evaporation treatment on the emulsion in sequence to obtain gelled silk fibroin protein liposomes; S5: freeze-drying the gelled silk fibroin liposomes to obtain silk fibroin hydrogel liposomes with transdermal delivery effect.

[0007] The following are preferred technical solutions of the present invention, but are not intended to limit the technical solutions provided by the present invention. Through the following preferred technical solutions, the objectives and beneficial effects of the present invention can be better achieved and realized.

[0008] As a preferred technical solution of the present invention, the diazo coupling reaction step includes: dissolving 0.6-0.8 parts of 4-azidoaniline hydrochloride in a mixture of 4-6 parts of acetonitrile and 4-6 parts of deionized water, then adding 4-6 parts of 0.01-0.02 mol / L hydrochloric acid aqueous solution and mixing evenly, placing in an ice bath to control the temperature to 0-5°C, and then slowly adding dropwise 4-6 parts of 0.06-0.08 mol / L sodium nitrite aqueous solution and stirring for 10-20 minutes to obtain a diazonium salt solution; adjusting the pH of 90-100 parts of silk fibroin aqueous solution to 7-8 with borate buffer, and then slowly adding 20-24 parts of the diazonium salt solution under light-proof and ice bath conditions and stirring for 2-4 hours, terminating the reaction and then dialysis purification.

[0009] The nanofiber structure of azidated silk fibroin simulates the natural channels of the skin and, combined with the lipid bilayer of liposomes, can reduce the lipid order in the stratum corneum and improve the efficiency of transdermal delivery. At the same time, azidated silk fibroin can be anchored to the surface of liposomes through click chemistry to form a "protein-phospholipid bilayer" mixed membrane, thereby enhancing the penetration of liposomes into the skin barrier.

[0010] As a preferred technical solution of the present invention, the neutral salt solution in step S1 is a binary system of lithium bromide / water or a ternary system of calcium chloride / ethanol / water.

[0011] As a preferred technical solution of the present invention, the molar ratio of lithium bromide:water in the lithium bromide / water binary system is 1:5; the molar ratio of calcium chloride:ethanol:water in the calcium chloride / ethanol / water ternary system is 1:2:8.

[0012] As a preferred technical solution of the present invention, the dissolution temperature in step S1 is 50-70° C., and the dissolution time is 4-6 hours.

[0013] As a preferred technical solution of the present invention, the mass concentration of the silk fibroin aqueous solution in step S1 is 2-4%.

[0014] The neutral salt solution of the present invention is a lithium bromide / water binary system or a calcium chloride / ethanol / water ternary system. The lithium bromide / water binary system destroys the beta-folded structure of silk fibroin and converts it into a soluble random coil conformation, thereby achieving rapid dissolution. The calcium ions of the calcium chloride / ethanol / water ternary system can destroy the ionic bonds and hydrogen bonds of the silk fibroin and attack the crystalline region. The ethanol reduces the polarity of water and enhances the penetration into the hydrophobic region, while inhibiting the oxidative degradation of the protein during the dissolution process. The ternary system can achieve efficient dissolution under mild conditions.

[0015] As a preferred technical solution of the present invention, the phospholipid in step S2 is selected from any one or more of egg yolk lecithin, soybean lecithin, dipalmitoylphosphatidylcholine, and distearoylphosphatidylcholine.

[0016] As a preferred technical solution of the present invention, the concentration of phospholipids in the mixed solution of step S2 is 1-20 mg / mL, and the concentration of cholesterol in the mixed solution is 0.2-2 mg / mL.

[0017] As a preferred technical solution of the present invention, the organic solvent in step S2 is chloroform or dichloromethane.

[0018] The phospholipid-cholesterol composite membrane is similar to the lipids in the stratum corneum, which can promote the fusion of liposomes with the skin barrier and make silk fibroin diffuse more easily into the deep layers of the skin. The presence of cholesterol can enhance the moisturizing ability of liposomes, soften the stratum corneum through hydration, expand the intercellular space, and promote the penetration of active ingredients.

[0019] As a preferred technical solution of the present invention, the volume ratio of the azide-functionalized silk fibroin aqueous solution to the mixed solution in step S3 is 1:(5-10).

[0020] As a preferred technical solution of the present invention, the ultrasonic time in step S3 is 10 to 30 seconds, and the number of ultrasonic times is 1 to 3 times.

[0021] As a preferred technical solution of the present invention, the reverse evaporation treatment step in step S4 includes: transferring the emulsion to a rotary evaporator, rotary evaporating at a speed of 50-80 rpm at 30-60°C for 6-24 hours to obtain a silk fibroin liposome film; adding 4-6 parts of phosphate buffer solution to the silk fibroin liposome film, incubating at 25-40°C for 2-8 hours, and then ultrasonically treating to induce silk fibroin gelation.

[0022] As a preferred technical solution of the present invention, the ultrasonic treatment time is 10 to 30 minutes, and the number of ultrasonic treatments is 1 to 3 times.

[0023] As a preferred technical solution of the present invention, the freeze-drying conditions in step S5 include: a temperature of -20 to -40°C and a time of 36 to 48 hours.

[0024] As a preferred technical solution of the present invention, the particle size of the silk fibroin hydrogel liposome with transdermal delivery effect is 90-100 nm, and the zeta potential is -9.4--9.6 mV.

[0025] The second aspect of the present invention provides a silk fibroin hydrogel liposome with transdermal delivery effect prepared by the method described in the first aspect.

[0026] The third aspect of the present invention provides a use of the silk fibroin hydrogel liposome with transdermal delivery effect prepared by the method described in the first aspect in skin care products.

[0027] Compared with the prior art, the present invention has the following beneficial effects: (1) The silk fibroin raw material of the present invention has good compatibility, is degradable, has excellent mechanical properties and film-forming properties, and can enhance the stability of liposomes; silk fibroin liposomes are simply and efficiently prepared by reverse evaporation, ultrasonic treatment and other methods, and the liposomes can effectively penetrate the stratum corneum of the skin, solving the problem that large-molecule silk fibroin is difficult to penetrate the stratum corneum of the skin.

[0028] (2) The neutral salt solution of the present invention is a lithium bromide / water binary system or a calcium chloride / ethanol / water ternary system, wherein the lithium bromide / water binary system destroys the β-folded structure of silk fibroin and converts it into a soluble random coil conformation, thereby achieving rapid dissolution; the calcium ions of the calcium chloride / ethanol / water ternary system can destroy the ionic bonds and hydrogen bonds of silk fibroin and attack the crystalline region, and the ethanol reduces the polarity of water and enhances the penetration into the hydrophobic region, while inhibiting the oxidative degradation of the protein during the dissolution process. The ternary system can achieve efficient dissolution under mild conditions.

[0029] (3) The nanofiber structure of azidated silk fibroin simulates the natural channels of the skin and, in combination with the lipid bilayer of liposomes, can reduce the lipid order in the stratum corneum and improve the efficiency of transdermal delivery. At the same time, azidated silk fibroin can be anchored to the surface of liposomes through click chemistry to form a "protein-phospholipid bilayer" mixed membrane, thereby enhancing the penetration of liposomes into the skin barrier. DETAILED DESCRIPTION

[0030] For the convenience of understanding the present invention, the present invention is given below with examples. It should be understood by those skilled in the art that the examples are only for the purpose of helping to understand the present invention and should not be regarded as specific limitations of the present invention.

[0031] The sources of some components in the Examples and Comparative Examples are as follows: Lithium bromide, CAS No. 7550-35-8, was purchased from Shanghai MacLean Biochemical Technology Co., Ltd.; Calcium chloride, CAS No. 10043-52-4, was purchased from Shanghai MacLean Biochemical Technology Co., Ltd.; 4-Azidoaniline hydrochloride, CAS No. 91159-79-4, was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; p-Toluenesulfonic acid, CAS No. 104-15-4, was purchased from Sinopharm Chemical Reagent Co., Ltd.; Sodium nitrite, CAS No. 7632-00-0, was purchased from Sinopharm Chemical Reagent Co., Ltd.; Borate buffer, product number B407195, was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; Egg yolk lecithin, product number L305002, was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.; Soybean lecithin, CAS number 8002-43-5, was purchased from Shaanxi New Horizon Biotechnology Co., Ltd.; Dipalmitoylphosphatidylcholine, product number S26236, was purchased from Shanghai Yuanye Biotechnology Co., Ltd.; Distearoylphosphatidylcholine, product number S50960, was purchased from Shanghai Yuanye Biotechnology Co., Ltd.; Cholesterol, CAS No. 57-88-5, was purchased from Sinopharm Chemical Reagent Co., Ltd.

[0032] Example 1 This embodiment provides a method for preparing silk fibroin hydrogel liposomes with transdermal delivery effect, characterized by comprising the following steps: S1: 10 parts of degummed silk were dissolved (temperature 65°C, time 4h) in 40 parts of lithium bromide / water binary system (lithium bromide:water molar ratio is 1:5) to obtain a silk fibroin solution, which was dialyzed for 3 days and then filtered to obtain a silk fibroin aqueous solution with a mass concentration of 3%; 0.8 parts of 4-azidoaniline hydrochloride were dissolved in a mixture of 6 parts of acetonitrile and 6 parts of deionized water, and then 6 parts of 0.01~0.02 mol / L hydrochloric acid aqueous solution were added and mixed evenly, placed in an ice bath to control the temperature to 0°C, and then 6 parts of 0.08 mol / L sodium nitrite aqueous solution were slowly added dropwise and stirred for 20 min to obtain a diazonium salt solution; 100 parts of the silk fibroin aqueous solution were adjusted to pH 8 with borate buffer, and then 24 parts of the diazonium salt solution were slowly added under light-proof and ice bath conditions and stirred for 4h. After terminating the reaction, the solution was dialyzed and purified to obtain an azide-functionalized silk fibroin aqueous solution; S2: dissolving egg yolk lecithin and cholesterol in chloroform to obtain a mixed solution (the concentration of egg yolk lecithin in the mixed solution is 20 mg / mL, and the concentration of cholesterol in the mixed solution is 2 mg / mL); S3: adding one part of the azide-functionalized silk fibroin aqueous solution to five parts of the mixed solution and performing ultrasonic emulsification (for 15 seconds and twice) to obtain an emulsion; S4: The emulsion was transferred to a rotary evaporator, and the emulsion was rotary evaporated at 60 rpm at 50° C. for 8 h to obtain a silk fibroin liposome film; 5 parts of phosphate buffer solution was added to the silk fibroin liposome film, and the film was incubated at 40° C. for 2 h, and then ultrasonicated (for 10 min, 3 times) to induce gelation of the silk fibroin, thereby obtaining gelated silk fibroin liposomes; S5: freeze-drying the gelled silk fibroin liposomes (temperature: -20°C, time: 48 h) to obtain silk fibroin hydrogel liposomes with transdermal delivery effect (particle size: 100 nm, zeta potential: -9.6 mV).

[0033] Example 2 This embodiment provides a method for preparing silk fibroin hydrogel liposomes with transdermal delivery effect, characterized by comprising the following steps: S1: 10 parts of degummed silk were dissolved (temperature 70°C, time 4h) in a calcium chloride / ethanol / water ternary system (molar ratio of calcium chloride:ethanol:water was 1:2:8) to obtain a silk fibroin solution, which was then dialyzed and filtered to obtain a silk fibroin aqueous solution with a mass concentration of 2%; 0.6 parts of 4-azidoaniline hydrochloride were dissolved in a mixture of 4 parts of acetonitrile and 4 parts of deionized water, and then 4 parts of 0.01mol / L hydrochloric acid aqueous solution were added and mixed evenly, and the mixture was placed in an ice bath to control the temperature to 5°C, and then 4 parts of 0.06mol / L sodium nitrite aqueous solution were slowly added dropwise and stirred for 10min to obtain a diazonium salt solution; 90 parts of the silk fibroin aqueous solution were adjusted to pH 7 with borate buffer, and then 20 parts of the diazonium salt solution were slowly added in the dark and ice bath conditions and stirred for 2h. After terminating the reaction, the mixture was dialyzed and purified to obtain an azide-functionalized silk fibroin aqueous solution; S2: dissolving soybean lecithin and cholesterol in dichloromethane to obtain a mixed solution (the concentration of soybean lecithin in the mixed solution is 1 mg / mL, and the concentration of cholesterol in the mixed solution is 0.2 mg / mL); S3: adding 1 part of the azide-functionalized silk fibroin aqueous solution to 10 parts of the mixed solution and performing ultrasonic emulsification (time is 20 seconds, number of times is 2 times) to obtain an emulsion; S4: The emulsion was transferred to a rotary evaporator, and the emulsion was rotary evaporated at 50 rpm at 60° C. for 6 h to obtain a silk fibroin liposome film; 4 parts of phosphate buffer solution were added to the silk fibroin liposome film, and the film was incubated at 25° C. for 8 h, and then ultrasonicated (for 30 min, once) to induce gelation of the silk fibroin, thereby obtaining gelated silk fibroin liposomes; S5: freeze-drying the gelled silk fibroin liposomes (temperature: -40°C, time: 36 h) to obtain silk fibroin hydrogel liposomes with transdermal delivery effect (particle size: 90 nm, zeta potential: -9.4 mV).

[0034] Example 3 This embodiment provides a method for preparing silk fibroin hydrogel liposomes with transdermal delivery effect, characterized by comprising the following steps: S1: Dissolve 10 parts of degummed silk (temperature 50°C, time 6 hours) in 50 parts of lithium bromide / water binary system (lithium bromide:water molar ratio is 1:5) to obtain a silk fibroin solution, and filter and dialysis to obtain a silk fibroin aqueous solution with a mass concentration of 4%; dissolve 0.7 parts of 4-azidoaniline hydrochloride in a mixture of 5 parts of acetonitrile and 5 parts of deionized water, then add 5 parts of 0.015 mol / L hydrochloric acid aqueous solution and mix evenly, place in an ice bath to control the temperature at 4°C, and then slowly add 5 parts of 0.07 mol / L sodium nitrite aqueous solution and stir for 15 minutes to obtain a diazonium salt solution; adjust the pH of 95 parts of silk fibroin aqueous solution to 7.4 with borate buffer, then slowly add 22 parts of the diazonium salt solution in the dark and ice bath conditions and stir for 3 hours, terminate the reaction and dialysis and purification to obtain an azide-functionalized silk fibroin aqueous solution; S2: dissolving phospholipids (egg yolk lecithin, soybean lecithin, dipalmitoylphosphatidylcholine, distearoylphosphatidylcholine) and cholesterol in chloroform to obtain a mixed solution (the concentration of phospholipids in the mixed solution is 1 mg / mL, and the concentration of cholesterol in the mixed solution is 0.2 mg / mL); S3: adding 3 parts of the azide-functionalized silk fibroin aqueous solution to 10 parts of the mixed solution and performing ultrasonic emulsification (time is 30 seconds, number of times is 1) to obtain an emulsion; S4: The emulsion was transferred to a rotary evaporator, and rotary evaporated at 80 rpm at 30° C. for 24 h to obtain a silk fibroin liposome film; 4 parts of phosphate buffer solution were added to the silk fibroin liposome film, and the film was incubated at 30° C. for 6 h, and then ultrasonicated (for 10 min, 3 times) to induce gelation of the silk fibroin, thereby obtaining gelated silk fibroin liposomes; S5: freeze-drying the gelled silk fibroin liposomes (temperature: -30°C, time: 40 h) to obtain silk fibroin hydrogel liposomes with transdermal delivery effect (particle size: 95 nm, zeta potential: -9.5 mV).

[0035] Comparative Example 1 This embodiment provides a method for preparing hydrogel liposomes, characterized in that it includes the following steps: S1: Dissolve 10 parts of degummed silk (temperature 65°C, time 4 hours) in 40 parts of lithium bromide / water binary system (lithium bromide:water molar ratio 1:5) to obtain a silk fibroin solution. After dialysis for 3 days, filter and obtain a silk fibroin aqueous solution with a mass concentration of 3%; S2: dissolving egg yolk lecithin and cholesterol in chloroform to obtain a mixed solution (the concentration of egg yolk lecithin in the mixed solution is 20 mg / mL, and the concentration of cholesterol in the mixed solution is 2 mg / mL); S3: adding 1 part of the silk fibroin aqueous solution to 5 parts of the mixed solution and performing ultrasonic emulsification (time is 15 seconds, number of times is 2) to obtain an emulsion; S4: The emulsion was transferred to a rotary evaporator, and the emulsion was rotary evaporated at 60 rpm at 50° C. for 8 h to obtain a silk fibroin liposome film; 5 parts of phosphate buffer solution was added to the silk fibroin liposome film, and the film was incubated at 40° C. for 2 h, and then ultrasonicated (for 10 min, 3 times) to induce gelation of the silk fibroin, thereby obtaining gelated silk fibroin liposomes; S5: freeze-drying the gelled silk fibroin liposomes (temperature: -20°C, time: 48 h) to obtain hydrogel liposomes (particle size: 180 nm, zeta potential: -10.6 mV).

[0036] The transdermal delivery performance of the hydrogel liposomes provided in the above examples and comparative examples was tested using the following method: In vitro transdermal delivery was tested using a Franz diffusion cell. Prior to the experiment, pig ear skin was naturally thawed in saline and cleaned, followed by blotting with filter paper to remove moisture from the skin surface. The skin was then fixed, and 6.5 mL of PBS and 0.5 mL of bispecific antibody were added to the receiving cell. Air bubbles were removed to allow contact with the skin. The receiving solution was stirred at 37°C and 350 rpm under constant magnetic stirring. 2 mL of hydrogel liposomes was placed in the donor cell as the experimental group. At predetermined time intervals (1, 3, 6, 9, 12, and 24 hours), 2 mL of the receiving cell fluid was collected from the receiving cell and an equal amount of PBS was added. Air bubbles were removed to allow contact with the skin. The collected receiving cell fluid was filtered through a 0.22 μm filter membrane into a liquid phase vial and analyzed by HPLC. The unit cumulative permeation was calculated.

[0037] The above performance test data is shown in Table 1.

[0038] Table 1 Performance test results

[0039] From the above content, it can be seen that the present invention uses silk fibroin as raw material and performs diazo coupling treatment on it to obtain azide-functionalized silk fibroin, which is used together with phospholipids and cholesterol. Through reverse evaporation and ultrasonic treatment, silk fibroin-loaded hydrogel liposomes are prepared and successfully applied to the transdermal delivery system.

Claims

1. A method for preparing silk fibroin hydrogel liposomes with transdermal delivery effect, characterized in that: The following steps are involved: S1: dissolving the degummed silk in a neutral salt solution to obtain a silk fibroin solution, dialysis filtering, and obtaining a silk fibroin aqueous solution; then performing a diazo coupling reaction on the silk fibroin aqueous solution to obtain an azide-functionalized silk fibroin aqueous solution; S2: dissolving phospholipid and cholesterol in a solvent to obtain a mixed solution; S3: adding the azide-functionalized silk fibroin aqueous solution to the mixed solution for ultrasonic emulsification to obtain an emulsion; S4: performing reverse evaporation treatment on the emulsion in sequence to obtain gelled silk fibroin protein liposomes; S5: freeze-drying the gelled silk fibroin liposomes to obtain silk fibroin hydrogel liposomes with transdermal delivery effect.

2. The method for preparing a silk fibroin hydrogel liposome with transdermal delivery effect according to claim 1, characterized in that: The diazo coupling reaction comprises the following steps: dissolving 0.6-0.8 parts of 4-azidoaniline hydrochloride in a mixture of 4-6 parts of acetonitrile and 4-6 parts of deionized water, then adding 4-6 parts of a 0.01-0.02 mol / L hydrochloric acid aqueous solution and mixing evenly, placing the mixture in an ice bath and controlling the temperature at 0-5°C, then slowly dropwise adding 4-6 parts of a 0.06-0.08 mol / L sodium nitrite aqueous solution and stirring for 10-20 minutes to obtain a diazonium salt solution; adjusting the pH of 90-100 parts of a silk fibroin aqueous solution to 7-8 with a borate buffer, then slowly adding 20-24 parts of the diazonium salt solution in the dark and in an ice bath, stirring for 2-4 hours, terminating the reaction, and then dialysis purification.

3. The method for preparing a silk fibroin hydrogel liposome with transdermal delivery effect according to claim 1, characterized in that: The neutral salt solution in step S1 is a binary system of lithium bromide / water or a ternary system of calcium chloride / ethanol / water; The molar ratio of lithium bromide to water in the lithium bromide / water binary system is 1:5; the molar ratio of calcium chloride to ethanol to water in the calcium chloride / ethanol / water ternary system is 1:2:

8.

4. The method for preparing a silk fibroin hydrogel liposome with transdermal delivery effect according to claim 1, characterized in that: In step S2, the phospholipid is selected from any one or more of egg yolk lecithin, soybean lecithin, dipalmitoylphosphatidylcholine, and distearoylphosphatidylcholine; The concentration of phospholipids in the mixed solution of step S2 is 1-20 mg / mL, and the concentration of cholesterol in the mixed solution is 0.2-2 mg / mL.

5. The method for preparing a silk fibroin hydrogel liposome with transdermal delivery effect according to claim 1, characterized in that: In step S3, the volume ratio of the azide-functionalized silk fibroin aqueous solution to the mixed solution is 1:(5-10); The ultrasonic time in step S3 is 10 to 30 seconds, and the number of ultrasonic times is 1 to 3 times.

6. The method for preparing a silk fibroin hydrogel liposome with transdermal delivery effect according to claim 1, characterized in that: The reverse evaporation treatment in step S4 includes: transferring the emulsion to a rotary evaporator, and rotary evaporating at a speed of 50-80 rpm at 30-60° C. for 6-24 hours to obtain a silk fibroin liposome film; adding 4-6 parts of phosphate buffer solution to the silk fibroin liposome film, incubating at 25-40° C. for 2-8 hours, and then ultrasonically treating to induce silk fibroin gelation.

7. The method for preparing a silk fibroin hydrogel liposome with transdermal delivery effect according to claim 1, characterized in that: The freeze-drying conditions in step S5 include: a temperature of -20 to -40°C and a time of 36 to 48 hours.

8. The method for preparing a silk fibroin hydrogel liposome with transdermal delivery effect according to claim 1, characterized in that: The particle size of the silk fibroin hydrogel liposome with transdermal delivery effect is 90-100 nm, and the zeta potential is -9.4--9.6 mV.

9. A silk fibroin hydrogel liposome with transdermal delivery effect, characterized in that: The method is obtained by the preparation method according to any one of claims 1 to 8.

10. Use of the silk fibroin hydrogel liposome with transdermal delivery effect obtained by the preparation method according to any one of claims 1 to 8 in skin care products.

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