CN117338988A - Astaxanthin-loaded silk fiber wound repair film and preparation method and application thereof - Google Patents
Astaxanthin-loaded silk fiber wound repair film and preparation method and application thereof Download PDFInfo
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- CN117338988A CN117338988A CN202311485193.XA CN202311485193A CN117338988A CN 117338988 A CN117338988 A CN 117338988A CN 202311485193 A CN202311485193 A CN 202311485193A CN 117338988 A CN117338988 A CN 117338988A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
Abstract
The invention provides an astaxanthin-loaded silk fiber wound repair film and a preparation method and application thereof, and belongs to the technical field of wound repair materials. The invention takes a flat silk fiber film as a substrate material, and astaxanthin silk fibroin nanoparticles are loaded on the surface of the flat silk fiber film. The astaxanthin-loaded silk fiber wound repair film provided by the invention has excellent oxidation resistance, excellent biocompatibility, anti-inflammatory performance and wound healing promoting performance, can be used for treating different types of wound management problems such as infectious wound repair and postoperative wound repair, effectively solves the defects of poor anti-inflammatory oxidation resistance and water permeability and air permeability of the traditional dressing, and avoids secondary damage of the dressing to the wound surface. The invention takes the flat silk fiber film as the base material, not only has good biocompatibility, air permeability and water permeability and mechanical property of silk, but also can better control the size, and can design the shape and the size of the silk film which is more attached to the skin according to different requirements.
Description
Technical Field
The invention relates to the technical field of wound repair materials, in particular to an astaxanthin-loaded silk fiber wound repair film, and a preparation method and application thereof.
Background
The skin covers the whole body of the human body, is one of the largest organs of the human body, and is also the first barrier of the human body facing the outside. The skin contains rich blood vessels and neural networks, and can continuously perform metabolism and self-repair. The skin is inevitably damaged to different degrees in daily life, the body of a human body can be defended by small skin wounds, but the metabolism disorder of the body, the unbalance of immunity, the unbalance of electrolyte and the invasion of pathogenic substances can be caused by large skin wounds, and the serious people can shock and die. In order to prevent this, wound repair materials are required to assist in healing of human wounds.
However, conventional wound repair dressings (e.g., inert wound repair dressings are mostly solid, include gypsum, gauze, bandages, and the like) only cover the wound surface to prevent wound infection, have no effect of promoting wound healing, have poor anti-inflammatory and antioxidant properties and water and air permeability, and are easy to secondarily injure the wound surface when used improperly.
The silk is taken as a pure natural protein fiber, contains 18 amino acids necessary for human body, has the advantages of smoothness, softness, skin friendliness, good air permeability, good biocompatibility and the like, is considered as an ideal material for preparing biological materials, and has been applied to the repair of various tissues and organs of the human body such as skin, blood vessels, nerves, bones/cartilages and the like. The existing researches show that leucine and histidine in the silk component are amino acids necessary for healing skin wounds, and the added silk material can be directly absorbed by the skin when being applied to the wounds, so that the healing of the wounds is promoted, bacterial infection is inhibited, and the silk material has a promoting effect on regeneration of skin epidermis tissues such as burns, scalds and the like. In addition, natural moisture controlling factors in the stratum corneum of the skin consist of amino acids, pyrrolidone hydroxy acids, lactate, and the like. The silk polypeptide in silk contains soluble protein, random curled molecular conformation and many polar hydrophilic groups on polypeptide chain, so that the moisture content in skin is moderate, the skin is rich in elasticity, and the skin surface is smooth and soft.
However, pure silk does not have oxidation resistance as a wound repair material, and it is difficult to achieve an effect of promoting rapid healing of a wound surface.
Disclosure of Invention
In view of the above, the present invention aims to provide an astaxanthin-loaded silk fiber wound repair film, and a preparation method and application thereof. The astaxanthin-loaded silk fiber wound repair film provided by the invention has excellent oxidation resistance, anti-inflammatory performance, water permeability and air permeability, and can effectively promote rapid healing of wound surfaces.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a preparation method of a silk fiber wound repair film loaded with astaxanthin, which comprises the following steps:
carrying out hot pressing on the flat silk film to obtain a hot-pressed flat silk fiber film;
placing the hot-pressed flat silk fiber film in a ternary solution, and carrying out surface micro-dissolution treatment to obtain a pretreated flat silk fiber film; the ternary solution comprises CaCl 2 Ethanol and water;
dissolving freeze-dried silk fibroin in water to form a silk fibroin solution, adding astaxanthin to obtain a mixed solution of astaxanthin and silk fibroin, and then dripping the mixed solution into an acetone solution to obtain astaxanthin-loaded silk nanoparticles;
and soaking the pretreated flat silk fiber film in an astaxanthin silk fibroin nanoparticle solution, and carrying out oscillation mixing to enable the astaxanthin silk fibroin nanoparticle and the fiber film to carry out self-assembly, so as to obtain the astaxanthin-loaded silk fiber wound repair film.
Preferably, the thickness of the flat silk film is 0.05-0.5 mm;
the hot pressing temperature is 60-100 ℃, the pressure is 10-20 MPa, and the heat preservation and pressure maintaining time is 3-10 min.
Preferably, before the hot pressing, the method further comprises the step of immersing the flat silk film in water.
Preferably, in the ternary solution, caCl 2 The mol ratio of ethanol to water is 0.9-1:2:6.5-8.
Preferably, the temperature of the surface micro-dissolution treatment is 55-75 ℃ and the time is 5-30 min.
Preferably, the mass ratio of the astaxanthin to the silk fibroin is 0.1-0.2:1.
Preferably, the particle size of the astaxanthin silk nanoparticle is 150-250 nm.
Preferably, the concentration of the astaxanthin silk fibroin nanoparticle solution is 2-6 mg/mL;
the time of the load is 4-36 h.
The invention provides an astaxanthin-loaded silk fiber wound repair film prepared by the preparation method, which comprises a flat silk fiber film and astaxanthin nanoparticles loaded on the surface of the flat silk fiber film.
The invention provides application of the astaxanthin-loaded silk fiber wound repair film in preparation of medical dressing consumables.
The invention provides a preparation method of a silk fiber wound repair film loaded with astaxanthin, which comprises the following steps: carrying out hot pressing on the flat silk film to obtain a hot-pressed flat silk fiber film; soaking the hot-pressed flat silk fiber film in a ternary solution, and performing surface treatment to obtain a pretreated flat silk fiber film; the ternary solution comprises CaCl2, ethanol and water; dissolving freeze-dried silk fibroin in water to form a silk fibroin solution, adding astaxanthin to obtain a mixed solution of astaxanthin and silk fibroin, and then dripping the mixed solution into an acetone solution to obtain astaxanthin-loaded silk nanoparticles (abbreviated as ASTA-SFNPs); and soaking the pretreated flat silk fiber film in an astaxanthin silk fibroin nanoparticle solution, and carrying out oscillation mixing to enable the astaxanthin silk fibroin nanoparticle and the fiber film to carry out self-assembly, so as to obtain the astaxanthin-loaded silk fiber wound repair film. The invention takes the flat silk fiber film as the base material, not only has good biocompatibility, air permeability and water permeability and mechanical property of silk, but also can better control the size, and can design the shape and the size of the silk film which is more attached to the skin according to different requirements.
In the invention, astaxanthin is used as a high-efficiency pure natural antioxidant, has a special molecular structure, can penetrate through the outer wall of human cells, directly eliminates oxygen free radicals in the cells, enhances the regeneration capacity of the cells, maintains the functional balance of the human body and reduces the accumulation of aging cells; the silk fibroin has the characteristics of good biocompatibility, low immunogenicity, processability, degradability, innocuity and harmlessness of degradation products and the like, and has good healing promoting capability. The application uses the flat silk fiber film as a base material, and the astaxanthin silk fibroin nanoparticle is loaded on the surface, so that the astaxanthin-loaded silk fiber wound repair film has excellent oxidation resistance, excellent biocompatibility, anti-inflammatory performance and wound healing promoting performance, can be used for treating wound management problems of different types such as infectious wound repair and postoperative wound repair, effectively solves the defects of poor anti-inflammatory oxidation performance and water permeability and air permeability of the traditional dressing, and avoids secondary damage of the dressing to the wound surface.
Drawings
FIG. 1 is a scanning electron microscope image of a pretreated flat silk fiber film;
FIG. 2 is a graph showing the contact angle of the pretreated flat silk fiber film;
FIG. 3 is a graph showing the particle size distribution of ASTA-SFNPs;
FIG. 4 is a transmission electron microscope image of ASTA-SFNPs;
FIG. 5 is a potential diagram of ASTA-SFNPs;
FIG. 6 is a Fourier infrared spectrum of SFNPs, ASTA, 20% ASTA-SFNPs;
FIG. 7 shows the astaxanthin-carrying rate of astaxanthin-loaded silk fiber wound repair films obtained in examples 1 to 3;
FIG. 8 shows the astaxanthin nanoparticle encapsulation efficiency of the astaxanthin-loaded silk fiber wound repair films obtained in examples 1 to 3;
FIG. 9 shows the results of fluorescence analysis of cell staining experiments;
fig. 10 shows photographs of wounds of animal experiments at 0d, 3d, 7d and 14d post-operation;
FIG. 11 is a graph of wound shrinkage over time;
FIG. 12 is a schematic of the wound healing effect of a commercial dressing, PFSC-C-A6, on a wound.
Detailed Description
The invention provides a preparation method of a silk fiber wound repair film loaded with astaxanthin, which comprises the following steps:
carrying out hot pressing on the flat silk film to obtain a hot-pressed flat silk fiber film;
placing the hot-pressed flat silk fiber film in a ternary solution, and carrying out surface micro-dissolution treatment to obtain a pretreated flat silk fiber film; the ternary solution comprises CaCl 2 Ethanol and water;
dissolving freeze-dried silk fibroin in water to form a silk fibroin solution, adding astaxanthin to obtain a mixed solution of astaxanthin and silk fibroin, and then dripping the mixed solution into an acetone solution to obtain astaxanthin-loaded silk nanoparticles;
and soaking the pretreated flat silk fiber film in an astaxanthin silk fibroin nanoparticle solution, and carrying out oscillation mixing to enable the astaxanthin silk fibroin nanoparticle and the fiber film to carry out self-assembly, so as to obtain the astaxanthin-loaded silk fiber wound repair film.
The flat silk film is subjected to hot pressing, and the hot-pressed flat silk fiber film is obtained. In the present invention, the flat plate silk is preferably a flat plate silk obtained by laying five-year old clustered mature silkworms on a two-dimensional laying bed plane.
In the present invention, the flat wire film is preferably obtained by layering the flat wire. In the present invention, the thickness of the flat wire film is preferably 0.05 to 0.5mm, more preferably 0.1 to 0.4mm, and even more preferably 0.2 to 0.3mm. In the present invention, the mass of the flat wire film is preferably 0.02 to 0.05g, more preferably 0.03 to 0.04g, and the shape is preferably rectangular.
In the invention, the flat silk has good biocompatibility, air permeability and water permeability and mechanical property of silk, can better control the size, and can design the shape and the size of the silk which is more fit with the skin according to different requirements. Compared with the traditional medical dressing and other non-silk base medical materials, the flat silk has a unique cocoon layer structure, and well meets the requirements on water retention and ventilation in wound repair. The silk as natural high molecular protein has excellent biocompatibility, healing promoting capacity and degradability.
The present invention preferably uses a hot press to perform the hot pressing. In the present invention, the temperature of the hot pressing is preferably 60 to 100 ℃, more preferably 70 to 90 ℃; the pressure is preferably 10 to 20MPa, more preferably 15MPa; the holding time is preferably 3 to 10 minutes, more preferably 5 to 8 minutes.
In the invention, before the hot pressing, the invention further comprises the step of immersing the flat silk film in water. In the present invention, the time for immersing in water is preferably 10 minutes. In the present invention, the soaking function is to make the flat wire film more tightly packed.
Placing the hot-pressed flat silk fiber film in a ternary solution, and carrying out surface micro-dissolution treatment to obtain a pretreated flat silk fiber film; the ternary solution comprises CaCl 2 Ethanol and water; in the ternary solution, caCl 2 The molar ratio of ethanol to water is preferably 0.9-1:2:6.5-8, more preferably 1:2:8.
In the present invention, the surface micro-dissolution treatment is preferably performed under water bath heating conditions. In the present invention, the temperature of the surface micro-dissolution treatment is preferably 55 to 75 ℃, more preferably 60 to 70 ℃; the time is 5 to 30 minutes, more preferably 10 to 20 minutes. According to the invention, the surface roughness of the silk fiber film of the hot-pressed flat plate is increased by treating the surface of the material with the ternary solution.
After the surface treatment, the obtained pretreated flat silk fiber film is preferably washed and dried. In the present invention, the washing is preferably pure water washing, and the number of times of the washing is preferably 3. In the present invention, the drying is preferably vacuum drying.
The invention dissolves freeze-dried silk fibroin in water to form silk fibroin solution, and adds astaxanthin to obtain mixed solution of astaxanthin and silk fibroin, and then drops the mixed solution into acetone solution to obtain astaxanthin-loaded silk nanoparticle.
In the present invention, the method for producing silk fibroin preferably comprises the steps of:
and (3) sequentially dissolving, boiling, filtering, centrifuging and dialyzing the cocoon shells to obtain the silk fibroin.
In the present invention, the solvent used for dissolution is preferably a 0.5% sodium carbonate solution; the boiling time is preferably 30min; the rate of centrifugation is preferably 10000rpm; the molecular weight cut-off of the dialysis is preferably 8-14 kDa.
In the present invention, the mass ratio of astaxanthin to silk fibroin is preferably 0.1-0.2:1, more preferably 0.15:1, and the mass ratio of silk fibroin to solvent is preferably 1:100.
In the present invention, the mixing means is preferably stirring mixing by a magnetic stirrer. In the present invention, the mixing time is preferably 5 hours.
After obtaining the astaxanthin-loaded silk fibroin nanoparticle, the present invention also preferably freezes and lyophilizes the obtained astaxanthin-loaded silk nanoparticle. In the present invention, the freezing is preferably performed in a refrigerator at-80 ℃, and the freezing time is preferably 4 to 8 hours. The invention preferably carries out the lyophilization in a lyophilizer.
In the present invention, the particle size of the astaxanthin nanoparticles is preferably 150 to 250nm, more preferably 200nm.
According to the invention, the pretreated flat silk fiber film is soaked in astaxanthin silk fibroin nanoparticle solution, and vibration mixing is carried out, so that astaxanthin silk fibroin nanoparticle and the fiber film are self-assembled, and the astaxanthin-loaded silk fiber wound repair film is obtained. In the present invention, the concentration of the astaxanthin silk nanoparticle solution is 2 to 6mg/mL, more preferably 3 to 5mg/mL.
In the present invention, the rate of the shaking mixing is preferably 50 rpm. In the present invention, the temperature of the self-assembly is preferably room temperature, and the time of the self-assembly is preferably 4 to 36 hours, more preferably 10 to 30 hours.
After the loading, the astaxanthin-loaded silk fiber wound repair film is preferably aired.
The invention provides an astaxanthin-loaded silk fiber wound repair film prepared by the preparation method, which comprises a flat silk fiber film and astaxanthin nanoparticles loaded on the surface of the flat silk fiber film.
In the astaxanthin-loaded silk fiber wound repair film, the astaxanthin nanoparticle loading amount is preferably 10-15 wt%.
The invention provides application of the astaxanthin-loaded silk fiber wound repair film in preparation of medical dressing consumables.
The astaxanthin-loaded silk fiber wound repair film provided by the invention has excellent oxidation resistance, excellent biocompatibility, anti-inflammatory performance and wound healing promoting performance, can be used for treating different types of wound management problems such as infectious wound repair and postoperative wound repair, effectively solves the defects of poor anti-inflammatory oxidation resistance and water permeability and air permeability of the traditional dressing, and avoids secondary damage of the dressing to the wound surface.
The astaxanthin-loaded silk fiber wound repair film, the preparation method and application thereof provided by the invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the invention.
Example 1
(1) Selecting 50 mature silkworms with the age of 5, uniformly placing the mature silkworms on a spinning plate, cleaning the mature silkworms on a flat plate after 2-3 days, and stripping flat plate silkworms from the spinning plate.
Taking silkworm plate cocoon samples with the sizes of 5cm and 5cm, immersing the silkworm plate cocoon samples in water, and then placing the silkworm plate cocoon samples into a hot press for thermoplastic molding, wherein the temperature and the pressure time of the hot press are respectively set at 100 ℃, 15MPa and 5min. After autoclave, a ternary solution (CaCl) was prepared at 55 ℃ 2 Ethanol andthe molar ratio of water is 1:2:8) is treated for 10min, and the surface of the flat silk is subjected to micro-dissolution to obtain the pretreated flat silk fiber film.
(2) Preparation of astaxanthin silk nanoparticle
Taking clean cocoon shell, dissolving, boiling, filtering, centrifuging, and dialyzing to obtain silk fibroin. Respectively taking 50mL of acetone in a beaker, respectively adding 10mg/mL, 15 mg/mL and 20 mg/mL of astaxanthin (ASTA) and 10mL of the silk fibroin solution prepared in the steps to prepare 10%, 15% and 20% of astaxanthin silk fibroin nanoparticles (ASTA-SFNPs) and preparing the astaxanthin silk fibroin nanoparticles (ASTA-SFNPs); meanwhile, silk fibroin blank nanoparticles (SFNPs) containing no astaxanthin were prepared.
After ultrasonic treatment for 3min, the ASTA-SFNPs and SFNPs with the concentrations prepared by the steps are placed in a refrigerator for freezing at the temperature of minus 80 ℃ for 6h, and then are rapidly placed in a freeze dryer for freeze drying treatment.
(3) Preparation of astaxanthin-loaded silk mask
And (3) placing the 5cm multiplied by 5cm pretreated flat silk fiber film into astaxanthin nanoparticle solution with the concentration of 2mg/mL, soaking for 36 hours, and obtaining the astaxanthin-loaded silk fiber wound repair film, which is marked as PFSC-C-A2.
Example 2
Compared with example 1, the difference is that the silk fiber wound repair film loaded with astaxanthin is obtained by soaking the silk fiber wound repair film in astaxanthin nanoparticle solution with the concentration of 4mg/mL for 36 hours and is marked as PFSC-C-A4.
Example 3
Compared with example 1, the difference is that the silk fiber wound repair film loaded with astaxanthin is obtained by soaking the silk fiber wound repair film in astaxanthin nanoparticle solution with the concentration of 6mg/mL for 36 hours and is marked as PFSC-C-A6.
The process conditions for the different examples are shown in table 1.
TABLE 1 treatment conditions for the different examples
Comparative example 1
A pretreated flat silk fiber film without astaxanthin nanoparticles was used as comparative example 1.
Structural characterization
The scanning electron microscope image of the astaxanthin-loaded silk fiber wound repair film is shown in figure 1, 1-15 are PFSC-55-5 respectively (55 in PFSC-55-5 means the temperature of the surface micro-dissolution treatment is 55 ℃, and 5 means the time is 5 min); PFSC-55-10; PFSC-55-15; PFSC-55-20; PFSC-55-30; PFSC-60-10; PFSC-60-15; PFSC-60-20; PFSC-60-30; PFSC-65-5; PFSC-65-15; PFSC-65-20; PFSC-70-5; PFSC-70-10; PFSC-75-5. As can be seen from FIG. 1, the treatment effect of treating the flat filaments with the ternary solution at 55 ℃ for 10min is optimal.
The contact angle of astaxanthin-loaded silk fiber wound repair film is shown in fig. 2. As can be seen from FIG. 2, the contact angle effect is best when the flat wire is treated by the ternary solution at 55 ℃ for 10min.
The particle size distribution of astaxanthin nanoparticles is shown in FIG. 3. In FIG. 3, 1 to 4 are SFNPs, respectively; 10% ASTA-SFNPs;15% ASTA-SFNPs;20% ASTA-SFNPs. As can be seen from FIG. 3, the ASTA-SFNPs were successfully prepared by the acetone volatilization method, and the particle size was concentrated at about 200nm.
A transmission electron microscope image of the astaxanthin nanoparticles is shown in FIG. 4. From left to right in fig. 4 are respectively astm a, SFNPs, 20% astm a-SFNPs. As can be seen from fig. 4, the silk fibroin nanoparticles and astaxanthin-loaded silk fibroin nanoparticles present spherical particles with smooth surfaces and uniform sizes. Bulk crystals of astaxanthin are not present in the drug-loaded silk fibroin. It was shown that astaxanthin is well entrapped in silk fibroin.
The potential diagram of astaxanthin nanoparticles is shown in FIG. 5. As can be seen from FIG. 5, the Zeta potential of the astaxanthin silk fibroin nanoparticle prepared with the astaxanthin concentration of 2mg/mL is-29.942 +/-0.756 mV, and the absolute value is more than 20mV, which indicates that the silk fibroin nanoparticle dispersion system prepared with the astaxanthin with the concentration is relatively stable.
SFNPs, ASTA, 20% ASTA-SFNPs Fourier infrared spectra are shown in FIG. 6. As can be seen from fig. 6, in the astaxanthin-loaded silk protein nanoparticle, all absorption peaks of the silk nanoparticle can be found, and the spectra of the astaxanthin and the astaxanthin-loaded silk protein nanoparticle are compared, so that the specific absorption peak of the astaxanthin appears in the astaxanthin-loaded silk nanoparticle, and the position of the characteristic absorption peak is unchanged. It is indicated that astaxanthin is successfully encapsulated in the silk fibroin, and the pharmacodynamic performance of astaxanthin is not changed by the silk fibroin.
The astaxanthin-loaded silk fiber wound repair films obtained in examples 1 to 3 have astaxanthin nanoparticle drug loading rates shown in FIG. 7 and encapsulation rates shown in FIG. 8. As can be seen from fig. 7 and 8, the astaxanthin silk nanoparticle prepared when the astaxanthin concentration is 2mg/mL has the highest drug loading and encapsulation efficiency, which indicates that the astaxanthin silk nanoparticle prepared under the concentration condition has better embedding effect.
Test example 1 cell staining experiment
The experimental steps are as follows: 1. matrigel (artificial basement membrane gel) was prepared to 0.04. Mu.g/. Mu.L of artificial basement membrane gel using serum-free medium RPMI-1640, 2. Mu.g Matrigel was plated per well of 96 well plates and allowed to air dry overnight in an ultra clean bench.
2. Adding a proper amount of serum-free RPMI-1640 cell culture solution (or PBS or physiological saline) into a 96-well plate, and standing for 60-90 min.
3. Washing off excessive gum, collecting cultured tumor cells at a ratio of 1×10 4 The wells were inoculated in a gel-plated 96-well plate, 3 replicate wells were placed in a 37℃5% CO2 incubator for 24h.
4. PFSC-C, PFSC-C-A2, PFSC-C-A4 and PFSC-C-A6 were added respectively to culture for 48 hours.
5. The dye was added, and the Live/read working solution was prepared in a dark condition at a ratio of 2mL of LPBS solution+4. Mu.L of C-AM+6. Mu.L of PI.
Pbs solution wash: 96-well plates were plated out of the medium and washed twice with PBS.
7. Cell staining: adding a staining agent, adding 300 mu L of the staining agent into each well of a 96-well plate, incubating for 20min at 37 ℃, washing the excessive staining agent by using PBS, and adding a proper amount of culture solution.
8. Fluorescence analysis: the results were examined with a fluorescence microscope. The maximum excitation of the dye-DNA complex is 490nm.
The results of the fluorescent analysis of the cell staining experiments are shown in FIG. 9. As can be seen in FIG. 9, the number of living cells was the greatest and the number of dead cells was the least for PFSC-C-A4, indicating that PFSC-C-A4 cytotoxicity was the least.
Test example 2 animal experiment
The experimental steps are as follows: after 1d of depilation, the mice were anesthetized with diethyl ether and fixed to the rat plates with the limbs lying down after complete anesthesia. After shaving the back of the animal, the animal is smeared with depilatory cream, the animal is scraped after the animal is left for 2 to 3 minutes, the residual depilatory cream is scraped by warm water, the residual moisture on the surface of the skin is wiped off by soft absorbent paper, and then the animal is vertically pressed on the skin by a sterile skin trephine (phi 16 mm) and rotated by proper force until penetrating through the whole layer of the skin, and the skin is sheared by surgical scissors to form a wound surface. The rat full-thickness skin wound model is used for evaluating the influence of the silk fibroin nanofiber membrane dressing before and after astaxanthin nanoparticle modification on the wound healing effect. Animal experiments were carried out in 5 groups, namely a silk fibroin nanofiber group (PSFC-C), astaxanthin silk nanofiber groups with different concentrations (PSFC-C-A2 and PFSC-C-A6), a commercial dressing control group (3M) and a gauze blank group. After the operation is finished, two mice treated in the same way are fed in each cage, and the wound infection condition, the state of the mice, the wound healing condition, the skin damage applying condition and the like of the mice are observed in 3d, 7d and 14d respectively. And 3 mice were sacrificed at 7d and 14d, respectively, for pathological section examination.
The results of the animal experiments are shown in fig. 10, 11 and 12. Fig. 10 shows photographs of wounds of each group after operation of 0d, 3d, 7d and 14d, fig. 11 is a graph showing the change of the shrinkage rate of the wound with time, and fig. 12 is a schematic view showing the wound healing effect of the commercial dressing, PFSC-C-A6, on the wound.
In the 3d post-operation, astaxanthin silk fibroin nanofiber groups, the wound surface is still covered with an weight, and the wound area is reduced to a certain extent compared with the other two groups; in the 7d after operation, the wound starts to heal from the edge to the center, the crusting phenomenon occurs, and the wound area of the astaxanthin silk nanofiber membrane group is the smallest; at the 14d th stage after operation, all the scabs are fallen off, the wound center area is further reduced, the wound edge of the astaxanthin silk nanofiber membrane group is greatly reduced, and the surface is the smoothest and is close to the whole skin. It can be seen that at each observation time point after surgery, the PFSC-C-A2, PFSC-C-A6 groups all exhibited better wound contraction tendencies than the commercial dressing groups (FIGS. 10, 11). On day 3, the wound areas of both groups were reduced, but the wound surface of the experimental group was more significantly reduced, reaching a shrinkage of 31%. Fig. 12 is a schematic view of wound healing effect of two groups of treated wounds, which intuitively shows that the healing promoting effect of the materials of the experimental group is better than that of the commercial dressing group.
From this, astaxanthin silk nanofiber membrane dressing can promote wound healing, and repair effect is better than commercial dressing.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. A preparation method of astaxanthin-loaded silk fiber wound repair film comprises the following steps:
carrying out hot pressing on the flat silk film to obtain a hot-pressed flat silk fiber film;
placing the hot-pressed flat silk fiber film in a ternary solution, and carrying out surface micro-dissolution treatment to obtain a pretreated flat silk fiber film; the ternary solution comprises CaCl 2 Ethanol and water;
dissolving freeze-dried silk fibroin in water to form a silk fibroin solution, adding astaxanthin to obtain a mixed solution of astaxanthin and silk fibroin, and then dripping the mixed solution into an acetone solution to obtain astaxanthin-loaded silk nanoparticles;
and soaking the pretreated flat silk fiber film in an astaxanthin silk fibroin nanoparticle solution, and carrying out oscillation mixing to enable the astaxanthin silk fibroin nanoparticle and the fiber film to carry out self-assembly, so as to obtain the astaxanthin-loaded silk fiber wound repair film.
2. The method according to claim 1, wherein the thickness of the flat wire film is 0.05 to 0.5mm;
the hot pressing temperature is 60-100 ℃, the pressure is 10-20 MPa, and the heat preservation and pressure maintaining time is 3-10 min.
3. The method of claim 1, further comprising immersing the flat wire film in water prior to the hot pressing.
4. The method of claim 1, wherein CaCl is present in the ternary solution 2 The mol ratio of ethanol to water is 0.9-1:2:6.5-8.
5. The method according to claim 1 or 4, wherein the surface micro-dissolution treatment is carried out at a temperature of 55 to 75 ℃ for a time of 5 to 30 minutes.
6. The method according to claim 1, wherein the mass ratio of astaxanthin to silk fibroin is 0.1-0.2:1.
7. The method according to claim 1, wherein the astaxanthin nanoparticles have a particle diameter of 150 to 250nm.
8. The method of claim 1, wherein the concentration of the astaxanthin nanoparticle solution is 2-6 mg/mL;
the time of the load is 4-36 h.
9. The astaxanthin-loaded silk fiber wound repair film prepared by the preparation method according to any one of claims 1 to 8, which comprises a flat silk fiber film and astaxanthin nanoparticles loaded on the surface of the flat silk fiber film.
10. Use of the astaxanthin-loaded silk fiber wound repair film of claim 9 in the preparation of medical dressing consumables.
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