Core-shell structure nanofiber, core-shell structure nanofiber membrane and preparation method thereof

Abstract

The present application belongs to the technical field of core-shell structure fiber, and discloses a core-shell structure nanofiber, a core-shell structure nanofiber membrane and a preparation method thereof. The shell layer of the core-shell structure nanofiber comprises cellulose acetate as a base material and sodium carboxymethyl cellulose embedded in the form of discrete hydrophilic sites. The core layer comprises polypropylene carbonate as a base material and silver sulfadiazine coated therein. The mass of sodium carboxymethyl cellulose in the shell layer is 1.2% to 2.0% of the mass of cellulose acetate. The preparation method of the fiber membrane composed of the core-shell structure nanofiber is as follows: coaxial electrospinning of the shell layer spinning solution and the core layer spinning solution to obtain the core-shell structure nanofiber membrane. The solvents in the shell layer spinning solution and the core layer spinning solution are both mixtures of acetone and DMAC at a volume ratio of 2:1. The present application can match the healing time sequence of the wound, and has the functions of initial hydrophobic anti-adhesion barrier, rapid hydrophilic liquid absorption and 14-day stable drug release.

Description

Technical Field

[0001] This invention belongs to the field of core-shell structured fiber technology, and relates to a core-shell structured nanofiber, a core-shell structured nanofiber membrane, and a method for preparing the same. Background Technology

[0002] Infected wound repair presents a significant clinical challenge. Traditional dressings have significant limitations in maintaining a moist wound environment, controlling infection, and promoting tissue regeneration. Electrospinning technology can fabricate three-dimensional fibrous scaffolds that mimic the topology of the extracellular matrix (ECM), providing an ideal template for cell adhesion and growth, and possessing the potential to load active ingredients. However, traditional uniaxial electrospun drug-loaded fibers often face the problem of drug burst release, leading to increased early cytotoxicity and insufficient antibacterial efficacy in the later stages.

[0003] Silver sulfadiazine (SS) is a widely used broad-spectrum antibacterial agent in clinical practice. Existing silver sulfadiazine nanofibers commonly exhibit burst release: rapid release typically occurs within hours (10-24 hours), with complete release occurring within 1-2 weeks. This is a common problem with nanofiber materials due to their short diffusion pathways. This release behavior easily leads to pseudoeschar formation and cytotoxicity, while also increasing the frequency of silver sulfadiazine administration and exposure time.

[0004] Core-shell structured fibers encapsulate drugs in an inner layer (core) and utilize the outer layer (shell) as a diffusion barrier, enabling controlled and prolonged drug release, thus addressing the aforementioned burst release problem to some extent. For example, the literature (Potential of novel electrospun core-shell structured polyurethane / starch (hyaluronicacid) nanofibers for skin tissue engineering: In vitro and in vivo evaluation[J]. International Journal of Biological Macromolecules, 2020, 146, 627-637.) discloses an electrospun core-shell structured polyurethane / starch-hyaluronic acid nanofiber, which uses polyurethane / starch as the core and hyaluronic acid as the shell. The hydrophilicity of the shell regulates the drug release rate, thus delaying drug release to some extent compared to uniaxial fibers.

[0005] However, conventional core-shell drug-loaded fibers rely solely on shell thickness and / or material to regulate the release rate, failing to simultaneously achieve the sequential function of "initial hydrophobic barrier → rapid hydrophilic absorption in 5-10 minutes → stable sustained release over 14 days." Specifically: if the shell uses a continuously hydrophilic material, the dressing absorbs fluid immediately upon contact with the wound, easily adhering to newly formed granulation tissue during dressing changes, causing secondary mechanical damage, increasing patient suffering, and delaying the healing process; if the shell uses a continuously hydrophobic material, it cannot absorb wound exudate in time during the inflammatory phase, making it difficult to form a moist healing microenvironment, which is detrimental to cell migration and proliferation; moreover, the single release mode cannot match the dynamic sequence of wound healing—wound healing sequentially goes through the hemostasis phase (0-24 hours, requiring a hydrophobic barrier to prevent external bacterial invasion), the inflammatory phase (1-3 days, requiring rapid fluid absorption to drain exudate and continuous antibacterial action), and the proliferative phase (3-14 days, requiring stable sustained antibacterial release to support tissue regeneration). Conventional core-shell fibers cannot provide differentiated interfacial properties and drug release behavior at different stages.

[0006] Therefore, it is necessary to design a core-shell nanofiber that matches the wound healing timeline and has multiple temporal functions, including an initial hydrophobic anti-adhesion barrier (hemostasis phase), rapid hydrophilic fluid absorption (inflammatory phase), and stable sustained drug release over 14 days (proliferative phase), as well as its preparation method. Summary of the Invention

[0007] The purpose of this invention is to solve the problems existing in the prior art and to provide a core-shell structured nanofiber, a core-shell structured nanofiber membrane, and a method for preparing the same.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] A core-shell structured nanofiber, wherein the shell comprises cellulose acetate (CA) as a substrate and sodium carboxymethyl cellulose (CMC) embedded therein in the form of discrete hydrophilic sites, and the core comprises polypropylene carbonate (PPC) as a substrate and a drug, namely silver sulfadiazine, encapsulated therein; the mass of sodium carboxymethyl cellulose in the shell is 1.2% to 2.0% of the mass of cellulose acetate.

[0010] The fiber of the present invention has a complete core-shell topology formed by coaxial electrospinning. Sodium carboxymethyl cellulose is embedded in hydrophobic cellulose acetate in the form of discrete hydrophilic sites. Due to the constraint of the dense aggregated structure of the fiber, the hydrophilic groups of sodium carboxymethyl cellulose are initially difficult to be fully exposed on the fiber surface, so that the shell layer only retains the intrinsic hydrophobicity of cellulose acetate. When applied to the wound during the hemostasis period, it can form a hydrophobic physical barrier, thereby achieving the functions of anti-adhesion, preventing secondary damage to the wound and isolating exogenous bacteria.

[0011] When the fiber comes into contact with wound fluid or exudate for 5 to 10 minutes, water molecules gradually penetrate into the fiber and induce the hydrophilic groups of sodium carboxymethyl cellulose to hydrate, stretch, and migrate to the fiber interface, so that the fiber dynamically changes from an initial hydrophobic state to a hydrophilic state and autonomously and completely absorbs the wound exudate, which meets the needs of rapid fluid absorption and maintaining a moist healing microenvironment during the inflammatory phase of the wound.

[0012] The drug is encapsulated in hydrophobic polypropylene carbonate in the core layer. Wound fluid or exudate slowly permeates into the core layer through the hydrophilic channels formed by sodium carboxymethyl cellulose in the shell layer. The drug gradually dissolves and is released outward at a limited rate through the dual diffusion barriers of polypropylene carbonate and shell layer. While ensuring rapid initial antibacterial effect, it inhibits drug burst release and cytotoxicity caused by excessive silver ions, forming a stable sustained-release kinetic. The effective sustained-release period of the drug can reach 14 days, which is suitable for the long-term antibacterial effect during the proliferative phase of wounds and the use of the drug to protect the sequential repair of tissues.

[0013] Based on the core-shell structure, this invention introduces hydrophilic sodium carboxymethyl cellulose into the shell layer to form individual drug delivery channels. The number of hydrophilic points determines the drug release rate, so controlling the content of sodium carboxymethyl cellulose in the shell layer can control the drug release rate.

[0014] Both the shell substrate and the core substrate of this invention are biodegradable materials, which can reduce the environmental pollution of current medical dressings.

[0015] As a preferred technical solution:

[0016] The core-shell structured nanofiber described above has a diameter of 575~1035.2 nm and a core layer diameter of 164~195 nm.

[0017] The core-shell structured nanofiber described above has a drug mass in the core layer that is 5% to 10% of the mass of polypropylene carbonate.

[0018] The core-shell structured nanofiber described above has a cellulose acetate weight-average molecular weight of 7.27 × 10⁻⁶. 4 g·mol -1 The molecular weight distribution index is 1.67; the weight-average molecular weight of sodium carboxymethyl cellulose is 9.0 × 10⁻⁶. 4 g·mol -1 The molecular weight distribution index is 1.01; the weight-average molecular weight of polypropylene carbonate is 6.9 × 10⁻⁶. 4 g·mol -1 The molecular weight distribution index is 1.20.

[0019] The present invention also provides a core-shell structured nanofiber membrane, which is composed of a core-shell structured nanofiber as described above.

[0020] As a preferred technical solution:

[0021] The core-shell structured nanofiber membrane described above has a thickness of 0.52~0.38 mm and a specific surface area of ​​58.49~84.65 m². 2 / g;

[0022] The initial water contact angle of the core-shell structured nanofiber membrane is 115~127.9°, the time taken to reach a 90° water contact angle is 181~566s, the time taken to reach a 45° water contact angle is 8~206s, and the time taken to reach a 0° water contact angle is 11~127s.

[0023] After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 28.9%–42.6% after 1 hour, 51.5%–68.3% after 2 hours, 69.8%–79.7% after 1 day, and 78.3%–89.9% after 2 days. It took 14 days to reach a 100% cumulative drug release rate.

[0024] The core-shell structured nanofiber membrane exhibits a 24-hour inhibition rate of ≥99.98% against Gram-positive bacteria and ≥99.99% against Gram-negative bacteria.

[0025] The present invention also provides a method for preparing a core-shell structured nanofiber membrane as described above, wherein the shell spinning solution and the core spinning solution are coaxially electrospun to obtain the core-shell structured nanofiber membrane; the solvents in the shell spinning solution and the core spinning solution are both a mixture of acetone and DMAC (N,N-dimethylacetamide) in a volume ratio of 2:1; the viscosity of the shell spinning solution is 365~383 mPa·s, and the viscosity of the core spinning solution is 263~271 mPa·s.

[0026] The biggest challenge in coaxial electrospinning is the incompatibility of core / shell solvents, leading to easy phase separation or failure to form fibers. Existing technologies have not found a universally suitable solvent for cellulose acetate and polypropylene carbonate. Commonly used cellulose acetate and polypropylene carbonate solvents react, preventing fiber formation. Therefore, those skilled in the art generally believe that cellulose acetate and polypropylene carbonate are difficult to coaxially electrospin. This invention unexpectedly discovered that a mixture of acetone and DMAC in a specific volume ratio can serve as a universally suitable solvent for cellulose acetate and polypropylene carbonate, successfully enabling coaxial electrospinning and yielding a continuous, bead-free, core-shell intact fiber structure. Furthermore, the mechanical properties and film-forming properties of the fiber membrane meet dressing requirements.

[0027] As a preferred technical solution:

[0028] As described above, the process parameters for coaxial electrospinning include: shell solution flow rate 0.04~0.06 mm / min, core solution flow rate 0.12~0.20 mm / min, forward voltage 28~30 kV, reverse voltage -2~-4 kV, receiving distance 10~15 cm, receiving rotation speed 60~100 rpm, ambient temperature 28±2°C, and ambient relative humidity 55±10%.

[0029] Beneficial effects:

[0030] (1) Existing core-shell drug-loaded fibers rely solely on shell thickness and / or material to regulate the release rate, which cannot simultaneously achieve the sequential function of "initial hydrophobic barrier → rapid hydrophilic absorption in 5~10 min → stable sustained release in 14 days". However, this invention, through the design of the shell and core components, makes the shell retain only the intrinsic hydrophobicity of cellulose acetate. Only when water molecules gradually penetrate into the fiber will the fiber dynamically change from the initial hydrophobic state to the hydrophilic state and autonomously and completely absorb the wound exudate. As the formed hydrophilic channel slowly penetrates into the core layer, the drug begins to gradually dissolve and be released outward. This design allows the core-shell structure nanofiber membrane of this invention to match the wound healing sequence and has multiple sequential functions, including initial hydrophobic anti-adhesion barrier, rapid hydrophilic absorption, and stable sustained release of drugs in 14 days.

[0031] (2) Existing silver nanofibers loaded with sulfadiazine generally exhibit drug burst release. However, this invention encapsulates the drug within a hydrophobic polypropylene carbonate core. Only after wound fluid or exudate slowly permeates into the core through the hydrophilic channels formed by sodium carboxymethyl cellulose in the shell will the drug gradually dissolve and be released outward at a rate limited by the double diffusion barrier of polypropylene carbonate and shell, thus avoiding burst release. Furthermore, based on the core-shell structure, this invention introduces hydrophilic sodium carboxymethyl cellulose into the shell to form individual drug delivery channels. The number of hydrophilic points determines the drug release rate, so controlling the content of sodium carboxymethyl cellulose in the shell can control the drug release rate.

[0032] (3) In the preparation of core-shell structured nanofiber membranes, the commonly used cellulose acetate solvent and the commonly used polypropylene carbonate solvent react and cannot form fibers. However, the present invention uses a mixture of acetone and DMAC in a specific volume ratio as a universal good solvent for cellulose acetate and polypropylene carbonate, and successfully performs coaxial electrospinning to obtain a continuous, beadless, core-shell complete fiber structure. The mechanical properties and film-forming properties of the fiber membrane meet the requirements of dressings. Attached Figure Description

[0033] Figure 1 This is a schematic diagram of the internal structure of the core-shell nanofibers of the present invention;

[0034] Figure 2 This is a SEM image of the core-shell structured nanofiber membrane prepared in Example 3 of the present invention;

[0035] Figure 3 This is a TEM image of the core-shell structured nanofibers prepared in Example 3 of the present invention;

[0036] Figure 4 The infrared spectrum of the core-shell structured nanofiber membrane prepared in Example 3 of this invention;

[0037] Figure 5 This diagram illustrates the cumulative drug release rate of the fiber membranes prepared in Examples 1-3 and Comparative Example 3 of this invention. The cumulative release rate exceeding 100% is because during the testing process, the medical dressing matrix, including cellulose acetate and sodium carboxymethyl cellulose, dissolved polysaccharides, peptides, and small molecule degradation fragments after immersion and degradation in the release medium (PBS). These degradation products exhibit characteristic ultraviolet absorption at the drug detection wavelength. When measuring absorbance spectrophotometry, the matrix absorption and drug absorption are superimposed, resulting in a higher measured total absorbance and a higher calculated drug concentration, thus causing the cumulative drug release rate to exceed 100%.

[0038] Figure 6 The figures show the antibacterial results of the fibrous membranes prepared in Examples 1-3 and Comparative Example 3 against Escherichia coli. In the figures, I is the control group against Escherichia coli, a is the antibacterial result of the fibrous membrane in Example 1 against Escherichia coli, b is the antibacterial result of the fibrous membrane in Example 2 against Escherichia coli, c is the antibacterial result of the fibrous membrane in Example 3 against Escherichia coli, and d is the antibacterial result of the fibrous membrane in Comparative Example 3 against Escherichia coli.

[0039] Figure 7 The figures show the antibacterial results of the fibrous membranes prepared in Examples 1-3 and Comparative Example 3 against Staphylococcus aureus. In the figures, II is the control group against Staphylococcus aureus, a is the antibacterial result of the fibrous membrane in Example 1 against Escherichia coli, b is the antibacterial result of the fibrous membrane in Example 2 against Escherichia coli, c is the antibacterial result of the fibrous membrane in Example 3 against Escherichia coli, and d is the antibacterial result of the fibrous membrane in Comparative Example 3 against Escherichia coli.

[0040] Figure 8 This is a SEM image of the composite fiber membrane prepared in Comparative Example 1 of the present invention.

[0041] Figure 9 The images show SEM and TEM images of the composite fiber membrane prepared in Comparative Example 4 of this invention; in the images, a is the SEM image of the composite fiber membrane and b is the TEM image of the composite fiber membrane.

[0042] Figure 10 This is a SEM image of the composite fiber membrane prepared in Comparative Example 5 of the present invention;

[0043] In the diagram, 1 represents the shell, 2 the core, 3 the sodium carboxymethyl cellulose, and 4 the silver sulfadiazine. Detailed Implementation

[0044] The present invention will be further described below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Furthermore, it should be understood that after reading the teachings of this invention, those skilled in the art can make various alterations or modifications to the invention, and these equivalent forms also fall within the scope defined by the appended claims.

[0045] The manufacturers and brands mentioned in the following embodiments are merely examples. The core of this invention lies in the technical solution itself, and it is not intended to limit specific manufacturers or brands. Products from other manufacturers and brands that meet the technical requirements and performance indicators specified in this invention can also meet the application requirements of this invention and are all feasible choices.

[0046] The test methods for the relevant performance indicators in the following embodiments and comparative examples are as follows:

[0047] Water contact angle testing and the time required to reach 90°, 45°, and 0°: The static water contact angle of the sample was measured using a video optical contact angle meter (KRȔSS DSA30, Germany) to evaluate its hydrophilicity / hydrophobicity. The initial contact angle size and the time required to reach 90°, 45°, and 0° were determined by dynamic video. The same sample was tested 5 times, and the average value and standard deviation were calculated. In the following examples and comparative examples, A ± B values ​​represent the average value and B the standard deviation.

[0048] Drug release behavior: Accurately weigh 10 mg of the sample and place it in a dialysis bag (MWCO=3500), immerse it in 20 mL of PBS buffer (pH=7.4), and incubate at 37°C with constant shaking (100 rpm). Take 3 mL samples at predetermined time points (i.e., at 1 h, 2 h, 1 day, and 2 days of incubation), and add an equal volume of fresh PBS buffer. Then, use a UV-Vis spectrophotometer (Hitachi 3900H, Japan) to determine the concentration of silver sulfadiazine at a wavelength of 265 nm, and calculate the drug release amount and cumulative drug release amount at a certain time point based on the measured data.

[0049] 24-hour inhibition rate against Staphylococcus aureus and Escherichia coli: Referring to GB / T20944.3-2008 "Evaluation of Antimicrobial Properties of Textiles Part 3: Shaking Method", the 24-hour inhibition rate of the sample against Staphylococcus aureus and Escherichia coli was evaluated using a quantitative method. The test procedure was as follows: The sample (1×1cm) was... 2 ) respectively with 1 mL of a concentration of 1×10 2After co-culturing CFU / mL bacterial suspension I (Staphylococcus aureus ATCC 6538) and bacterial suspension II (Escherichia coli ATCC 8739) for 24 h, the inhibition rate (R) was calculated by plate counting method: R = (A - B) / A × 100%, where A is the average colony count of the blank control group of bacterial suspension and B is the average colony count of the experimental group.

[0050] Viscosity: Tested using a rotational viscometer (Brookfield DV3T, USA) with the following parameters: test speed 50 rpm, torque 37%, and temperature 25℃.

[0051] Diameter of core-shell nanofibers: obtained from SEM statistics.

[0052] The diameter of the core layer: obtained from TEM statistics.

[0053] Example 1

[0054] A method for preparing a core-shell structured nanofiber membrane, comprising the following steps:

[0055] (1) Prepare the shell spinning solution;

[0056] First, cellulose acetate (weight-average molecular weight 7.27 × 10⁻⁶) is... 4 g·mol -1 A homogeneous, transparent solution with a concentration of 15% (w / w) was prepared using sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) and solvent A. Sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) was then added to the solution. 4 g·mol -1 The solution was magnetically stirred until completely dissolved, and allowed to stand for 24 hours to obtain a shell spinning solution with a viscosity of 370 mPa·s. Solvent A was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of sodium carboxymethyl cellulose was 1.5% of the mass of cellulose acetate.

[0057] (2) Prepare the core spinning solution;

[0058] First, polypropylene carbonate (weight average molecular weight 6.9 × 10⁻⁶) is used. 4 g·mol -1 A spinning solution with a molecular weight distribution index of 1.20 and solvent B was prepared to a concentration of 10% (w / w). Then, silver sulfadiazine was added, and the solution was ultrasonically treated for 30 min to ensure uniform dispersion of the silver sulfadiazine, resulting in a core spinning solution with a stable viscosity of 263 mPa·s. Solvent B was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of silver sulfadiazine was 5% of the mass of polypropylene carbonate.

[0059] (3) The shell spinning solution and the core spinning solution are coaxially electrospun to obtain a fiber membrane. The fiber membrane is then placed in a vacuum oven and dried for 48 hours to remove the solvent in the sample, thus obtaining a core-shell structured nanofiber membrane. The inner needle (23G specification) is used to deliver the core solution, and the outer needle (18G specification) is used to deliver the shell solution.

[0060] The process parameters for coaxial electrospinning include: shell solution flow rate 0.04 mm / min, core solution flow rate 0.12 mm / min, forward voltage 28 kV, reverse voltage -4 kV, receiving distance 10 cm, receiving speed 60 rpm, ambient temperature 28°C, and ambient relative humidity 55%.

[0061] The final core-shell structured nanofiber membrane (its SEM image is shown below) Figure 2 As shown in the figure, the nanofibers in the fiber membrane all exhibit a smooth, continuous, and bead-free morphology, with a uniform fiber diameter distribution, and are composed of core-shell structured nanofibers.

[0062] Infrared spectroscopy was performed on the core-shell nanofiber membrane, and the results are as follows: Figure 4 As shown in the figure, the core-shell nanofiber membrane mainly displays the characteristic peaks of cellulose acetate, with no new characteristic peaks generated or the original characteristic peaks disappearing, proving that the system is mainly based on physical recombination and interfacial interaction, and no obvious chemical reaction has occurred.

[0063] like Figure 1 As shown, the shell 1 of the core-shell structured nanofiber is composed of cellulose acetate as a substrate and sodium carboxymethyl cellulose 3 embedded therein in the form of discrete hydrophilic sites, and the core 2 is composed of polypropylene carbonate as a substrate and silver sulfadiazine 4 coated therein.

[0064] The core-shell nanofibers have a diameter of 694±98 nm and a core diameter of 175±11 nm. A TEM image of one core-shell nanofiber is shown below. Figure 3 As shown in the figure, it can be clearly confirmed that the core-shell nanofibers have a complete core-shell structure, in which the dark core layer is uniformly wrapped by the light shell layer.

[0065] With Figure 2 Compared to the SEM image shown, Figure 3 The TEM image shows that the fiber diameter is relatively thin. This is because, during transmission electron microscopy, the cellulose acetate molecular chains in the composite fiber shell have weak heat irradiation resistance. High-energy electron beams can easily cause main chain breakage, side group removal, and local thermal softening. At the same time, the shell is thin and has low heat capacity, so energy cannot be effectively dissipated, causing chain shrinkage, fragmentation, and volatilization of small molecules in the irradiated area, ultimately resulting in a significant reduction in thickness.

[0066] The core-shell structured nanofiber membrane has a thickness of 0.44 mm and a specific surface area of ​​62.51 m². 2 / g;

[0067] The initial water contact angle of the core-shell structured nanofiber membrane was 122.6±2.3°. It took 331±30s to reach a 90° water contact angle from the initial water contact angle, 189±17s to reach a 45° water contact angle from the 90° water contact angle, and 112±15s to reach a 0° water contact angle (i.e., complete absorption) from the 45° water contact angle.

[0068] After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 34.3% after 1 hour, 64.4% after 2 hours, 75.0% after 1 day, and 81.2% after 2 days. It took 14 days to reach a 100% cumulative drug release rate.

[0069] The core-shell structured nanofiber membrane exhibited a 24-hour inhibition rate of 99.99% against Gram-positive bacteria and 99.99% against Gram-negative bacteria.

[0070] Comparative Example 1

[0071] A method for preparing a fiber membrane is basically the same as in Example 1, except that: in steps (1) and (2), solvent A and solvent B are both a mixture of acetone and DMAC in a volume ratio of 1:1.

[0072] The viscosity of the obtained shell spinning solution was 389 mPa·s, and the viscosity of the core spinning solution was 274 mPa·s.

[0073] The final fiber membrane is composed of non-nanoscale fibers with a flat morphology, as shown in the SEM image. Figure 8 As shown, the fibers are largely stuck together and fail to form a uniform fiber morphology;

[0074] The fiber membrane has a thickness of 0.38 μm. Fiber adhesion leads to a significant reduction in specific surface area, which is 18.24 m². 2 / g.

[0075] After being soaked in PBS buffer at pH 7.4, the cumulative drug release rate of the core-shell fibrous membrane was 10.5% after 1 hour, 16.8% after 2 hours, 24.7% after 1 day, 30.2% after 2 days, and 56.3% by the 14th day of the experiment. The closed area resulted in inhibited drug release.

[0076] Comparative Example 1 was compared with Example 1. In this comparative example, the fiber produced had microscopic defects such as flattening and severe adhesion due to insufficient acetone solvent in the spinning solution. This is because acetone is a highly volatile solvent, and a low acetone content in the system directly reduces the solvent evaporation rate of the spinning jet. During coaxial electrospinning, the solvent cannot evaporate sufficiently, and the jet remains in a highly viscous liquid state. After multiple adjacent jets reach the receiving substrate, they are not completely solidified, and mutual fusion and spreading occur at the interface, eventually forming a flat, ribbon-like structure. The fiber boundaries are completely adhered and fused, making it difficult to construct a continuous fiber structure. The porous network has two drawbacks from the perspective of drug delivery: First, the fiber adhesion and fusion will form a large number of closed encapsulation areas, and the active drug will be trapped in the dense inner layer of the polymer matrix, lacking mass transfer channels for outward diffusion; Second, the specific surface area will be greatly reduced, the effective contact interface between the fiber and the release medium will be sharply reduced, and the resistance to drug molecule dissolution and diffusion will be significantly increased. Ultimately, this will result in a slow drug release rate and a low cumulative release amount, which cannot meet the requirements of long-term antibacterial effect during the proliferative phase of wounds and the need to protect tissue repair over time.

[0077] Example 2

[0078] A method for preparing a core-shell structured nanofiber membrane, comprising the following steps:

[0079] (1) Prepare the shell spinning solution;

[0080] First, cellulose acetate (weight-average molecular weight 7.27 × 10⁻⁶) is... 4 g·mol -1 A homogeneous, transparent solution with a concentration of 15% (w / w) was prepared using sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) and solvent A. Sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) was then added to the solution. 4 g·mol -1 The solution was magnetically stirred until completely dissolved, and allowed to stand for 24 hours to obtain a shell spinning solution with a viscosity of 370 mPa·s. Solvent A was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of sodium carboxymethyl cellulose was 1.5% of the mass of cellulose acetate.

[0081] (2) Prepare the core spinning solution;

[0082] First, polypropylene carbonate (weight average molecular weight 6.9 × 10⁻⁶) is used. 4 g·mol -1A spinning solution with a molecular weight distribution index of 1.20 and solvent B was prepared to a concentration of 10% (w / w). Then, silver sulfadiazine was added to the solution, followed by ultrasonic treatment for 30 min to ensure uniform dispersion of the silver sulfadiazine, resulting in a core spinning solution with a stable viscosity of 266 mPa·s. Solvent B was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of silver sulfadiazine was 7.5% of the mass of polypropylene carbonate.

[0083] (3) The shell spinning solution and the core spinning solution are coaxially electrospun to obtain a fiber membrane. The fiber membrane is then placed in a vacuum oven and dried for 48 hours to remove the solvent in the sample, thus obtaining a core-shell structured nanofiber membrane. The inner needle (23G specification) is used to deliver the core solution, and the outer needle (18G specification) is used to deliver the shell solution.

[0084] The process parameters for coaxial electrospinning include: shell solution flow rate 0.05 mm / min, core solution flow rate 0.16 mm / min, forward voltage 29 kV, reverse voltage -3 kV, receiving distance 13 cm, receiving speed 80 rpm, ambient temperature 28°C, and ambient relative humidity 55%.

[0085] The final core-shell structured nanofiber membrane is composed of core-shell structured nanofibers;

[0086] The shell of the core-shell nanofiber consists of cellulose acetate as a substrate and sodium carboxymethyl cellulose embedded therein in the form of discrete hydrophilic sites, while the core consists of polypropylene carbonate as a substrate and silver sulfadiazine coated therein; the diameter of the core-shell nanofiber is 783±98 nm, and the diameter of the core is 178±10 nm.

[0087] The core-shell structured nanofiber membrane has a thickness of 0.49 mm and a specific surface area of ​​68.47 m². 2 / g;

[0088] The initial water contact angle of the core-shell structured nanofiber membrane was 119.2±3.9°. It took 324±23s to reach a 90° water contact angle from the initial water contact angle, 173±15s to reach a 45° water contact angle from the 90° water contact angle, and 79±28s to reach a 0° water contact angle from the 45° water contact angle.

[0089] After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 41.9% after 1 hour, 65.3% after 2 hours, 78.3% after 1 day, and 86.5% after 2 days. It took 14 days to reach a 100% cumulative drug release rate.

[0090] The core-shell structured nanofiber membrane exhibited a 24-hour inhibition rate of 99.99% against Gram-positive bacteria and 99.99% against Gram-negative bacteria.

[0091] Comparative Example 2

[0092] A method for preparing a core-shell structured nanofiber membrane is basically the same as in Example 2, except that: in step (1), the mass of sodium carboxymethyl cellulose is 1.1% of the mass of cellulose acetate, and the viscosity of the shell spinning solution is 355 mPa·s.

[0093] The core-shell structured nanofiber membrane obtained had an initial water contact angle of 125.5°. It took 657±25s to reach a water contact angle of 90° from the initial water contact angle, 236±22s to reach a water contact angle of 45° from 90°, and 154±23s to reach a water contact angle of 0° from 45°.

[0094] After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 22.8% after 1 hour, 31.5% after 2 hours, 49.2% after 1 day, and 61.8% after 2 days. It took 22 days to reach a 100% cumulative drug release rate.

[0095] The core-shell structured nanofiber membrane exhibited a 24-hour inhibition rate of 95.45% against Gram-positive bacteria and 96.58% against Gram-negative bacteria.

[0096] Comparing Comparative Example 2 and Example 2, it can be seen that the drug release time of the core-shell structured nanofiber membrane prepared in this comparative example is significantly prolonged, and the antibacterial rate cannot reach 99.99% after 24 hours. This is because the content of sodium carboxymethyl cellulose used in the shell layer of this comparative example is relatively small, resulting in a reduction in the amount of sodium carboxymethyl cellulose with hydrophilic points in the prepared fiber shell layer. When the fiber comes into contact with wound fluid or exudate, the drug release channels formed are reduced, ultimately leading to a prolonged drug release time and reduced antibacterial performance of the fiber membrane, which cannot meet the requirements of long-term antibacterial effect during the wound proliferative phase and the protection of tissue repair.

[0097] Example 3

[0098] A method for preparing a core-shell structured nanofiber membrane, comprising the following steps:

[0099] (1) Prepare the shell spinning solution;

[0100] First, cellulose acetate (weight-average molecular weight 7.27 × 10⁻⁶) is... 4 g·mol -1A homogeneous, transparent solution with a concentration of 15% (w / w) was prepared using sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) and solvent A. Sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) was then added to the solution. 4 g·mol -1 The solution was magnetically stirred until completely dissolved, and allowed to stand for 24 hours to obtain a shell spinning solution with a viscosity of 370 mPa·s. Solvent A was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of sodium carboxymethyl cellulose was 1.5% of the mass of cellulose acetate.

[0101] (2) Prepare the core spinning solution;

[0102] First, polypropylene carbonate (weight average molecular weight 6.9 × 10⁻⁶) is used. 4 g·mol -1 A spinning solution with a molecular weight distribution index of 1.20 and solvent B was prepared to a concentration of 10% (w / w). Then, silver sulfadiazine was added, and the solution was ultrasonically treated for 30 min to ensure uniform dispersion of the silver sulfadiazine, resulting in a core spinning solution with a stable viscosity of 271 mPa·s. Solvent B was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of silver sulfadiazine was 10% of the mass of polypropylene carbonate.

[0103] (3) The shell spinning solution and the core spinning solution are coaxially electrospun to obtain a fiber membrane. The fiber membrane is then placed in a vacuum oven and dried for 48 hours to remove the solvent in the sample, thus obtaining a core-shell structured nanofiber membrane. The inner needle (23G specification) is used to deliver the core solution, and the outer needle (18G specification) is used to deliver the shell solution.

[0104] The process parameters for coaxial electrospinning include: shell solution flow rate 0.06 mm / min, core solution flow rate 0.2 mm / min, forward voltage 30 kV, reverse voltage -2 kV, receiving distance 15 cm, receiving speed 100 rpm, ambient temperature 30°C, and ambient relative humidity 60%.

[0105] The final core-shell structured nanofiber membrane is composed of core-shell structured nanofibers;

[0106] The shell of the core-shell nanofiber consists of cellulose acetate as a substrate and sodium carboxymethyl cellulose embedded therein in the form of discrete hydrophilic sites, while the core consists of polypropylene carbonate as a substrate and silver sulfadiazine coated therein; the diameter of the core-shell nanofiber is 905±101 nm, and the diameter of the core is 180±15 nm.

[0107] The core-shell structured nanofiber membrane has a thickness of 0.52 mm and a specific surface area of ​​84.65 m². 2 / g;

[0108] The initial water contact angle of the core-shell structured nanofiber membrane was 117.4±2.4°. It took 291±22s to reach a 90° water contact angle from the initial water contact angle, 26±18s to reach a 45° water contact angle from the 90° water contact angle, and 66±32s to reach a 0° water contact angle from the 45° water contact angle.

[0109] After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 36.7% after 1 hour, 62.2% after 2 hours, 78.1% after 1 day, and 84.2% after 2 days. It took 14 days to reach a 100% cumulative drug release rate.

[0110] The core-shell structured nanofiber membrane exhibited a 24-hour inhibition rate of 99.99% against Gram-positive bacteria and 99.99% against Gram-negative bacteria.

[0111] Comparative Example 3

[0112] A method for preparing a composite fiber membrane is basically the same as in Example 3, except that coaxial electrospinning is replaced by conjugate spinning in step (3).

[0113] The process parameters for conjugate spinning include: the spinning rate of the spinning solution prepared in step (1) is 0.2 mm / min, the voltage of the spinning solution prepared in step (1) is 20 kV, the spinning rate of the spinning solution prepared in step (2) is 0.06 mm / min, the voltage of the spinning solution prepared in step (2) is -12 kV, the receiving distance is 15 cm, the receiving speed is 100 rpm, the ambient temperature is 30 ℃, and the ambient relative humidity is 65%.

[0114] The final composite fiber membrane was obtained by physical blending of polypropylene carbonate (silver sulfadiazine) fibers and cellulose acetate (sodium carboxymethyl cellulose) fibers, rather than a core-shell structure;

[0115] After being soaked in PBS buffer at pH 7.4, the cumulative drug release rate of the composite fiber membrane was 50.4% after 1 hour, 88.4% after 2 hours, 95.3% after 1 day, and 97.8% after 2 days. It took 3 days to reach a 100% cumulative drug release rate.

[0116] Comparing Comparative Example 3 and Example 3, it can be seen that the composite fiber membrane prepared in this comparative example releases the drug too quickly and does not achieve the effect of sustained drug release. This is because silver sulfadiazine is directly dispersed in polypropylene carbonate fiber without a cellulose acetate shell for sustained release.

[0117] The performance of the fiber membranes prepared in Examples 1-3 and Comparative Example 3 was compared, and the results are as follows: Figure 6 and Figure 6 As shown;

[0118] from Figure 5 As can be seen, the nanofiber membrane prepared in Comparative Example 3 exhibits a significant "burst release" phenomenon, with a cumulative drug release rate as high as 50.4% after 1 hour, and completes drug release within 1 day (cumulative drug release rate reaches 95.3%). In contrast, the nanofiber membranes in Examples 1-3 have a core-shell structure, which significantly delays drug release. The drug release rate is dynamically controlled by the wound healing process, with a cumulative drug release rate of 75.0%-78.3% after 1 day, 81.2%-86.5% after 2 days, and then enters a stable sustained-release phase lasting up to 14 days, with the cumulative drug release rate eventually reaching 100%. This result is attributed to the dual diffusion barrier effect of the core-shell structure: the polypropylene carbonate core layer and the cellulose acetate / sodium carboxymethyl cellulose shell jointly regulate the dissolution rate of silver sulfadiazine, inhibiting the initial burst release, prolonging the effective antibacterial period, and creating a sterile environment for wound healing.

[0119] from Figure 6 , Figure 7 As can be seen, the nanofiber membranes of Examples 1-3 have highly efficient antibacterial activity against Staphylococcus aureus and Escherichia coli (antibacterial inhibition rate ≥99.98%). This result also shows that the nanofiber membranes of Examples 1-3, through core-shell structure design, effectively regulate the release behavior of silver ions while ensuring highly efficient antibacterial activity, and achieve functional synergy of "rapid antibacterial effect" and "long-term maintenance". This provides a new material design and theoretical basis for developing a new generation of intelligent and multifunctional dressings for the repair of infected wounds.

[0120] Example 4

[0121] A method for preparing a core-shell structured nanofiber membrane, comprising the following steps:

[0122] (1) Prepare the shell spinning solution;

[0123] First, cellulose acetate (weight-average molecular weight 7.27 × 10⁻⁶) is... 4 g·mol -1 A homogeneous, transparent solution with a concentration of 15% (w / w) was prepared using sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) and solvent A. Sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) was then added to the solution. 4 g·mol -1The solution was magnetically stirred until completely dissolved, and allowed to stand for 24 hours to obtain a shell spinning solution with a viscosity of 365 mPa·s. Solvent A was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of sodium carboxymethyl cellulose was 1.2% of the mass of cellulose acetate.

[0124] (2) Prepare the core spinning solution;

[0125] First, polypropylene carbonate (weight average molecular weight 6.9 × 10⁻⁶) is used. 4 g·mol -1 A spinning solution with a molecular weight distribution index of 1.20 and solvent B was prepared to a concentration of 10% (w / w). Then, silver sulfadiazine was added, and the solution was ultrasonically treated for 30 min to ensure uniform dispersion of the silver sulfadiazine, resulting in a core spinning solution with a stable viscosity of 267 mPa·s. Solvent B was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of silver sulfadiazine was 8% of the mass of polypropylene carbonate.

[0126] (3) The shell spinning solution and the core spinning solution are coaxially electrospun to obtain a fiber membrane. The fiber membrane is then placed in a vacuum oven and dried for 48 hours to remove the solvent in the sample, thus obtaining a core-shell structured nanofiber membrane. The inner needle (23G specification) is used to deliver the core solution, and the outer needle (18G specification) is used to deliver the shell solution.

[0127] The process parameters for coaxial electrospinning include: shell solution flow rate 0.06 mm / min, core solution flow rate 0.18 mm / min, forward voltage 28 kV, reverse voltage -4 kV, receiving distance 10 cm, receiving rotation speed 60 rpm, ambient temperature 28°C, and ambient relative humidity 65%.

[0128] The final core-shell structured nanofiber membrane is composed of core-shell structured nanofibers;

[0129] The shell of the core-shell nanofiber consists of cellulose acetate as a substrate and sodium carboxymethyl cellulose embedded therein in the form of discrete hydrophilic sites, while the core consists of polypropylene carbonate as a substrate and silver sulfadiazine coated therein; the diameter of the core-shell nanofiber is 623±48 nm, and the diameter of the core is 173±8 nm.

[0130] The core-shell structured nanofiber membrane has a thickness of 0.38 mm and a specific surface area of ​​76.93 m². 2 / g;

[0131] The initial water contact angle of the core-shell structured nanofiber membrane was 126.1±1.8°. It took 541±25s to reach a 90° water contact angle from the initial water contact angle, 125±12s to reach a 45° water contact angle from the 90° water contact angle, and 83±19s to reach a 0° water contact angle from the 45° water contact angle.

[0132] After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 28.9% after 1 hour, 51.5% after 2 hours, 69.8% after 1 day, and 78.3% after 2 days. It took 14 days to reach a 100% cumulative drug release rate.

[0133] The core-shell structured nanofiber membrane exhibited a 24-hour inhibition rate of 99.98% against Gram-positive bacteria and 99.99% against Gram-negative bacteria.

[0134] Example 5

[0135] A method for preparing a core-shell structured nanofiber membrane, comprising the following steps:

[0136] (1) Prepare the shell spinning solution;

[0137] First, cellulose acetate (weight-average molecular weight 7.27 × 10⁻⁶) is... 4 g·mol -1 A homogeneous, transparent solution with a concentration of 15% (w / w) was prepared using sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) and solvent A. Sodium carboxymethyl cellulose (with a weight-average molecular weight of 9.0 × 10⁻⁶) was then added to the solution. 4 g·mol -1 The solution was magnetically stirred until completely dissolved, and allowed to stand for 24 hours to obtain a shell spinning solution with a viscosity of 383 mPa·s. Solvent A was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of sodium carboxymethyl cellulose was 2% of the mass of cellulose acetate.

[0138] (2) Prepare the core spinning solution;

[0139] First, polypropylene carbonate (weight average molecular weight 6.9 × 10⁻⁶) is used. 4 g·mol -1 A spinning solution with a molecular weight distribution index of 1.20 and solvent B was prepared to a concentration of 10% (w / w). Then, silver sulfadiazine was added, and the solution was ultrasonically treated for 30 min to ensure uniform dispersion of the silver sulfadiazine, resulting in a core spinning solution with a stable viscosity of 269 mPa·s. Solvent B was a mixture of acetone and DMAC in a volume ratio of 2:1, and the mass of silver sulfadiazine was 9% of the mass of polypropylene carbonate.

[0140] (3) The shell spinning solution and the core spinning solution are coaxially electrospun to obtain a fiber membrane. The fiber membrane is then placed in a vacuum oven and dried for 48 hours to remove the solvent in the sample, thus obtaining a core-shell structured nanofiber membrane. The inner needle (23G specification) is used to deliver the core solution, and the outer needle (18G specification) is used to deliver the shell solution.

[0141] The process parameters for coaxial electrospinning include: shell solution flow rate 0.04 mm / min, core solution flow rate 0.12 mm / min, forward voltage 30 kV, reverse voltage -2 kV, receiving distance 12 cm, receiving rotation speed 80 rpm, ambient temperature 26°C, and ambient relative humidity 45%.

[0142] The final core-shell structured nanofiber membrane is composed of core-shell structured nanofibers;

[0143] The shell of the core-shell nanofiber consists of cellulose acetate as a substrate and sodium carboxymethyl cellulose embedded therein in the form of discrete hydrophilic sites, while the core consists of polypropylene carbonate as a substrate and silver sulfadiazine coated therein; the diameter of the core-shell nanofiber is 806±124 nm, and the diameter of the core is 182±12 nm.

[0144] The core-shell structured nanofiber membrane has a thickness of 0.45 mm and a specific surface area of ​​58.69 m². 2 / g;

[0145] The initial water contact angle of the core-shell structured nanofiber membrane was 120.3±1.5°. It took 212±31s to reach a water contact angle of 90° from the initial water contact angle, 18±6s to reach a water contact angle of 45° from 90°, and 27±16s to reach a water contact angle of 0° from 45°.

[0146] After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 42.6% after 1 hour, 68.3% after 2 hours, 79.7% after 1 day, and 89.9% after 2 days. It took 14 days to reach a 100% cumulative drug release rate.

[0147] The core-shell structured nanofiber membrane exhibited a 24-hour inhibition rate of 99.99% against Gram-positive bacteria and 99.99% against Gram-negative bacteria.

[0148] Comparative Example 4

[0149] A method for preparing a nanofiber membrane is basically the same as in Example 5, except that in step (1), sodium carboxymethyl cellulose is replaced with an equal mass of hydroxyethyl cellulose (weight-average molecular weight of 4.52 × 10⁻⁶). 4The viscosity of the resulting shell spinning solution was 347 mPa·s (g·mol⁻¹, molecular weight distribution index of 1.14).

[0150] The core-shell nanofiber membranes that were finally prepared showed a cumulative drug release rate of 47.3% after 1 hour, 68.5% after 2 hours, 75.8% after 1 day, and 95.2% after 2 days after 1 day. It took 3 days to reach a cumulative drug release rate of 100%.

[0151] A comparison of Comparative Example 4 and Example 5 shows that the SET and TEM images of the core-shell structured nanofiber membrane in this comparative example are as follows: Figure 9 As shown in the figure, the addition of hydroxyethyl cellulose effectively reduces the viscosity of the spinning solution, altering the rheological behavior of the spinning system. This ultimately results in uneven fiber diameter, preventing the formation of a continuous core-shell fiber membrane with a complete and uniform coating. Consequently, drug release becomes uncontrollable, and the overall drug release cycle is shortened. This is because the incorporation of hydroxyethyl cellulose weakens the physical entanglement network between polymer chains, significantly reducing the viscoelasticity and deformation resistance of the spinning solution. Under the stretching effect of the high-voltage electric field in coaxial electrospinning, the low-viscosity fluid struggles to maintain a stable jet morphology, easily leading to overstretching, disordered splitting, and random refinement. Simultaneously, the specific surface area increases dramatically after jet refinement, significantly accelerating solvent evaporation and rapidly solidifying and locking in irregular ultrafine fiber morphologies. This unstable jet forming behavior completely disrupts the coaxial coating matching relationship between the inner and outer spinning solutions, preventing the shell polymer from uniformly and continuously coating the core structure, ultimately resulting in composite fibers with uneven morphology and incomplete core-shell structures. Furthermore, the irregular fibrous structure causes significant differences in drug diffusion resistance, resulting in localized rapid drug release defects. Ultimately, this completely disrupts stable sustained-release kinetics, leading to uncontrollable drug release behavior and a shortened overall drug release cycle. Consequently, it fails to meet the requirements for long-lasting antibacterial action during the wound proliferative phase and for supporting the sequential repair of tissues.

[0152] Comparative Example 5

[0153] A method for preparing a core-shell structured fibrous membrane is basically the same as in Example 5, except that in step (1), sodium carboxymethyl cellulose is replaced with an equal mass of hydroxypropyl cellulose (weight-average molecular weight of 6.58 × 10⁻⁶). 4 The viscosity of the resulting shell spinning solution was 398 mPa·s (g·mol⁻¹, molecular weight distribution index of 1.35).

[0154] The final scanning electron microscope image of the core-shell structured fibrous membrane is shown below. Figure 10 As shown, the shell of the core-shell structure fiber is composed of cellulose acetate as the substrate and hydroxypropyl cellulose embedded therein in the form of discrete hydrophilic sites.

[0155] The core-shell structure fibers have a diameter of 1.66 ± 0.39 μm and a specific surface area of ​​15.06 m². 2 / g. The cumulative drug release rate was 16.5% in 1 hour, 28.9% in 2 hours, 38.2% in 1 day, 44.3% in 2 days, and 75.6% by day 14. The excessively thick shell layer hindered drug release.

[0156] Comparing Comparative Example 5 and Example 5, it can be seen that the composite fiber membrane prepared in this comparative example has a very large diameter. This is because hydroxypropyl cellulose is a non-ionic, water-soluble cellulose derivative. Adding it to the shell spinning solution increases the viscosity of the solution. Increased viscosity leads to a large amount of polymer entanglement, increasing flow resistance, inhibiting jet whipping and splitting, making it difficult for the electric field to refine the coarse jet, and further increasing the fiber diameter due to molecular chain retraction. Furthermore, according to the core structural principles of electrospun fiber materials (fiber specific surface area is significantly negatively correlated with fiber diameter), the fibers prepared in this comparative example are micron-sized fibers, and the specific surface area of ​​a single fiber decreases geometrically with increasing particle size. The stacking of micron-sized fibers is more loose, resulting in large pore sizes and a small number of pores formed by the overlap between fibers, significantly reducing the effective adsorption interface and porous channels provided per unit mass of fiber membrane. Ultimately, this leads to a significantly lower BET specific surface area for the core-shell fiber membrane compared to pure nanofiber membrane materials.

[0157] Furthermore, the scale characteristics and hydrophilic modified structure of non-nanoscale core-shell fibers together determine their unique drug sustained-release behavior: on the one hand, the increased fiber diameter and decreased specific surface area significantly reduce the effective contact area between the fiber membrane and the release medium, resulting in a significant decrease in the interfacial mass transfer efficiency of medium permeation and drug dissolution; on the other hand, the thicker wall of the micron-scale fiber matrix significantly lengthens the diffusion path of the drug within the polymer matrix, greatly increasing the mass transfer resistance. Macroscopically, this manifests as a slower drug release rate, which cannot meet the requirements for long-term antibacterial action during the proliferative phase of wounds and for supporting the sequential repair of tissues.

[0158] Comparative Example 6

[0159] A method for preparing a core-shell structured nanofiber membrane is basically the same as in Example 5, except that the mass of sodium carboxymethyl cellulose in step (1) is 2.1% of the mass of cellulose acetate.

[0160] The initial water contact angle of the core-shell structured nanofiber membrane was 118.5±2.7°. It took 175±24s to reach a water contact angle of 90° from the initial water contact angle, 15±4s to reach a water contact angle of 45° from 90°, and 12±3s to reach a water contact angle of 0° from 45°.

[0161] After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 48.4% after 1 hour, 70.5% after 2 hours, 85.3% after 1 day, and 94.8% after 2 days. It took 4 days to reach a 100% cumulative drug release rate.

[0162] Comparing Comparative Example 6 and Example 5, it can be seen that the drug release time of the core-shell structured nanofiber membrane prepared in this comparative example is shortened, resulting in a drug burst release. This is because the content of sodium carboxymethyl cellulose used in the shell layer of this comparative example is relatively high, which leads to an increase in the amount of sodium carboxymethyl cellulose with hydrophilic points in the prepared fiber shell layer. When the fiber comes into contact with wound fluid or exudate, too many drug release channels are formed, which in turn leads to an increase in drug release channels, a shortened drug release time, and a drug burst release phenomenon. This cannot meet the requirements of long-term antibacterial effect during the wound proliferative phase and the protection of tissue repair.

Claims

1. A core-shell structured nanofiber, characterized in that, The shell layer includes cellulose acetate as a substrate and sodium carboxymethyl cellulose embedded therein in the form of discrete hydrophilic sites. The core layer includes polypropylene carbonate as a substrate and a drug encapsulated therein, the drug being silver sulfadiazine. The mass of sodium carboxymethyl cellulose in the shell layer is 1.2% to 2.0% of the mass of cellulose acetate.

2. The core-shell structured nanofiber according to claim 1, characterized in that, The diameter of the core-shell nanofibers is 575~1035.2 nm, and the diameter of the core layer is 164~195 nm.

3. The core-shell structured nanofiber according to claim 1, characterized in that, The mass of the drug in the core layer is 5% to 10% of the mass of polypropylene carbonate.

4. The core-shell structured nanofiber according to claim 1, characterized in that, The weight-average molecular weight of cellulose acetate is 7.27 × 10⁻⁶. 4 g·mol -1 The molecular weight distribution index is 1.67; the weight-average molecular weight of sodium carboxymethyl cellulose is 9.0 × 10⁻⁶. 4 g·mol -1 The molecular weight distribution index is 1.01; the weight-average molecular weight of polypropylene carbonate is 6.9 × 10⁻⁶. 4 g·mol -1 The molecular weight distribution index is 1.

20.

5. A core-shell structured nanofiber membrane, characterized in that, It is composed of a core-shell structured nanofiber as described in any one of claims 1 to 4.

6. The core-shell structured nanofiber membrane according to claim 5, characterized in that, The core-shell structured nanofiber membranes have a thickness of 0.52–0.38 mm and a specific surface area of ​​58.49–84.65 m². 2 / g; The initial water contact angle of the core-shell structured nanofiber membrane is 115~127.9°, the time taken to reach a 90° water contact angle is 181~566s, the time taken to reach a 45° water contact angle is 8~206s, and the time taken to reach a 0° water contact angle is 11~127s. After being soaked in PBS buffer at pH 7.4, the core-shell nanofiber membrane showed a cumulative drug release rate of 28.9%–42.6% after 1 hour, 51.5%–68.3% after 2 hours, 69.8%–79.7% after 1 day, and 78.3%–89.9% after 2 days. It took 14 days to reach a 100% cumulative drug release rate. The core-shell structured nanofiber membrane exhibits a 24-hour inhibition rate of ≥99.98% against Gram-positive bacteria and ≥99.99% against Gram-negative bacteria.

7. A method for preparing a core-shell structured nanofiber membrane as described in claim 5 or 6, characterized in that, Core-shell structured nanofiber membranes are obtained by coaxial electrospinning of the shell spinning solution and the core spinning solution. The solvents in both the shell spinning solution and the core spinning solution are a mixture of acetone and DMAC in a volume ratio of 2:

1. The viscosity of the shell spinning solution is 365~383 mPa·s, and the viscosity of the core spinning solution is 263~271 mPa·s.

8. The method according to claim 7, characterized in that, The process parameters for coaxial electrospinning include: shell solution flow rate 0.04~0.06 mm / min, core solution flow rate 0.12~0.20 mm / min, forward voltage 28~30 kV, reverse voltage -2~-4 kV, receiving distance 10~15 cm, receiving rotation speed 60~100 rpm, ambient temperature 28±2°C, and ambient relative humidity 55±10%.

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