Multifunctional micro-nano interwoven fiber membrane drug-loaded dressing and preparation method thereof

Abstract

The application discloses a multifunctional micro-nano interwoven fiber membrane drug-loaded dressing and a preparation method thereof, and belongs to the technical field of biomedical materials. Mainly including: using electrostatic-rotary jet spinning technology, preparing a natural polymer / PLA interwoven drug-loaded fiber membrane, through regulating the content of the PLA fiber, optimizing the pore structure, mechanical properties and wettability of the fiber membrane and other performances, loading active drugs, and realizing the preparation of multifunctional drug-loaded dressings with antibacterial, anti-inflammatory, hemostatic and healing promoting functions. The obtained fiber membrane is improved in mechanical strength, porosity, moisture permeability, liquid absorption and biocompatibility, and is suitable for medical dressings for acute trauma and arterial hemorrhagic wounds, chronic non-healing wounds, deep burn wounds and the like, and is especially suitable for medical dressings for moderate and severe exudative wounds.

Description

Technical Field

[0001] This invention belongs to the field of biomedical materials technology, and specifically relates to a multifunctional micro-nano interwoven fiber membrane drug-loaded dressing and its preparation method. Background Technology

[0002] As modern medicine advances towards precision and personalization, the research goals of drug delivery materials have expanded from single drug carriers to multi-drug loading, controlled drug release, improved drug utilization, and reduced drug resistance and toxic side effects. Among these, nanofiber drug-loaded systems have become a research hotspot due to their structural advantages of large specific surface area and high porosity. However, existing nanofiber drug-loaded systems have significant drawbacks: uncontrollable drug release rates and limited material functionality, making it difficult to simultaneously achieve mechanical properties, biocompatibility, and controllable drug release, thus failing to meet the increasingly stringent demands of clinical applications.

[0003] Existing technologies prepare composite fiber membranes by mixing two or more polymers. However, the significant differences in physicochemical properties between different polymers lead to uneven fiber morphology, resulting in beading or adhesion phenomena, which affect the overall performance of the fiber membrane. Coaxial spinning technology can effectively reduce drug burst release problems by preparing core-sheath structure fibers. However, traditional coaxial spinning processes are complex, require high precision spinnerets, and have high industrialization costs, thus hindering its large-scale promotion.

[0004] To address the aforementioned limitations, researchers have attempted to optimize the performance and yield of fibrous membranes in recent years, but significant shortcomings remain. Literature CN106283399A discloses a method for preparing silk fibroin / polycaprolactone composite nanofiber membranes via electrospinning, achieving slow drug release and increased specific surface area. However, the mechanical strength of the fibrous membranes prepared by this method is insufficient to meet the mechanical requirements of medical dressings, and the porosity is below 80%, making it unsuitable for exudative wound scenarios. Furthermore, the low spinning rate and limited membrane width hinder the large-scale production of medical dressings.

[0005] To overcome the shortcomings of traditional nanofiber drug-loaded dressings, such as low mechanical strength and disintegration upon contact with water, literature CN107142610A discloses a polylactic acid fiber interwoven dressing and its preparation method, which achieves high mechanical stability in a wet state by constructing a polylactic acid fiber interwoven network. However, this method has defects such as low drug loading and severe burst release, and cannot meet the needs of wet wound healing scenarios that require continuous and stable delivery of water-soluble active molecules.

[0006] Literature CN117681354A discloses a polylactic acid / silk fibroin composite fiber membrane and its preparation method, which improves the biocompatibility and drug loading properties of the fiber membrane. However, this method results in uniform fiber diameter, low porosity, insufficient moisture permeability, poor compatibility between the drug and polymer molecules, and can only achieve drug release at a single rate, making it impossible to regulate the drug release cycle. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to overcome the shortcomings of the prior art and provide a multifunctional micro-nano interwoven fiber membrane drug-loaded dressing and its preparation method, specifically including the following steps: S1. Add PLA particles to a DCM / DMF binary solvent with a DCM to DMF volume ratio of 9:1, stir at room temperature until completely dissolved, prepare spinning solution A, and let stand to remove bubbles before use; S2. Weigh the natural polymeric drug-carrying material and the active drug, add solvent, stir at room temperature until completely dissolved, prepare spinning solution B, and let stand to remove bubbles before use; S3. The spinning solution A described in S1 and the spinning solution B described in S2 are respectively injected into a dual-cavity spinneret for electrostatic-rotational jet spinning to obtain an interwoven fiber membrane drug-loaded dressing.

[0008] The natural polymeric drug-carrying material described in S2 includes protein-based polymers and polysaccharide polymers; the protein-based polymers are selected from one or more of silk fibroin, collagen, gelatin and zein; the polysaccharide polymers are selected from one or more of lotus seed starch, sodium alginate, chitosan, cellulose, hyaluronic acid, pectin, agarose, dextran, xanthan gum, heparin and cyclodextrin.

[0009] The active drug described in S2 is one or more of the following: antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), natural polyphenolic compounds, polypeptides, and hemostatic agents. Specifically, the antibiotic is one or more of tetracycline, levofloxacin, and vancomycin. The NSAID is one or more of ibuprofen, naproxen, and diclofenac. The natural polyphenolic compound is one or more of lotus polyphenols, curcumin, quercetin, resveratrol, and shikonin. The polypeptide is one or more of ε-polylysine, antimicrobial peptides, thrombin, and epidermal growth factor.

[0010] The solvent mentioned in S2 is one or more of anhydrous formic acid, anhydrous acetic acid, and hexafluoroisopropanol.

[0011] The antibiotics in S2 have a mass ratio of 5% to 20%; the nonsteroidal anti-inflammatory drugs have a mass ratio of 1% to 10%; the natural polyphenols have a mass ratio of 1% to 10%; when the polypeptide is ε-polylysine or an antimicrobial peptide, its mass ratio is 1% to 10%; when the polypeptide is thrombin or epidermal growth factor, its mass ratio is 0.001% to 1%.

[0012] The spinneret of the dual-chamber spinneret described in S3 has a spinneret configuration of 1~4:4~1; the motor speed is 2500~3500 rpm and the voltage is 4~10 kV.

[0013] The natural polymer fibers have a diameter of 0.5~5 μm, the PLA fibers have a diameter of 5~20 μm, the fiber ratio is 1~9:9~1, the porosity is 60%~90%, the dressing has a moisture permeability of 1000~5000 g / (m²·24 h), an air permeability of 50~200 mm / s, a tensile strength of 1~10 MPa, a liquid absorbency of 10~20 g / g, and a cell activity of 70%~120%.

[0014] Preferably, scanning electron microscopy is used to observe the surface morphology, fiber diameter, and pore structure of the fiber membrane; an electronic universal testing machine is used to test the mechanical properties of the fiber membrane; a dynamic contact angle meter is used to test the wettability of the fiber membrane; mercury intrusion porosimetry is used to test the pore structure of the fiber membrane; the cup method is used to test the water permeability (WVTR), and the immersion method is used to test the liquid absorption; a water flux meter is used to test the water flux of the fiber membrane; the CCK-8 method is used to test cytotoxicity; infrared spectroscopy and X-ray diffraction are used to characterize the interaction between the drug and the polymer and the drug crystallization state; an ultraviolet spectrophotometer is used to detect the drug concentration and calculate the cumulative drug release; and a self-made circulation device is used to detect the drug release behavior and analyze the dynamic drug release pattern.

[0015] The beneficial effects of this invention are: (1) In this invention, PLA fibers in the micro-nano cross-scale interwoven structure play a reinforcing and protective role, which can effectively slow down the damage of natural polymer fibers, improve the stability of wet environment, and not affect its drug loading and release function; natural polymer fibers play a drug loading function; the two fibers work together to achieve a balance of "material-structure-performance-application", which breaks through the defect that traditional composite fiber membrane structure and function are difficult to balance.

[0016] (2) In this invention, the design of the micro-nano cross-scale interwoven structure significantly improves the mechanical strength of the fiber membrane, solving the bottleneck of low absolute strength of traditional nanofiber membranes; and it still maintains good structural and mechanical stability after water permeation, meeting the requirements for wet use.

[0017] (3) In this invention, the fiber membrane has high porosity, high moisture permeability, and excellent liquid absorption performance, which is superior to most commercial dressings and is suitable for moderate to severe exudative wounds; at the same time, the hydrophobicity of the fiber membrane can be adjusted.

[0018] (4) In this invention, the wettability of the fiber membrane can be controlled by adjusting the PLA fiber content, thereby regulating the drug release behavior of the fiber membrane and achieving precise controlled drug release. At the same time, the structure maintains good structural stability under the impact of different flow rate buffers, which can meet the needs of dynamic release scenarios such as hemodialysis and natural rivers. Attached Figure Description

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0020] Figure 1 Flowchart of the preparation process for multifunctional micro-nano interwoven fiber membrane drug-loaded dressing; Figure 2 This is a SEM image of the morphology of the multifunctional micro-nano interwoven fiber membrane drug-loaded dressing in Example 1; Figure 3 The stress-strain curve of the multifunctional micro-nano interwoven fiber membrane drug-loaded dressing in Example 1 is shown. Figure 4 The curves show the moisture permeability and absorbency of the multifunctional micro-nano interwoven fiber membrane drug-loaded dressing in Example 1; where (a) is the moisture permeability of the multifunctional micro-nano interwoven fiber membrane drug-loaded dressing, and (b) is the absorbency of the multifunctional micro-nano interwoven fiber membrane drug-loaded dressing. Figure 5 The relative cell activity of the multifunctional micro-nano interwoven fiber membrane drug-loaded dressing in Example 1; Figure 6 The static cumulative drug release curve of the multifunctional micro-nano interwoven fiber membrane drug-loaded dressing in Example 1; Figure 7 The water flux of PLA fiber membrane drug-loaded dressing fiber membrane and SF / PCL / PVP-PLA interwoven fiber membrane under different water pressures in Example 2; where (a) is under 1 kPa water pressure, (b) is under 3 kPa water pressure, and (c) is under 5 kPa water pressure. Figure 8 The figures for Example 2 are cumulative drug release curves of IBU@SF / PCL / PVP-PLA interwoven fiber membranes with different PLA fiber contents at different PBS buffer flow rates; where (a) is the drug release curve at 1 ms. -1 (b) represents a content of 3 ms -1 (c) represents a content of 6 ms -1 (d) represents the content of 9 ms -1 . Detailed Implementation

[0021] To facilitate understanding by those skilled in the art, the present invention will be further described below with reference to embodiments and accompanying drawings. The content mentioned in the embodiments is not intended to limit the present invention.

[0022] like Figure 1 As shown, this invention provides a method for preparing a multifunctional micro / nano interwoven fiber membrane drug-loaded dressing, comprising the following steps: S1. Add PLA particles to a DCM / DMF binary solvent with a DCM to DMF volume ratio of 9:1, stir at room temperature until completely dissolved, prepare spinning solution A, and let stand to remove bubbles before use; S2. Weigh the natural polymeric drug-carrying material and the active drug, add solvent, stir at room temperature until completely dissolved, prepare spinning solution B, and let stand to remove bubbles before use; S3. The spinning solution A described in S1 and the spinning solution B described in S2 are respectively injected into a dual-cavity spinneret for electrostatic-rotational jet spinning to obtain an interwoven fiber membrane drug-loaded dressing.

[0023] The following examples provide further details.

[0024] Example 1: PLA particles were added to a DCM / DMF binary solvent and stirred at room temperature until completely dissolved to prepare spinning solution A. The solution was then allowed to stand to remove bubbles before use. Silk fibroin and tetracycline were weighed, with the tetracycline accounting for 5% of the silk fibroin mass. Anhydrous formic acid was added as a solvent, and the solution was stirred at room temperature until completely dissolved to prepare spinning solution B. This solution was then allowed to stand to remove bubbles before use. Spinning solutions A and B were separately injected into a dual-cavity spinneret for electrostatic-rotary jet spinning. The ratio of PLA to natural polymer spinnerets was 1:4. The motor speed was set to 2500 rpm, and the voltage was set to 4 kV to obtain an interwoven fiber membrane drug-loaded dressing.

[0025] Test results: The average diameter of the silk fibroin drug-loaded fibers was 0.69±0.29 μm, and the average diameter of the PLA fibers was 10.07±1.26 μm, with a fiber ratio of approximately 9:1. The average pore size was 6.94 μm, and the porosity was 90.59±3.84%. The maximum tensile strength was 3.39 MPa, and the elongation at break was 32%. The dynamic contact angle was initially 114.67°, gradually decreasing to 107.83° within 300 s. The moisture permeability was 3892±88 g / (m²·24 h), the air permeability was 188 mm / s, and the liquid absorption was 18.03±1.66 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 245.61±7.41 g / min, respectively. -1 1294.331±16.37g min -1 and 4262.82±27.47 g min -1After 24 hours of incubation, the relative cell viability was 114.84±5.15%, and after 72 hours of incubation, the relative cell viability was 83.36±6.87%. The static drug release was 69.25±0.88%.

[0026] 1. Microscopic morphological characterization: The SEM image of the multifunctional micro / nano interwoven fiber membrane drug-loaded dressing prepared by the above method is shown below. Figure 2 As shown, SF / PCL / PVP fibers and PLA fibers exhibit a clear interweaving state, meaning that both types of fibers exist simultaneously in the same plane, and the fibers interweave and intertwine with each other, exhibiting a coarse-to-fine interweaving distribution. Furthermore, by statistically analyzing the PLA fiber content within the interwoven fiber membrane, it can be seen that when the spinneret ratio of SF / PCL / PVP spinning solution to PLA spinning solution is 1:4, the PLA fiber content in the prepared interwoven fiber membrane is 10±2.11%; therefore, the ratio of SF / PCL / PVP fibers to PLA fibers in the interwoven fiber membrane is approximately 9:1. When the spinneret configuration range is 1~4:4~1, the fiber ratio is 1~9:9~1.

[0027] Other embodiments of the prepared multifunctional micro-nano interwoven fiber membrane drug-loaded dressings have similar properties.

[0028] 2. Stress-strain curve: The stress-strain curve of the multifunctional micro / nano interwoven fiber membrane drug-loaded dressing prepared by the above method is shown in the figure. Figure 3 As shown, the maximum strength of the SF / PCL / PVP fiber membrane is 0.62 MPa, the maximum strength of the PLA fiber membrane is 2.15 MPa, while the maximum strengths of the SF / PCL / PVP-PLA interwoven fiber membranes (9:1, 8:2, and 7:3) are 3.21 MPa, 3.98 MPa, and 4.73 MPa, respectively. The results indicate that the SF / PCL / PVP fiber membrane has poor tensile strength, while the PLA fiber membrane has good strength. Therefore, PLA fibers can be used to reinforce SF / PCL / PVP fibers. When the PLA fiber content in the interwoven fiber membrane increases from 10% to 30%, the maximum strength of the SF / PCL / PVP-PLA interwoven fiber membrane increases by approximately 2.2 times compared to the PLA fiber membrane, and the elongation corresponding to the maximum strength increases from 10% to over 20%. This demonstrates that the interwoven structure can not only adjust the pore structure of the fiber membrane but also improve its mechanical properties.

[0029] Other embodiments of the prepared multifunctional micro-nano interwoven fiber membrane drug-loaded dressings have similar properties.

[0030] 3. Moisture permeability and liquid absorbency: The moisture permeability and liquid absorption curves of the multifunctional micro / nano interwoven fiber membrane drug-loaded dressing prepared by the above method are shown below. Figure 4 As shown. By Figure 4 As shown in section a, the WVTRs of SF / PCL / PVP fiber membrane, PLA fiber membrane, and SF / PCL / PVP-PLA interwoven fiber membrane (9:1, 8:2, and 7:3) are 834±67 g / (m²·24 h), 3892±88 g / (m²·24 h), 5100±141 g / (m²·24 h), 4821±101 g / (m²·24 h), and 4580±77 g / (m²·24 h), respectively. The results showed that the WVTR of the SF / PCL / PVP-PLA interwoven fiber membrane was higher than that of the PLA fiber membrane, and more than five times that of the SF / PCL / PVP fiber membrane. However, the WVTR of the interwoven fiber membrane decreased slightly with increasing PLA fiber content. Analysis revealed that the better hydrophilicity of SF / PCL / PVP fibers leads to swelling after moisture absorption, resulting in decreased porosity and consequently poorer permeability. In contrast, the strong hydrophobicity of the PLA fiber membrane resulted in better permeability for the interwoven fiber membrane. Furthermore, the WVTR decreased slightly with increasing hydrophobic PLA fiber content, making it suitable for moderate to severe exudative wounds. Figure 4 As shown in section b, the liquid absorption capacities of SF / PCL / PVP fiber membrane, PLA fiber membrane, and SF / PCL / PVP-PLA interwoven fiber membrane (9:1, 8:2, and 7:3) were 4.82 ± 0.55 g, respectively. -1 12.65±0.88 gg -1 18.03±1.66 gg -1 16.65±1.16 gg -1 and 15.19±1.36 gg -1 The results showed that as the PLA fiber content in the interwoven fiber membrane increased, the liquid absorption capacity of the interwoven fiber membrane decreased slightly, but remained higher than that of the SF / PCL / PVP fiber membrane and the PLA fiber membrane. Analysis indicates that the interwoven fiber membrane, with its larger pore size and apparent volume, provides sufficient space for the SF / PCL / PVP fibers to absorb water and expand, thus achieving high liquid absorption performance.

[0031] Other embodiments of the prepared multifunctional micro-nano interwoven fiber membrane drug-loaded dressings have similar properties.

[0032] 4. Relative cell viability: NIH3T3 cells were seeded onto SF / PCL / PVP-PLA interwoven fiber membranes and cultured. The cytotoxicity of the interwoven fiber membranes was analyzed using the CCK-8 assay, and live / dead cell staining imaging was performed. The relative cell viability of the multifunctional micro / nano interwoven fiber membrane drug-loaded dressing prepared by the above method was as follows: Figure 5As shown, after 24 h of incubation, the relative cell viability of NIH3T3 cells cultured with SF / PCL / PVPPLA interwoven fiber membranes (9:1, 8:2, and 7:3) with different PLA fiber contents were 114.84±5.15%, 110.57±4.7%, and 99.77±1.51%, respectively; after 72 h of incubation, the relative cell viability were 83.36±6.87%, 82.82±8.3%, and 81.34±8.42%, respectively. The results indicate that after 24 h of incubation, direct contact culture of NIH3T3 cells did not exhibit cytotoxicity, and the release of some free amino acids from SF increased the concentration of amino acids required for cell survival, promoting the growth of NIH3T3 cells. This suggests that SF-based interwoven fiber membranes possess excellent cell compatibility. Meanwhile, higher PLA content slightly reduced relative cell viability, indicating that hydrophobic PLA fibers affect the release of free amino acids. Lower PLA fiber content promotes free amino acid release, while higher PLA fiber content slows down the release. After 72 hours of incubation, relative cell viability remained above 80%, and there was no significant difference in cell viability among the three interwoven fiber membrane experimental groups, indicating that the amount of free amino acids released from the fibers was essentially the same after 72 hours. It is worth noting that the growth of the NIH3T3 cell line was inhibited by contact. If it can maintain high cell viability after direct contact culture with the SF-based interwoven fiber membrane, it further demonstrates the excellent biocompatibility of the SF-based interwoven fiber membrane.

[0033] 5. Static cumulative drug release curve: The static cumulative drug release curve of the multifunctional micro / nano interwoven fiber membrane drug-loaded dressing prepared by the above method is shown in the figure. Figure 6 As shown. Figure 6As shown in Figure 1a, the initial release rates of TCH@SF / PCL / PVP fiber membrane, IBU@SF / PCL / PVP fiber membrane, and CUR@SF / PCL / PVP fiber membrane in their respective buffer solutions within 1 h were 37.89±2.59%, 34.81±4.64%, and 23.54±3.22%, respectively, and their cumulative release rates within 110 h were 81.6±0.85%, 72.46±0.58%, and 76.25±0.6%, respectively. Meanwhile, the initial release rates of TCH@SF / PCL / PVP-PLA interwoven fiber membrane, IBU@SF / PCL / PVP-PLA interwoven fiber membrane, and CUR@SF / PCL / PVP-PLA interwoven fiber membrane in their respective buffer solutions within 1 h were 13.96±1.59%, 21.75±3.98%, and 17.25±3.88%, respectively, and their cumulative release rates within 110 h were 81.6±0.85%, 72.46±0.58%, and 76.25±0.6%, respectively. The cumulative release rates were 69.25±0.88%, 58.04±2.01%, and 62.58±0.74%, respectively. The results indicate that interweaving hydrophobic PLA fibers with drug-loaded fibers significantly prolongs drug release time. Analysis shows that hydrophobic substances can prolong drug release, and simultaneously, PLA fibers increase the transfer and diffusion pathways of drug molecules, which helps alleviate burst release and prolong release time.

[0034] Other embodiments of the prepared multifunctional micro-nano interwoven fiber membrane drug-loaded dressings have similar properties.

[0035] Example 2: The rest is the same as in Example 1, except that sodium alginate is used as the carrier, ibuprofen is used as the drug, accounting for 10% of the mass of sodium alginate, and anhydrous acetic acid is used as the solvent; the spinneret configuration is 4:1, the motor speed is 3500 rpm, and the voltage is 10 kV.

[0036] Test results: The average diameter of the sodium alginate-loaded fibers was 1.1 μm, and the average diameter of the PLA fibers was 20.09±1.21 μm, with a fiber ratio of approximately 1:9. The average pore size was 27.31 μm, and the porosity was 88.53±2.77%. The maximum tensile strength was 9.8 MPa, and the elongation at break was 28%. The initial dynamic contact angle was 127.98°, gradually decreasing to 108.13° within 300 s. The moisture permeability was 1080±8.88 g / (m²·24 h), the air permeability was 105 mm / s, and the liquid absorption was 11.55±1.32 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 411.96±6.11 g / min, respectively. -1 1810.1±20 g min -1 and 4690.58±33.47 g min -1After 24 h of incubation, the relative cell viability was 108.84 ± 4.43%, and after 72 h of incubation, the relative cell viability was 85.84 ± 4.19%. The static drug release was 57.31 ± 1.21%; at a flow rate of 1 m / s... -1 3 m s⁻¹, 6 ms⁻¹ and 9 m·s -1 The times required for the cumulative dynamic drug release to reach approximately 80% were 16 h, 9 h, 5.25 h, and 3.5 h, respectively.

[0037] The multifunctional micro / nano interwoven fiber membrane drug-loaded dressing prepared by the above method has the following water permeability: Figure 7 As shown, by Figure 7 As shown in section a, when the water pressure is 1 kPa, the water flux of the PLA fiber membrane and the SF / PCL / PVP-PLA interwoven fiber membrane (9:1, 8:2, and 7:3) are 314.14 ± 1.97 g / min. -1 311.96±6.11 g min -1 125 309.11±3.47 g min -1 and 302.64±4.79 g min -1 .Depend on Figure 7 As shown in b, when the water pressure is 3 kPa, the water flux of the PLA fiber membrane and the SF / PCL / PVP-PLA interwoven fiber membrane (9:1, 8:2, and 7:3) are 1376.65 ± 15.56 g / min, respectively. -1 1310.1±20 gmin -1 1264.35±15.21 g min -1 and 1232.08±28.89 g min -1 .Depend on Figure 7 As shown in Figure c, when the water pressure is 5 kPa, the water flux of PLA fiber membrane and SF / PCL / PVPPLA interwoven fiber membrane (9:1, 8:2, and 7:3) are 4504.05 ± 26.78 g / min. -1 449.58±33.47 g min -1 4366.66±44.45 g min -1 and 4220±48.45 g min -1 The results show that the interwoven fiber membrane has high water flux, indicating its excellent water permeability. In summary, the water flux of the interwoven fiber membrane decreases slightly with increasing PLA fiber content.

[0038] Other embodiments of the prepared multifunctional micro-nano interwoven fiber membrane drug-loaded dressings have similar properties.

[0039] The dynamic cumulative drug release curve of the multifunctional micro / nano interwoven fiber membrane drug-loaded dressing prepared by the above method is shown in the figure below. Figure 8 As shown, V PBS =1 ms -1 At that time, the cumulative release rates of IBU@SF / PCL / PVP-PLA interwoven fiber membranes (9:1, 8:2, and 7:3) within 24 h were 82.45±1.86%, 78.56±1.79%, and 73.66±2.12%, respectively; V PBS =3 ms -1 At that time, the cumulative release rates of IBU@SF / PCL / PVP-PLA interwoven fiber membranes (9:1, 8:2, and 7:3) within 16 h were 86.33±0.94%, 83.27±1.48%, and 79.86±1.49%, respectively; V PBS =6 ms -1 At that time, the cumulative release rates of IBU@SF / PCL / PVP-PLA interwoven fiber membranes (9:1, 8:2, and 7:3) within 10 h were 88.12±1.57%, 84.88±1.86%, and 80.41±1.56%, respectively; V PBS =9 ms -1 At 6 h, the cumulative drug release rates of IBU@SF / PCL / PVP-PLA interwoven fiber membranes (9:1, 8:2, and 7:3) were 91.02±0.88%, 86.33±1.45%, and 82.75±1.73%, respectively. The results indicate that with increasing buffer flow rate, the cumulative drug release rate continuously increases, while the total release time rapidly decreases; simultaneously, higher PLA fiber content slightly reduces drug release. Analysis suggests that fluid flow can cause drastic changes in the concentration gradient of released drug around the drug-loaded fibers, thereby accelerating drug release. Furthermore, higher PLA fiber content increases the likelihood of downstream IBU@SF / PCL / PVP fibers being covered, preventing some drug release and leading to a decrease in drug release rate.

[0040] Other embodiments of the prepared multifunctional micro-nano interwoven fiber membrane drug-loaded dressings have similar properties.

[0041] Example 3: The rest is the same as in Example 1, except that chitosan is used as the carrier, curcumin (5% by mass) is used as the drug, hexafluoroisopropanol is used as the solvent, the spinneret configuration is 1:1, the motor speed is 3000 rpm, and the voltage is 9 kV.

[0042] Test results: The average diameter of chitosan-loaded fibers was 0.91±0.17 μm, and the average diameter of PLA fibers was 50.14±1.19 μm, with a fiber ratio of approximately 9:4. The average pore size was 49.37 μm, and the porosity was 84.12±3.08%. The maximum tensile strength was 7.73 MPa, and the elongation at break was 26%. The dynamic contact angle was initially 99.34°, gradually decreasing to 72.51° within 300 s. The moisture permeability was 3120±72 g / (m²·24 h), the air permeability was 142 mm / s, and the liquid absorption was 16.05±1.53 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 290.43±6.12 g / min, respectively. -1 1295.67±19.35 g min -1 and 4451.28±31.64 g min -1 After 24 h of incubation, the relative cell viability was 113.28 ± 4.91%, and after 72 h of incubation, the relative cell viability was 83.04 ± 5.88%. The static drug release was 67.12 ± 0.97%.

[0043] Example 4: The rest is the same as in Example 1, except that collagen is used as a carrier to load the polypeptide ε-polylysine (1% by mass), the solvent is anhydrous formic acid, the spinneret configuration is 2:3, the motor speed is 2700 rpm, and the voltage is 7 kV.

[0044] Test results: The average diameter of collagen-loaded fibers was 0.48±0.11 μm, and the average diameter of PLA fibers was 10.04±1.22 μm, with a fiber ratio of approximately 3:2. The average pore size was 8.89 μm, and the porosity was 87.36±2.94%. The maximum tensile strength was 3.92 MPa, and the elongation at break was 38%. The dynamic contact angle was initially 96.15°, gradually decreasing to 64.87° within 300 s. The moisture permeability was 3510±79 g / (m²·24 h), the air permeability was 165 mm / s, and the liquid absorption was 18.77±1.64 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 303.21±5.88 g / min, respectively. -1 1318.43±20.17 gmin -1 and 4553.62±35.29 g min -1 After 24 h of incubation, the relative cell viability was 116.74 ± 5.25%, and after 72 h of incubation, the relative cell viability was 86.51 ± 4.93%. The static drug release was 73.45 ± 1.16%.

[0045] Example 5: The rest is the same as in Example 1, except that zein is used as a carrier to load antimicrobial peptides (10% by mass), and anhydrous acetic acid is used as the solvent; the spinneret configuration is 3:2, the motor speed is 3300 rpm, and the voltage is 8 kV.

[0046] Test results: The average diameter of the zein-loaded fibers was 1.53±0.26 μm, and the average diameter of the PLA fibers was 10.11±1.24 μm, with a fiber ratio of approximately 17:5. The average pore size was 7.18 μm, and the porosity was 68.27±2.85%. The maximum tensile strength was 7.44 MPa, and the elongation at break was 22%. The dynamic contact angle was initially 112.36°, gradually decreasing to 103.28° within 300 s. The moisture permeability was 4860±45 g / (m²·24 h), the air permeability was 87 mm / s, and the liquid absorption was 11.93±1.28 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 267.85±6.74 g / min, respectively. -1 1278.52±18.93 gmin -1 and 4367.44±28.56 g min -1 After 24 h of incubation, the relative cell viability was 109.92 ± 4.67%, and after 72 h of incubation, the relative cell viability was 84.35 ± 5.12%. The static drug release was 65.73 ± 1.08%.

[0047] Example 6: The rest is the same as in Example 1, except that gelatin is used as a carrier to load thrombin (0.001% by mass), and hexafluoroisopropanol is used as the solvent; the spinneret configuration is 1:3, the motor speed is 2600 rpm, and the voltage is 8 kV.

[0048] Results: The average diameter of the gelatin-loaded fibers was 0.53±0.09 μm, and the average diameter of the PLA fibers was 10.08±1.18 μm, with a fiber ratio of approximately 3:4. The average pore size was 8.76 μm, and the porosity was 81.95±3.17%. The maximum tensile strength was 2.88 MPa, and the elongation at break was 45%. The dynamic contact angle was initially 91.62°, gradually decreasing to 58.74° within 300 s. The moisture permeability was 3280±68 g / (m²·24 h), the air permeability was 158 mm / s, and the liquid absorption was 19.42±1.75 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 296.78±6.35 g / min, respectively. -1 1305.84±19.72 g min -1 and 4487.93±33.41 g min -1After 24 h of incubation, the relative cell viability was 118.53 ± 5.48%, and after 72 h of incubation, the relative cell viability was 78.12 ± 5.69%. The static drug release was 75.89 ± 1.24%.

[0049] Example 7: The rest is the same as in Example 1, except that lotus seed starch is used as the carrier to load epidermal growth factor (1% by mass), and anhydrous formic acid is used as the solvent; the spinneret configuration is 3:1, the motor speed is 3400 rpm, and the voltage is 10 kV.

[0050] Test results: The average diameter of the lotus seed starch-loaded fibers was 4.87±0.41 μm, and the average diameter of the PLA fibers was 10.19±1.27 μm, with a fiber ratio of approximately 27:4. The average pore size was 16.53 μm, and the porosity was 73.18±2.92%. The maximum tensile strength was 2.15 MPa, and the elongation at break was 19%. The dynamic contact angle was initially 94.75°, gradually decreasing to 69.33° within 300 s. The moisture permeability was 1520±38 g / (m²·24 h), the air permeability was 62 mm / s, and the liquid absorption was 11.08±1.19 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 253.94±7.03 g / min, respectively. -1 1267.19±17.88 gmin -1 and 4312.76±29.15 g min -1 After 24 h of incubation, the relative cell viability was 115.39 ± 5.11%, and after 72 h of incubation, the relative cell viability was 85.93 ± 5.34%. The static drug release was 71.63 ± 1.09%.

[0051] Example 8: The rest is the same as in Example 1, except that hyaluronic acid is used as the carrier to load the antibiotic vancomycin (20% by mass), and anhydrous acetic acid is used as the solvent; the spinneret configuration is 1:2, the motor speed is 2800 rpm, and the voltage is 6 kV.

[0052] Test results: The average diameter of the hyaluronic acid-loaded fibers was 3.42±0.53 μm, and the average diameter of the PLA fibers was 10.05±1.15 μm, with a fiber ratio of approximately 9:8. The average pore size was 7.94 μm, and the porosity was 77.84±3.35%. The maximum tensile strength was 3.56 MPa, and the elongation at break was 24%. The dynamic contact angle was initially 86.79°, gradually decreasing to 51.46° within 300 s. The moisture permeability was 1270±42 g / (m²·24 h), the air permeability was 50 mm / s, and the liquid absorption was 16.84±1.47 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 239.67±7.58 g / min, respectively. -1 1260.91±21.04 gmin -1 and 4248.35±30.72 g min -1 After 24 h of incubation, the relative cell viability was 104.61 ± 4.82%, and after 72 h of incubation, the relative cell viability was 79.85 ± 5.57%. The static drug release was 63.57 ± 1.31%.

[0053] Example 9: The rest is the same as in Example 1, except that cellulose is used as the carrier, diclofenac (1% by mass) is loaded, and hexafluoroisopropanol is used as the solvent; the spinneret configuration is 4:1, the motor speed is 3200 rpm, and the voltage is 4 kV.

[0054] Test results: The average diameter of the cellulose drug-loaded fibers was 0.74±0.13 μm, and the average diameter of the PLA fibers was 10.22±1.29 μm, with a fiber ratio of approximately 9:1. The average pore size was 19.06 μm, and the porosity was 89.45±2.76%. The maximum tensile strength was 6.38 MPa, and the elongation at break was 18%. The dynamic contact angle was initially 101.88°, gradually decreasing to 74.63° within 300 s. The moisture permeability was 3710±81 g / (m²·24 h), the air permeability was 179 mm / s, and the liquid absorption was 18.59±1.82 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 314.82±5.97 g / min, respectively. -1 1332.45±21.63 g min -1 and 4618.74±37.25 g min -1 After 24 h of incubation, the relative cell viability was 110.47 ± 4.59%, and after 72 h of incubation, the relative cell viability was 84.92 ± 5.26%. The static drug release was 66.34 ± 0.92%.

[0055] Example 10: The rest is the same as in Example 1, except that pectin / silk fibroin is used as the carrier, natural polyphenol shikonin (10% by mass) is loaded, anhydrous formic acid is used as the solvent, the spinneret is configured as 1:1, the motor speed is 3000 rpm, and the voltage is 9 kV.

[0056] Test results: The average diameter of the pectin / silk fibroin-loaded fibers was 1.78±0.29 μm, and the average diameter of the PLA fibers was 10.13±1.23 μm, with a fiber ratio of approximately 9:4. The average pore size was 8.65 μm, and the porosity was 72.91±3.14%. The maximum tensile strength was 5.67 MPa, and the elongation at break was 29%. The dynamic contact angle was initially 97.53°, gradually decreasing to 67.28° within 300 s. The moisture permeability was 2240±56 g / (m²·24 h), the air permeability was 105 mm / s, and the liquid absorption was 14.32±1.38 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 278.16±6.49 g / min, respectively. -1 1287.03±19.84 gmin -1 and 4419.55±32.18 g min -1 After 24 h of incubation, the relative cell viability was 111.86 ± 4.75%, and after 72 h of incubation, the relative cell viability was 85.27 ± 5.08%. The static drug release was 68.99 ± 1.12%.

[0057] Example 11: The rest is the same as in Example 1, except that agarose / gelatin is used as the carrier to load natural polyphenol quercetin (1% by mass), and anhydrous acetic acid is used as the solvent; the spinneret configuration is 2:1, the motor speed is 2500 rpm, and the voltage is 10 kV.

[0058] Test results: The average diameter of the agarose / gelatin-loaded fibers was 2.12±0.34 μm, and the average diameter of the PLA fibers was 10.03±1.17 μm, with a fiber ratio of approximately 9:2. The average pore size was 7.43 μm, and the porosity was 65.79±3.26%. The maximum tensile strength was 6.14 MPa, and the elongation at break was 31%. The dynamic contact angle was initially 100.27°, gradually decreasing to 71.85° within 300 s. The moisture permeability was 1740±48 g / (m²·24 h), the air permeability was 79 mm / s, and the liquid absorption was 12.67±1.21 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 261.35±7.21 g / min, respectively. -1 1274.88±18.56 gmin -1 and 4345.67±29.88 g min-1 After 24 h of incubation, the relative cell viability was 114.19 ± 5.33%, and after 72 h of incubation, the relative cell viability was 86.09 ± 5.45%. The static drug release was 64.48 ± 1.03%.

[0059] Example 12: The rest is the same as in Example 1, except that gelatin is used as the carrier to load thrombin (1% by mass), and anhydrous acetic acid / water solution is used as the solvent; the spinneret configuration is 1:4, the motor speed is 3500 rpm, and the voltage is 6 kV.

[0060] Test results: The average diameter of the gelatin-loaded fibers was 1.05±0.18 μm, and the average diameter of the PLA fibers was 10.18±1.25 μm, with a fiber ratio of approximately 9:16. The average pore size was 7.82 μm, and the porosity was 74.55±3.09%. The maximum tensile strength was 3.24 MPa, and the elongation at break was 42%. The dynamic contact angle was initially 93.44°, gradually decreasing to 61.35° within 300 s. The moisture permeability was 2860±63 g / (m²·24 h), the air permeability was 126 mm / s, and the liquid absorption was 17.91±1.56 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 285.69±6.83 g / min, respectively. -1 1299.52±20.45 g min -1 and 4511.36±34.72 g min -1 After 24 h of incubation, the relative cell viability was 117.08 ± 5.17%, and after 72 h of incubation, the relative cell viability was 87.42 ± 5.93%. The static drug release was 74.26 ± 1.17%.

[0061] Example 13: The rest is the same as in Example 1, except that zein / silk fibroin is used as the carrier, naproxen (5% by mass) is loaded, and hexafluoroisopropanol is used as the solvent; the spinneret configuration is 1:1, the motor speed is 3000 rpm, and the voltage is 9 kV.

[0062] Test results: The average diameter of the zein / silk fibroin-loaded fibers was 1.21±0.22 μm, and the average diameter of the PLA fibers was 10.16±1.21 μm, with a fiber ratio of approximately 9:4. The average pore size was 15.94 μm, and the porosity was 81.36±3.02%. The maximum tensile strength was 4.88 MPa, and the elongation at break was 24%. The dynamic contact angle was initially 110.58°, gradually decreasing to 101.62° within 300 s. The moisture permeability was 2050±51 g / (m²·24 h), the air permeability was 94 mm / s, and the liquid absorption was 14.08±1.31 g / g. Under water pressures of 1 kPa, 3 kPa, and 5 kPa, the water flux was 271.44±6.58 g / min, respectively. -1 1281.19±19.27 g min -1 and 4382±30.64 g min -1 After 24 h of incubation, the relative cell viability was 108.75 ± 4.88%, and after 72 h of incubation, the relative cell viability was 83.68 ± 5.24%. The static drug release was 66.01 ± 0.99%.

[0063] The above embodiments are preferred implementations of the present invention. In addition, the present invention can be implemented in other ways. Any obvious substitutions without departing from the concept of the present technical solution are within the protection scope of the present invention.

[0064] To facilitate understanding by those skilled in the art of the improvements of this invention over the prior art, some of the accompanying drawings and descriptions have been simplified, and for clarity, some other elements have been omitted from this application. Those skilled in the art should realize that these omitted elements may also constitute the content of this invention.

Claims

1. A method for preparing a multifunctional micro / nano interwoven fiber membrane drug-loaded dressing, characterized in that, Includes the following steps: S1. Add PLA particles to a binary solvent of DCM and DMF, with a volume ratio of DCM to DMF of 9:

1. Stir at room temperature until completely dissolved to prepare spinning solution A. Let stand to remove bubbles before use. S2. Weigh the natural polymeric drug-carrying material and the active drug, add solvent, stir at room temperature until completely dissolved, prepare spinning solution B, and let stand to remove bubbles before use; S3. The spinning solution A described in S1 and the spinning solution B described in S2 are respectively injected into a dual-cavity spinneret for electrostatic-rotational jet spinning to obtain an interwoven fiber membrane drug-loaded dressing.

2. The preparation method according to claim 1, characterized in that, The natural polymeric drug-carrying material described in S2 includes protein-based polymers and polysaccharide polymers; the protein-based polymers are selected from one or more of silk fibroin, collagen, gelatin and zein; the polysaccharide polymers are selected from one or more of lotus seed starch, sodium alginate, chitosan, cellulose, hyaluronic acid, pectin, agarose, dextran, xanthan gum, heparin and cyclodextrin.

3. The preparation method according to claim 1, characterized in that, The active drug described in S2 is one or more of the following: antibiotics, nonsteroidal anti-inflammatory drugs, natural polyphenolic compounds, polypeptides, and hemostatic agents; The antibiotic is one or more of tetracycline, levofloxacin, and vancomycin; the nonsteroidal anti-inflammatory drug is one or more of ibuprofen, naproxen, and diclofenac. The natural polyphenolic compounds are one or more of lotus polyphenols, curcumin, quercetin, resveratrol, and shikonin; The polypeptide is one or more of ε-polylysine, antimicrobial peptide, thrombin, and epidermal growth factor.

4. The preparation method according to claim 1, characterized in that, The solvent mentioned in S2 is one or more of anhydrous formic acid, anhydrous acetic acid, and hexafluoroisopropanol.

5. The preparation method according to claim 3, characterized in that, The antibiotics in S2 have a mass ratio of 5% to 20%; the nonsteroidal anti-inflammatory drugs have a mass ratio of 1% to 10%; the natural polyphenols have a mass ratio of 1% to 10%; when the polypeptide is ε-polylysine or an antimicrobial peptide, its mass ratio is 1% to 10%; when the polypeptide is thrombin or epidermal growth factor, its mass ratio is 0.001% to 1%.

6. The preparation method according to claim 1, characterized in that, The spinneret of the dual-chamber spinneret described in S3 has a spinneret configuration of 1~4:4~1; the motor speed is 2500~3500 rpm and the voltage is 4~10 kV.

7. A multifunctional micro / nano interwoven fiber membrane drug-loaded dressing, based on the preparation method according to any one of claims 1-6, characterized in that, The natural polymer fibers have a diameter of 0.5~5 μm, the PLA fibers have a diameter of 5~20 μm, the fiber ratio is 1~9:9~1, the porosity is 60%~90%, the dressing has a moisture permeability of 1000~5000 g / (m²·24 h), an air permeability of 50~200 mm / s, a tensile strength of 1~10 MPa, a liquid absorbency of 10~20 g / g, and a cell activity of 70%~120%.

Images