Preparation method of drug-loaded aerogel wound dressing with controllable drug release process

Abstract

This invention provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release. A pre-crosslinked solution comprising a polymer nanofiber suspension, sodium alginate solution, polyethyleneimine aqueous solution, and a crosslinking agent is pre-formed using a molding or spraying method, followed by freeze-drying to obtain a sodium alginate-based aerogel. This aerogel is then reacted in a calcium chloride solution to obtain a drug-loadable aerogel, which is finally loaded with drug to obtain the drug-loaded aerogel wound dressing with controllable drug release. This invention achieves control over the drug release process by adjusting the aerogel forming method and freeze-drying parameters to modify the aerogel structure. Through a pre-crosslinking-freeze-drying-re-crosslinking process, an aerogel with high drug loading capacity, dimensional stability, and good mechanical properties is obtained. This aerogel can be applied to acute and chronic wounds with different recovery needs, continuously controlling the drug release process to prevent wound infection and accelerate recovery, and has broad market prospects.

Description

Technical Field

[0001] This invention relates to the field of drug-loaded dressing preparation technology, and in particular to a method for preparing a drug-loaded aerogel wound dressing with a controllable drug release process. Background Technology

[0002] Traditional medical dressings, such as cotton balls, gauze, or bandages, can absorb wound exudate to varying degrees and offer some protection to the wound. However, these dressings are only temporary coverings and do not heal the wound. An ideal wound dressing should be conducive to the wound healing process, non-toxic, biodegradable, and possess excellent mechanical and biological properties. The dressing needs to absorb excess exudate and blood to protect the wound from secondary infection, while maintaining appropriate humidity and temperature. It should also prevent bacterial infection and excessive moisture loss, providing a moist and clean environment for the wound.

[0003] Currently, gel materials possess excellent physicochemical and biological properties and are widely used in wound dressings. Hydrogels, rich in hydrophilic groups, can absorb water and swell under physiological conditions, exhibiting characteristics of both solid and liquid phases, and are often used in dressings. However, hydrogels swell rapidly upon contact with water and store the absorbed water. The presence of a large amount of water can affect their subsequent hygroscopicity, making them unsuitable for wounds with significant exudate. They can also affect the material's breathability, which is detrimental to wound healing when used in wound dressings.

[0004] Aerogels are nanoscale porous solid materials formed by replacing the liquid phase in a gel with gas through a sol-gel method and a specific drying process. Aerogels are characterized by high porosity and low density, making them suitable for loading drugs to prepare drug-loaded aerogel dressings. Existing aerogel dressings are mostly prepared using sodium alginate. For example, a patent (application number CN202011205566.X) discloses a method for preparing a multifunctional aerogel dressing that promotes wound healing. This method involves heating amino acid derivatives, antibacterial peptide derivatives, and natural polysaccharides (sodium alginate) to obtain a clear solution, then freezing the solution to obtain a hydrogel, and finally freeze-drying the hydrogel to produce a multifunctional aerogel dressing. This method incorporates antibacterial substances into the raw materials, providing antibacterial effects during application. However, its antibacterial effect is limited by the content of the raw materials, making it difficult to achieve long-term antibacterial effects and unsuitable for wounds with slow healing. Furthermore, the poor cross-linking of the raw materials during preparation results in dimensional instability and poor mechanical properties in the final aerogel, limiting its applications. In addition, there is little research on the drug release process of drug-loaded aerogel dressings in the existing technology, while the control of the drug release process is of great significance for wound healing.

[0005] In view of this, it is necessary to design an improved method for preparing drug-loaded aerogel wound dressings with controllable drug release process in order to solve the above problems. Summary of the Invention

[0006] The purpose of this invention is to provide a method for preparing a drug-loaded aerogel wound dressing with controllable drug release. By adjusting the aerogel molding method and freeze-drying parameters, the structure of the aerogel is changed, thereby achieving control over the drug release process. Through a pre-crosslinking-freeze-drying-re-crosslinking process, a drug-loaded aerogel with large drug loading capacity, dimensional stability, good mechanical properties, and controllable drug release is obtained. When this aerogel is applied to wound dressings, it can continuously control the drug release process, prevent bacterial infection of the wound, accelerate wound healing, and has excellent performance and broad market prospects.

[0007] To achieve the above-mentioned objectives, this invention provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release, comprising the following steps:

[0008] S1. A pre-crosslinking solution containing polymer nanofiber suspension, sodium alginate solution, polyethyleneimine aqueous solution and crosslinking agent is pre-formed by molding or spraying, and then frozen at -20℃ to -80℃. After being taken out, it is freeze-dried for 12 to 48 hours to obtain sodium alginate-based aerogel.

[0009] The thickness of the sodium alginate-based aerogel obtained by the mold method is 1-10 cm; the spraying method involves high-pressure spraying of the pre-crosslinked solution onto a substrate, the substrate having a porosity of 30%-50% and a pore size of 9-15 μm, to obtain the sodium alginate-based aerogel with a thickness of 0.5-2.5 mm.

[0010] S2. The sodium alginate-based aerogel obtained in step S1 is placed in a calcium chloride solution with a mass fraction of 5% to 10% and reacted for 12 to 24 hours to obtain a drug-loadable aerogel.

[0011] S3. Immerse the drug-loadable aerogel described in step S2 in a drug aqueous solution, allow it to adsorb for a certain period of time, and then freeze-dry it to obtain a drug-loadable aerogel wound dressing with a controllable drug release process.

[0012] As a further improvement of the present invention, in step S1, the mass ratio of the polymer nanofibers, sodium alginate and polyethyleneimine in the pre-crosslinked solution is 1:(1.1-1.2):(0.2-0.4), and the preferred mass ratio is 1:1:0.3.

[0013] As a further improvement of the present invention, the polymer nanofibers are PVA-co-PE nanofibers, the molecular weight of the polyethyleneimine is 10,000 to 60,000, and the crosslinking agent is a polyaldehyde; the amount of the crosslinking agent added is 0.25% to 0.6% of the volume of the PVA-co-PE nanofiber suspension.

[0014] As a further improvement of the present invention, the sodium alginate-based aerogel prepared by the mold method has a through-pore structure with an average pore size of 6-10 μm; the sodium alginate-based aerogel prepared by the spraying method has a uniform circular pore structure with an average pore size of 10-20 μm.

[0015] As a further improvement of the present invention, in step S1, the surface of the sodium alginate-based aerogel prepared by the mold method is further coated with the pre-crosslinked solution under high pressure, and then freeze-dried again for 12-36 hours to obtain a sodium alginate-based aerogel with an irregular internal pore structure.

[0016] As a further improvement of the present invention, the alginate-based aerogel with the irregular structure includes a double-layer pore structure, wherein the bottom layer is a vertically arranged pore structure layer and the upper layer is a circular pore structure layer composite with the pore structure layer.

[0017] As a further improvement of the present invention, in step S1, the preparation of the pre-crosslinked solution includes the following steps:

[0018] S1. Prepare a polymer nanofiber suspension and add a crosslinking agent solution to obtain reaction solution I; the concentration of the polymer nanofiber suspension is 0.01-0.05 g / mL;

[0019] S2. Add sodium alginate solution to reaction solution I obtained in step S1 under stirring, and continue stirring for 2-4 hours to obtain reaction solution II;

[0020] S3. Add the polyethyleneimine aqueous solution to the reaction solution II described in step S2, and stir for 1.5 to 3 hours to obtain the pre-crosslinked solution.

[0021] As a further improvement of the present invention, in step S2, the concentration of the sodium alginate solution is 0.01 to 0.05 g / mL; in step S3, the mass fraction of polyethyleneimine in the polyethyleneimine aqueous solution is 1% to 10%, preferably 4% to 7%.

[0022] As a further improvement of the present invention, in step S1, the concentration of the crosslinking agent solution is 2.5% to 7%, preferably 5%.

[0023] As a further improvement of the present invention, in step S1, the preparation method of the polymer nanofiber suspension is as follows: polymer nanofibers are dispersed in a mixed solution of water and isopropanol, and centrifuged at a speed of 8000-10000 rpm for 10 min to obtain polymer nanofiber powder; the polymer nanofiber powder is placed in deionized water to obtain the polymer nanofiber suspension; the volume ratio of water to isopropanol in the mixed solution is (0.5-2):1.

[0024] The beneficial effects of this invention are:

[0025] 1. A method for preparing a drug-loaded aerogel wound dressing with controllable drug release, comprising: first, pre-forming a pre-crosslinking solution containing polymer nanofiber suspension, sodium alginate solution, polyethyleneimine aqueous solution, and a crosslinking agent using a mold method or spraying method, and then freezing it completely at -20℃ to -80℃, followed by freeze-drying to obtain sodium alginate-based aerogel; then, further crosslinking the sodium alginate-based aerogel in calcium chloride solution to obtain a drug-loaded aerogel; finally, immersing the drug-loaded aerogel in a drug aqueous solution, allowing it to adsorb for a certain period of time, and then freeze-drying to obtain a drug-loaded aerogel wound dressing with controllable drug release. This method, through a pre-crosslinking-freeze-drying-re-crosslinking process, produces a drug-loaded aerogel with large drug loading capacity, dimensional stability, good mechanical properties, and controllable drug release. When applied to wound dressings, this aerogel can continuously control the drug release process, prevent bacterial infection of the wound, accelerate wound healing, and has excellent performance and broad market prospects.

[0026] 2. This invention utilizes a molding method to prepare sodium alginate-based aerogels with a long, regularly arranged perforated channel structure. When loaded with drugs and used as wound dressings, the uniform and oriented perforated channels allow for controlled, long-term, and uniform drug release, aiding in the care of slowly healing wounds. By controlling the aerogel thickness, the total drug release time can be adjusted, enabling targeted treatment of wounds at different stages of recovery. Furthermore, the surface of the aerogel prepared by the molding method is further coated with a pre-crosslinking solution and then freeze-dried again to obtain a sodium alginate-based aerogel with an irregular internal pore structure. When used as a drug-loaded aerogel dressing, the surface circular pores allow for a large, short-term release of the drug for emergency wound treatment, while the vertically arranged channels at the bottom control a slow, long-term drug release, promoting subsequent wound healing. The thin-film sodium alginate-based aerogel prepared by the spraying method has a uniform internal circular pore structure, resulting in high drug release efficiency and making it suitable for wounds that heal in a relatively short time. Thus, by preparing aerogels with different structures, the drug release process can be controlled, filling the technological gap in this area and having significant implications for the development of drug-loaded aerogel wound dressings.

[0027] 3. This invention employs a pre-crosslinking-freeze-drying-re-crosslinking process. First, PVA-co-PE nanofibers and sodium alginate are crosslinked. Then, polyethyleneimine is added to form a crosslinked network structure of PVA-co-PE nanofibers, sodium alginate, and polyethyleneimine. The PVA-co-PE nanofibers act as a framework, while polyethyleneimine increases the degree of crosslinking between sodium alginate particles and between sodium alginate and PVA-co-PE nanofibers, thereby improving the mechanical properties of the aerogel and its hydrophilicity. The freeze-dried sodium alginate-based aerogel is then immersed in calcium chloride for further crosslinking, forming calcium ion crosslinks on its surface to obtain calcium alginate. This increases the degree of crosslinking, resulting in an aerogel with a composite structure, further enhancing its structural stability and mechanical strength, making it better suited to the practical needs of wound dressings. Attached Figure Description

[0028] Figure 1 This is a cross-sectional electron microscope image of the drug-loaded aerogel wound dressing containing lysozyme prepared in Example 1 of the present invention.

[0029] Figure 2 The image shows a surface electron microscope image of the drug-loaded aerogel wound dressing containing lysozyme prepared in Example 1 of this invention.

[0030] Figure 3 This diagram illustrates the lysozyme release process of the drug-loaded aerogel wound dressing prepared in Example 1 of this invention.

[0031] Figure 4 The image shows an infrared image of the drug-loaded aerogel wound dressing containing lysozyme prepared in Example 1 of this invention.

[0032] Figure 5 This is a cross-sectional electron microscope image of the drug-loaded aerogel wound dressing containing lysozyme prepared in Example 2 of the present invention.

[0033] Figure 6 The image shows a surface electron microscope (SEM) image of the drug-loaded aerogel wound dressing containing lysozyme prepared in Example 2 of this invention.

[0034] Figure 7 This diagram illustrates the lysozyme release process of the drug-loaded aerogel wound dressing prepared in Example 2 of the present invention.

[0035] Figure 8 This diagram illustrates the lysozyme release process of the drug-loaded aerogel wound dressing prepared in Example 3 of the present invention. Detailed Implementation

[0036] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be described in detail below with reference to the accompanying drawings and specific embodiments.

[0037] It should also be noted that, in order to avoid obscuring the present invention with unnecessary details, only the structures and / or processing steps closely related to the present invention are shown in the accompanying drawings, while other details that are not closely related to the present invention are omitted.

[0038] Additionally, it should be noted that the terms “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0039] A method for preparing a drug-loaded aerogel wound dressing with controllable drug release process includes the following steps:

[0040] S1. A pre-crosslinking solution containing polymer nanofiber suspension, sodium alginate solution, polyethyleneimine aqueous solution and crosslinking agent is pre-formed by molding or spraying, and then frozen at -20℃ to -80℃. After being taken out, it is freeze-dried for 12 to 48 hours to obtain sodium alginate-based aerogel.

[0041] In the mold method, the height of the pre-crosslinked solution in the mold is 1-10 cm, resulting in a sodium alginate-based aerogel with a thickness of 1-10 cm. The sodium alginate-based aerogel prepared in the mold method has a through-pore structure with an average pore size of 6-10 μm. By limiting the freeze-drying temperature and combining the freeze-drying temperature with the height of the solution in the mold method, a sodium alginate-based aerogel with a through-pore structure can be prepared.

[0042] The spraying method involves high-pressure spraying of a pre-crosslinked solution onto a substrate with a porosity of 30–50% and a pore size of 9–15 μm, resulting in a sodium alginate-based aerogel with a thickness of 0.5–2.5 mm. Within the aforementioned defined freeze-drying temperature range, the sodium alginate-based aerogel prepared by the spraying method exhibits a uniform spherical pore structure with an average pore size of 10–20 μm. Because the pre-crosslinked solution in the spraying method is relatively dispersed and thin, it does not affect the development of spherical pores during freeze-drying, thus ultimately resulting in a uniform spherical pore structure. In this way, by synergistically combining the freeze-drying temperature with the aerogel forming method, aerogels with different structures can be prepared, thereby controlling the drug release efficiency of drug-loaded aerogels.

[0043] Because the spraying method is suitable for preparing thin aerogels, which need to be used in combination with a substrate when applied, the substrate used is a high porosity, large pore size substrate, which is beneficial to the adsorption performance of the prepared aerogel material when used as a wound dressing.

[0044] S2. The sodium alginate-based aerogel from step S1 is placed in a calcium chloride solution with a mass fraction of 5% to 10% and reacted for 12 to 24 hours to obtain a drug-loadable aerogel.

[0045] S3. Immerse the drug-loadable aerogel from step S2 in a drug aqueous solution, allow it to adsorb for a certain period of time, and then freeze-dry it to obtain a drug-loaded aerogel wound dressing with a controllable drug release process.

[0046] This invention employs a pre-crosslinking-freeze-drying-re-crosslinking process. First, polymer nanofibers and sodium alginate are crosslinked, and then polyethyleneimine is added to form a crosslinked network structure of polymer nanofibers, sodium alginate, and polyethyleneimine. The sodium alginate-based aerogel obtained by freeze-drying is then immersed in a calcium chloride solution for crosslinking, which can form calcium ion crosslinks on the surface of the formed aerogel to obtain calcium alginate. This improves the degree of crosslinking of the aerogel, produces an aerogel with a composite structure, and further enhances the structural stability and mechanical strength of the aerogel, making it better able to meet the actual needs of wound dressings.

[0047] Specifically, in the preparation of sodium alginate-based aerogels using the mold method, sodium alginate-based aerogels of different thicknesses are obtained by limiting the height of the pre-crosslinked solution in the mold. The internal pores of this aerogel consist of long, regularly arranged through-channels. When loaded with medication and applied as a wound dressing, the uniform and oriented through-channels allow for controlled, long-term, and uniform drug release, which is beneficial for the care of slowly healing wounds. By controlling the thickness of the aerogel, the drug release time can be adjusted, allowing for targeted treatment of wounds at different stages of recovery. Thin-film sodium alginate-based aerogels prepared by the spraying method have a uniform pore structure and exhibit high drug release efficiency after loading, making them suitable for wounds that heal quickly.

[0048] Specifically, in step S1, the mass ratio of polymer nanofibers, sodium alginate, and polyethyleneimine in the pre-crosslinked solution is 1:(1.1-1.2):(0.2-0.4), preferably 1:1:0.3. By limiting the content of each component of polymer nanofibers, sodium alginate, and polyethyleneimine, an aerogel with a stable crosslinked network structure can be obtained without wasting raw materials and saving costs.

[0049] The polymer nanofibers are PVA-co-PE nanofibers, with polyethyleneimine having a molecular weight of 10,000–60,000, and the crosslinking agent is a polyaldehyde; the amount of crosslinking agent added is 0.25%–0.6% of the volume of the PVA-co-PE nanofiber suspension. The PVA-co-PE nanofibers act as a framework in the prepared aerogel. Polyethyleneimine can increase the degree of crosslinking between sodium alginate and between sodium alginate and PVA-co-PE nanofibers, thereby improving the mechanical properties of the aerogel. It also increases the hydrophilicity of the aerogel, enhancing its absorbency when applied as a wound dressing.

[0050] The sodium alginate-based aerogel prepared using the mold method was further coated with a pre-crosslinked solution under high pressure and then freeze-dried again for 12–36 hours to obtain a sodium alginate-based aerogel with an irregular internal pore structure. This irregularly structured sodium alginate-based aerogel comprises a double-layered pore structure: a bottom layer of vertically arranged pores and an upper layer of circular pores composite within the pores. When used as a drug-loaded aerogel dressing, the circular pores on the surface allow for a rapid and substantial release of medication for emergency wound treatment, while the vertically arranged pores in the bottom layer control the slow and long-term release of the medication, which is beneficial for the subsequent wound healing process.

[0051] Specifically, in step S1, the preparation of the pre-crosslinked solution includes the following steps:

[0052] S1. Prepare a polymer nanofiber suspension and add a crosslinking agent solution to obtain reaction solution I; the concentration of the polymer nanofiber suspension is 0.01-0.05 g / mL; the concentration of the crosslinking agent solution is 2.5%-7%, preferably 5%;

[0053] The preparation method of the polymer nanofiber suspension is as follows: polymer nanofibers are dispersed in a mixed solution of water and isopropanol, and centrifuged at 8000-10000 rpm for 10 min to obtain polymer nanofiber powder; the polymer nanofiber powder is placed in deionized water to obtain polymer nanofiber suspension; the volume ratio of water to isopropanol in the mixed solution is (0.5-2):1.

[0054] S2. Add sodium alginate solution to reaction solution I in step S1 under stirring, and continue stirring for 2-4 hours to obtain reaction solution II; the concentration of sodium alginate solution is 0.01-0.05 g / mL;

[0055] S3. Add the polyethyleneimine aqueous solution to the reaction solution II of step S2, and stir for 1.5 to 3 hours to obtain a pre-crosslinked solution; the mass fraction of polyethyleneimine in the polyethyleneimine aqueous solution is 1% to 10%, preferably 4% to 7%.

[0056] Example 1

[0057] This embodiment provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release, including the following steps:

[0058] S1. Disperse 3g of PVA-co-PE nanofibers in 100mL of water:isopropanol = 1 / 2 solution, centrifuge at 8000 rpm for 10 minutes to obtain nanofiber powder, disperse 2.5g of nanofibers in 50mL of deionized water and add 5mL of 5% glutaraldehyde solution to obtain reaction solution I.

[0059] S2. Add 2.5g of sodium alginate to 50mL of deionized water, stir until completely dissolved, and let stand to remove air bubbles to obtain sodium alginate solution; add 50mL of sodium alginate solution to 55mL of reaction solution I under vigorous stirring, and continue stirring for 2h to obtain reaction solution II;

[0060] S3. Weigh 0.75g of polyethyleneimine with a molecular weight of 10000 and add it to 10mL of deionized water to completely dissolve it to obtain a polyethyleneimine aqueous solution; add 10mL of polyethyleneimine aqueous solution to reaction solution II in step S2, and stir for 2h to obtain a pre-crosslinked solution.

[0061] S4. The pre-crosslinking solution containing polymer nanofiber suspension, sodium alginate solution, polyethyleneimine aqueous solution and crosslinking agent is pre-formed by mold method and frozen at -50℃ for 12h. After being taken out, it is freeze-dried for 36h to obtain sodium alginate-based aerogel with a thickness of 2cm.

[0062] S5. Weigh 15g of sodium alginate-based aerogel and add it to 150mL of 7.5% calcium chloride solution. Place it in a shaker at 150rpm and crosslink for 12h. After crosslinking, remove it and place it in 2L of deionized water for 5h to remove excess calcium ions, thus obtaining drug-loadable aerogel.

[0063] S6. Immerse 0.05g of drug-loadable aerogel in 30mL of 0.2g / L lysozyme solution for adsorption for 3h, then transfer to a freeze dryer for 24h; thus obtaining a drug-loaded aerogel wound dressing with lysozyme loading and a controllable lysozyme release process.

[0064] Please see Figures 1-2 As shown, Figure 1 This is a cross-sectional electron microscope image of the drug-loaded aerogel wound dressing containing lysozyme prepared in Example 1. Figure 2 The image shows a surface electron microscope (SEM) image of the lysozyme-loaded drug-eluting wound dressing prepared in Example 1. As can be seen from the image, the aerogel prepared by the molding method has a through-pore structure with relatively regular pore arrangement and numerous interconnected layers within the pores, which improves the mechanical strength of the aerogel.

[0065] Please see Figure 3 The figure shows the lysozyme release process of the drug-loaded aerogel wound dressing prepared in Example 1. As can be seen from the figure, this drug-loaded aerogel wound dressing slowly releases lysozyme, achieving 100% complete release after 14 days, which can provide a good therapeutic effect for chronic wounds requiring a long recovery period.

[0066] Please see Figure 4 The image shown is an infrared spectrum of the drug-loaded aerogel wound dressing containing lysozyme prepared in Example 1. As can be seen from the image, the EVOH nanofibers mainly exhibit two characteristic peaks: OH and CH. Due to the stretching of the OH peaks, the peaks are concentrated in the 3200-3400 cm⁻¹ region. -1 There is a distinct peak at 2800-3000cm. -1 and 1300-1500cm -1 The peak at 1430 cm⁻¹ corresponds to the stretching and bending of the sp₃ CH bond (-CH₂-). -1 With 1600cm -1 The characteristic peak at 3300–3500 cm⁻¹ represents the asymmetric and symmetric stretching vibrations of the carboxylic acid group (-COOH) in sodium alginate; with the addition of polyethyleneimine, the peak at 3300–3500 cm⁻¹... -1 Stretching vibrations of the NH bond occur; at 1700 cm⁻¹ -1 The obvious carbonyl vibration absorption peak shown at the point may originate from the added glutaraldehyde aldehyde group and the carboxyl group of sodium alginate.

[0067] Example 2

[0068] This embodiment provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release process. The difference from Embodiment 1 is that in step S4, the pre-crosslinked solution is sprayed onto the surface of the PP substrate using a high-pressure gun to obtain a sodium alginate-based aerogel with a thickness of 1 mm. The porosity of the substrate is 40%, and the average pore size is 12 μm. The rest is roughly the same as in Embodiment 1, and will not be repeated here.

[0069] Please see Figures 5-6 As shown, Figure 5 This is a cross-sectional electron microscope image of the drug-loaded aerogel wound dressing containing lysozyme prepared in Example 2. Figure 6 The image shows a surface electron microscope (SEM) image of the lysozyme-loaded aerogel wound dressing prepared in Example 2. The surface and cross-sectional images reveal that the aerogel prepared using the spraying method has a uniform porous structure.

[0070] Please see Figure 7The figure shows the lysozyme release process of the drug-loaded aerogel wound dressing prepared in Example 2. As can be seen from the figure, this aerogel wound dressing exhibits rapid lysozyme release, reaching 100% release within 2 days. It can be used for wounds requiring acute treatment, demonstrating good lysozyme release effect in a short time.

[0071] Example 3

[0072] This embodiment provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release process. Compared with Example 1, the difference is that in step S4, the surface of the sodium alginate-based aerogel prepared by the mold method is further coated with a pre-crosslinking solution under high pressure and then freeze-dried again for 12-36 hours to obtain a sodium alginate-based aerogel with a thickness of 2.2 cm. The rest is roughly the same as in Example 1 and will not be described again here.

[0073] Please see Figure 8 As shown, the lysozyme release process of the drug-loaded aerogel wound dressing containing lysozyme consists of two steps: the first step is ion exchange, and the second step is mass diffusion. Figure (a) shows the ion exchange process of lysozyme during release by the aerogel, which is a chemical reaction process. Figure (b) shows the diffusion process of lysozyme during release, where the mass transfers from a high concentration to a low concentration, which is a physical diffusion process. The specific test steps for lysozyme release in the drug-loaded aerogel containing lysozyme are as follows: the aerogel after adsorbing lysozyme is rinsed three times with deionized water, and then the aerogel is removed to remove excess water; the aforementioned aerogel and 0.9% NaCl solution are added to a beaker and the release test is conducted in a shaker (37℃, 150rpm). 3mL of solution is taken from each test, and the lysozyme concentration in the solution is measured using a UV spectrophotometer. The measurement is performed three times, and the average value is calculated.

[0074] The lysozyme loading capacity of the drug-loaded aerogels prepared in Examples 1-3 was tested, and the absorbance, lysozyme release efficiency, and tensile strength of the drug-loaded aerogel wound dressings were also tested. The results are shown in the table below, where the test results for lysozyme loading capacity and absorbance are expressed per gram of aerogel.

[0075] Table 1. Performance test results of aerogel wound dressings in Examples 1-3

[0076] Lysozyme loading / mg Volume of liquid absorbed / mL Lysozyme release efficiency / % Tensile strength / MPa Example 1 13.5 15 95 3.2 Example 2 1.6 2 96 22 Example 3 14.7 17 97 3.3

[0077] As shown in Table 1, the drug-loadable aerogel prepared by the molding method in Example 1 has a lysozyme loading capacity 8-10 times that of the sprayed film aerogel in Example 2, and a liquid absorption capacity 7-9 times that of the film aerogel in Example 2. The aerogel wound dressing in Example 1 had the lowest lysozyme release efficiency, but after treatment in Example 3, an aerogel wound dressing with an irregular structure was formed, which improved the lysozyme loading capacity, liquid absorption capacity, release efficiency, and tensile strength. The film aerogel in Example 2, due to its adhesion to the PP substrate, has a tensile strength of 22 MPa.

[0078] Examples 4-5

[0079] Examples 4 and 5 provide a method for preparing drug-loaded aerogel wound dressings with controllable drug release process. Compared with Example 1, the difference is that in step S4, sodium alginate-based aerogels with thicknesses of 1 cm and 8 cm are obtained by controlling the amount of pre-crosslinked solution in the mold, respectively; the rest is roughly the same as in Example 1, and will not be repeated here.

[0080] The lysozyme release time of the drug-loaded aerogel wound dressings prepared in Examples 4-5 was tested. It was found that as the thickness of the aerogel increased, the load of the aerogel on the lysozyme increased, and the release rate of the lysozyme changed from fast at first to slow and then approached a uniform release rate. Therefore, the release rate of the lysozyme can be controlled by adjusting the thickness of the aerogel.

[0081] Comparative Examples 1-2

[0082] Comparative Examples 1 and 2 provide a method for preparing a drug-loaded aerogel wound dressing with controllable drug release process. The difference from Example 1 is that in step S4, the freeze-drying temperatures are -10°C and -100°C, respectively. The rest is roughly the same as Example 1 and will not be repeated here.

[0083] When the drug-loaded aerogel wound dressings containing lysozyme prepared in Comparative Examples 1 and 2 were observed under an electron microscope, their aerogels all had round pore structures and failed to form a through-hole structure; this indicates that the freeze-drying temperature during the preparation of aerogels will affect the structure of the aerogels.

[0084] Examples 6-7

[0085] Examples 6 and 7 provide a method for preparing a drug-loaded aerogel wound dressing with controllable drug release. The difference from Example 1 is that in step S5, the mass fraction of calcium chloride solution is 5% and 10%, respectively. The rest is roughly the same as in Example 1 and will not be repeated here.

[0086] Comparative Example 3

[0087] Comparative Example 3 provides a method for preparing a drug-loaded aerogel wound dressing with a controllable drug release process. Compared with Example 1, the difference is that step S5 is not performed. The rest is roughly the same as Example 1, and will not be described again here.

[0088] Comparative Example 4

[0089] Comparative Example 4 provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release process. The difference from Example 1 is that in step S5, the mass fraction of calcium chloride solution is 15%, and the rest is roughly the same as in Example 1, which will not be repeated here.

[0090] Examples 8-9

[0091] Examples 8 and 9 provide a method for preparing a drug-loaded aerogel wound dressing with controllable drug release process. The difference from Example 1 is that in step S3, the amount of polyethyleneimine added is 0.25g and 1g, respectively. The rest is roughly the same as in Example 1 and will not be repeated here.

[0092] Comparative Example 5

[0093] Comparative Example 5 provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release process. The difference from Example 1 is that polyethyleneimine is not added to the pre-crosslinked solution. The rest is roughly the same as Example 1 and will not be repeated here.

[0094] Comparative Example 6

[0095] Comparative Example 6 provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release process. The difference from Example 1 is that in step S3, the amount of polyethyleneimine added is 2g, and the rest is roughly the same as in Example 1, which will not be repeated here.

[0096] The drug-loadable aerogels prepared in Examples 6-9 and Comparative Examples 3-6 were tested for lysozyme loading, and the performance of the drug-loaded aerogel wound dressings was tested, including liquid absorption, lysozyme release efficiency, and tensile strength. The results are shown in the table below, where the test results for lysozyme loading and liquid absorption are expressed per gram of aerogel.

[0097] Table 2. Performance test results of aerogel wound dressings in Examples 6-9 and Comparative Examples 3-6

[0098]

[0099]

[0100] Table 2 shows that, based on the data from Comparative Examples 3-4 and Examples 6-7, immersing the freeze-dried sodium alginate-based aerogel in calcium chloride for cross-linking significantly improves the tensile strength of the aerogel, further enhancing its structural stability and making it better suited for wound dressings. However, as the mass fraction of the calcium chloride solution continues to increase, the tensile strength of the aerogel does not significantly improve. Furthermore, excessive calcium chloride occupies lysozyme adsorption sites, leading to a gradual decrease in the aerogel's lysozyme loading capacity and absorbance. The lysozyme release efficiency also decreases due to the increased cross-linking degree of the aerogel. Examples 8-9 and Comparative Examples 5-6 show that increasing the amount of polyethyleneimine added effectively improves the tensile strength of the aerogel because polyethyleneimine can pre-crosslink the fiber and sodium alginate, making the aerogel structure more stable. However, polyethyleneimine has a large number of positively charged amino groups, and its addition reduces the aerogel's lysozyme loading capacity; therefore, the amount of polyethyleneimine added needs to be strictly controlled.

[0101] In summary, this invention provides a method for preparing a drug-loaded aerogel wound dressing with controllable drug release. First, a pre-crosslinked solution containing a polymer nanofiber suspension, sodium alginate solution, polyethyleneimine aqueous solution, and a crosslinking agent is pre-formed using a molding or spraying method and then completely frozen at -20℃ to -80℃. Following this, freeze-drying is performed to obtain a sodium alginate-based aerogel. Next, the sodium alginate-based aerogel is placed in a calcium chloride solution for further crosslinking to obtain a drug-loaded aerogel. Finally, the drug-loaded aerogel is immersed in a drug aqueous solution, adsorbed for a certain period, and then freeze-dried to obtain the drug-loaded aerogel wound dressing with controllable drug release. This invention modifies the structure of the aerogel by adjusting the aerogel molding method and freeze-drying parameters, thereby achieving control over the drug release process. This fills a technological gap in this area and is of great significance to the development of drug-loaded aerogel wound dressings. Through a pre-crosslinking-freeze-drying-re-crosslinking process, a drug-loaded aerogel with large drug loading capacity, dimensional stability, good mechanical properties, and controllable drug release is obtained. When applied to wound dressings, this aerogel can continuously control the drug release process, prevent bacterial infection of the wound, accelerate wound healing, and has excellent performance and broad market prospects.

[0102] The above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.

Claims

1. A method for preparing a drug-loaded aerogel wound dressing with controllable drug release process, characterized in that, Includes the following steps: S1. A pre-crosslinking solution containing polymer nanofiber suspension, sodium alginate solution, polyethyleneimine aqueous solution and crosslinking agent is pre-formed by molding or spraying, and then frozen at -20℃ to -80℃. After removal, it is freeze-dried for 12 to 48 hours to obtain sodium alginate-based aerogel; the polymer nanofiber is PVA-co-PE nanofiber. The thickness of the sodium alginate-based aerogel obtained by the mold method is 1~10cm; the spraying method is to spray the pre-crosslinked solution onto the PP substrate under high pressure, wherein the PP substrate has a porosity of 30%~50% and a pore size of 9~15µm, to obtain the sodium alginate-based aerogel with a thickness of 0.5~2.5mm. S2. The sodium alginate-based aerogel obtained in step S1 is placed in a calcium chloride solution with a mass fraction of 5%~10% and reacted for 12~24 hours to obtain a drug-loadable aerogel. S3. Immerse the drug-loadable aerogel described in step S2 in a drug aqueous solution, adsorb for 3 hours, and then freeze-dry to obtain a drug-loaded aerogel wound dressing with a controllable drug release process.

2. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 1, characterized in that, In step S1, the mass ratio of the polymer nanofibers, sodium alginate, and polyethyleneimine in the pre-crosslinked solution is 1:(1.1~1.2):(0.2~0.4).

3. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 1, characterized in that, The sodium alginate-based aerogel prepared by the mold method has a through-pore structure with an average pore size of 6~10µm; the sodium alginate-based aerogel prepared by the spraying method has a uniform circular pore structure with an average pore size of 10~20µm.

4. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 1, characterized in that, In step S1, the surface of the sodium alginate-based aerogel prepared by the mold method is further coated with the pre-crosslinked solution under high pressure, and then freeze-dried again for 12-36 hours to obtain a sodium alginate-based aerogel with an irregular internal pore structure; the irregular sodium alginate-based aerogel includes a double-layer pore structure, the bottom layer of which is a vertically arranged pore structure layer, and the upper layer is a circular pore structure layer composite with the pore structure layer.

5. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 1, characterized in that, In step S1, the preparation of the pre-crosslinked solution includes the following steps: S1. Prepare a polymer nanofiber suspension and add a crosslinking agent solution to obtain reaction solution I; the concentration of the polymer nanofiber suspension is 0.01~0.05 g / mL; S2. Add sodium alginate solution to reaction solution I obtained in step S1 under stirring, and continue stirring for 2-4 hours to obtain reaction solution II; S3. Add the polyethyleneimine aqueous solution to the reaction solution II described in step S2, and stir for 1.5 to 3 hours to obtain the pre-crosslinked solution.

6. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 5, characterized in that, In step S2, the concentration of the sodium alginate solution is 0.01~0.05 g / mL; in step S3, the mass fraction of polyethyleneimine in the polyethyleneimine aqueous solution is 1%~10%.

7. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 6, characterized in that, The polyethyleneimine aqueous solution contains 4% to 7% polyethyleneimine by mass.

8. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 5, characterized in that, In step S1, the mass fraction of the crosslinking agent solution is 2.5% to 7%.

9. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 5, characterized in that, The crosslinking agent solution has a mass fraction of 5%.

10. The method for preparing a drug-loaded aerogel wound dressing with controllable drug release process according to claim 5, characterized in that, In step S1, the polymer nanofiber suspension is prepared by dispersing polymer nanofibers in a mixed solution of water and isopropanol, centrifuging at 8000~10000 rpm for 10 min to obtain polymer nanofiber powder; placing the polymer nanofiber powder in deionized water to obtain the polymer nanofiber suspension; the volume ratio of water to isopropanol in the mixed solution is (0.5~2):1.

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