Preparation method of drug-loaded interpenetrating network hydrogel and use thereof
By preparing porous carbon nanofiber grafted chitosan/polyacrylic acid interpenetrating network hydrogels, the problem of poor biocompatibility of carbon nanofibers was solved, and efficient adsorption and sustained release of drugs were achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- 武夷学院
- Filing Date
- 2023-11-29
- Publication Date
- 2026-06-19
AI Technical Summary
When carbon nanofibers are used as drug delivery carriers, their strong hydrophilicity leads to poor biocompatibility, and existing technologies make it difficult to improve their dispersibility and stability in organisms.
Cellulose acetate/SiO2 composite nanofibers were prepared by electrospinning, followed by hydrolysis, pre-oxidation, and carbothermal reaction to prepare porous carbon nanofibers. Chitosan and polyacrylic acid were then grafted onto their surfaces to form a porous carbon nanofiber-grafted chitosan/polyacrylic acid interpenetrating network hydrogel, which was then used for drug loading via electrostatic adsorption.
The improved hydrophilicity and biocompatibility of porous carbon nanofibers enable efficient adsorption and sustained release of drugs, making them suitable as drug sustained-release materials.
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Figure CN117643843B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to a method for preparing a drug-loaded interpenetrating network hydrogel, belonging to the field of functional polymer materials. Background Technology
[0002] Hydrogels are a class of highly hydrophilic three-dimensional network gels that swell rapidly in water and retain a large volume of water without dissolving. They also possess excellent biocompatibility, superior physical and mechanical properties, and long-term implantation stability. Integral polymers (IPNs) are unique polymer blends or alloys formed by the interpenetrating entanglement of two or more polymers. The unique cellular structure, interpenetrating interfaces, and biphase continuity of IPNs result in special synergistic effects in their performance and function, preventing phase separation and significantly improving the mechanical strength of the hydrogel. Carbon nanofibers are fibrous nanomaterials made by rolling up graphite sheets; they are quasi-one-dimensional carbon materials, intermediate between ordinary carbon fibers and carbon nanotubes. Due to their high specific modulus, high specific strength, high electrical conductivity, large aspect ratio, and large specific surface area, carbon nanofibers have been widely used in medical, aerospace, transportation, and mechanical fields. However, carbon nanofibers, as carriers for drug release, tend to aggregate in organisms due to their strong hydrophilicity, resulting in poor biocompatibility. Therefore, improving the hydrophilicity of carbon nanofibers is the only way to enhance their biocompatibility. Summary of the Invention:
[0003] To address the aforementioned technical problems, the purpose of this invention is to provide a method for preparing a drug-loaded interpenetrating network hydrogel and its applications.
[0004] This invention is achieved through the following technical solution:
[0005] A method for preparing a drug-loaded interpenetrating network hydrogel includes the following steps:
[0006] S1. Cellulose acetate / SiO2 composite nanofibers were prepared by electrospinning.
[0007] S2. The cellulose acetate / SiO2 composite nanofibers are hydrolyzed by soaking them in a NaOH / ethanol solution to obtain cellulose / SiO2 composite nanofibers.
[0008] S3. The cellulose / SiO2 composite nanofibers are subjected to pre-oxidation and carbothermal reaction in sequence to obtain porous carbon nanofibers.
[0009] S4. After activating the porous carbon nanofibers with concentrated nitric acid, add them together with the phosphate ester. N,NAfter being evenly dispersed in dimethylformamide, chitosan acetate solution was added, mixed well, and reacted at 65~75℃ to obtain porous carbon nanofibers grafted with chitosan.
[0010] S5. Graft the porous carbon nanofibers with chitosan and acrylic acid. N,N - Methylenebisacrylamide and ammonium persulfate were added to distilled water and dispersed evenly. Then, under the protection of nitrogen, a polymerization reaction was initiated by ultraviolet light to obtain the porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material.
[0011] S6. The porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material is added to an ibuprofen / ethanol solution. After the porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material reaches adsorption equilibrium with ibuprofen molecules, it is filtered, the filter cake is collected, unadsorbed ibuprofen molecules are washed away, and it is vacuum dried to obtain the drug-loaded interpenetrating network hydrogel.
[0012] As a preferred embodiment, the method for preparing the cellulose acetate / SiO2 composite nanofibers is as follows:
[0013] Add cellulose acetate and tetraethyl orthosilicate N,N Dissolve the dimethylacetamide and acetone in a mixed solvent to obtain a spinning solution;
[0014] After the spinning solution is spun using an electrospinning device, it is dried under vacuum to obtain cellulose acetate / SiO2 composite nanofibers.
[0015] As a preferred embodiment, the spinning solution contains cellulose acetate at a mass concentration of 5-15% and tetraethyl orthosilicate at a mass concentration of 1-5%. N,N The mass ratio of dimethylacetamide to acetone is (2~4):(1~2).
[0016] As a preferred embodiment, the electrospinning conditions are: spinning voltage 20~30 kV, distance between spinning needle and collecting plate 10~20 cm, and spinning speed 0.2~0.3 mL / h.
[0017] As a preferred embodiment, the concentration of the NaOH / ethanol solution is 0.1~0.3 mol / L.
[0018] As a preferred embodiment, the pre-oxidation conditions are: under nitrogen protection, the temperature is maintained at 250~300 ℃ for 2 hours.
[0019] As a preferred embodiment, the carbothermic reaction conditions are as follows: under nitrogen protection, the temperature is raised from 250~300 ℃ to 900~1000 ℃ and reacted for 3 hours, then reacted for 3 hours in a chlorine atmosphere, and finally cooled naturally to room temperature under nitrogen protection.
[0020] As a preferred embodiment, the mass ratio of the activated porous carbon nanofibers to phosphate esters is (3~5):(1~2); the mass ratio of the porous carbon nanofibers grafted with chitosan to acrylic acid is (2~5):(1~2).
[0021] As a preferred embodiment, the mass concentration of the ibuprofen / ethanol solution is 0.1~0.3%.
[0022] As a preferred embodiment, the phosphate ester is trimethyl phosphate.
[0023] The use of a drug-loaded interpenetrating network hydrogel prepared by the aforementioned method in drug sustained-release materials.
[0024] The basic principle of this invention is as follows:
[0025] 1. Cellulose acetate and tetraethyl orthosilicate were used as precursors to prepare cellulose acetate / SiO2 composite nanofibers by electrospinning. Porous carbon nanofibers were then obtained through a series of hydrolysis, pre-oxidation, carbothermal reaction and carbothermal reduction.
[0026] 2. By using nitric acid to activate the carbon nanofibers, carboxyl groups are introduced onto the surface of the porous carbon nanofibers. The amino groups on chitosan react with the carboxyl groups, allowing chitosan to be grafted onto the porous carbon nanofibers.
[0027] 3. Using porous carbon nanofibers grafted with chitosan as the backbone, acrylic acid is combined with nanofibers through an interpenetrating network structure to obtain porous carbon nanofibers grafted with chitosan / polyacrylic acid interpenetrating network hydrogel.
[0028] Compared with the prior art, the present invention has the following beneficial effects:
[0029] 1. By utilizing the high porosity and large specific surface area of porous carbon nanofibers, ibuprofen is adsorbed into the pores of the fibers through electrostatic adsorption, thereby achieving the purpose of drug loading.
[0030] 2. By utilizing the strong hydrophilicity of polyacrylic acid, the hydrophilicity of porous carbon nanofibers can be improved, thereby enhancing their dispersibility in cells and improving the biocompatibility of drug-loaded hydrogels. Attached Figure Description
[0031] Other features, objects, and advantages of the present invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:
[0032] Figure 1 This is a roadmap for the preparation of drug-loaded interpenetrating network hydrogels. Detailed Implementation
[0033] The present invention will now be described in detail with reference to specific embodiments. These embodiments will help those skilled in the art to further understand the present invention, but do not limit the invention in any way. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention. These all fall within the scope of protection of the present invention.
[0034] Example 1
[0035] 1) Porous carbon nanofibers
[0036] Add 1 g of cellulose acetate and 0.2 g of tetraethyl orthosilicate to 10 g of... N,N - Dimethylacetamide and 5 g acetone were mixed and dissolved in a magnetically stirred solution at room temperature to obtain a spinning solution. The solution was spun using an electrospinning apparatus with a spinning voltage of 30 kV, a distance of 20 cm between the spinning needle and the collecting plate, and a spinning speed of 0.3 mL / h. The spun membrane was peeled off from aluminum foil and vacuum dried to obtain cellulose acetate / SiO2 composite nanofibers. The cellulose acetate / SiO2 composite nanofibers were then immersed in a 0.25 mol / L NaOH / ethanol solution for 24 h to obtain cellulose / SiO2 composite nanofibers. Under nitrogen protection, the cellulose / SiO2 composite nanofibers were pre-oxidized at 250 ℃ for 2 h in an atmosphere furnace, followed by a carbothermic reaction at 950 ℃ for 3 h. Finally, chlorine gas was introduced while maintaining the temperature for another 3 h. After the reaction, nitrogen gas was introduced, and the mixture was allowed to cool naturally to room temperature to obtain porous carbon nanofibers.
[0037] 2) Porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel
[0038] 1 g of porous carbon nanofibers was activated with concentrated nitric acid at 60 °C for 3 h, washed repeatedly with distilled water until neutral, and dried in an empty drying oven at 60 °C for 24 h. 0.6 g of activated porous carbon nanofibers and 0.15 g of trimethyl phosphate were added to 200 g of... N,N In dimethylformamide solvent, the mixture was ultrasonically dispersed for 5 min. 0.2 g of chitosan was dissolved in 100 mL of 1% glacial acetic acid solution. The chitosan solution was then added to the above solution, and ultrasonication continued for 10 min. The mixture was reacted at 70 °C for 3 h. After the reaction, the fibers were washed and dried to obtain porous carbon nanofibers grafted with chitosan. 1 g of porous carbon nanofibers grafted with chitosan, 0.5 g of acrylic acid, and 0.01 g of... N,NMethylenebisacrylamide and 0.01 g ammonium persulfate were added to 20 mL of distilled water and magnetically stirred to form a mixture. Under nitrogen protection, the mixture was irradiated under a 365 nm UV lamp for 20 min. After washing and drying, a porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material was obtained.
[0039] 3) Preparation of drug-loaded interpenetrating network hydrogels
[0040] 0.15 g of interpenetrating network hydrogel was added to 200 mL of ibuprofen / ethanol solution with a concentration of 0.2 mol / L. The solution was magnetically stirred for 24 h at room temperature to reach adsorption equilibrium. The solution was filtered, and the filter cake was washed with ethanol to remove ibuprofen molecules adsorbed on the fiber surface. The solution was then vacuum dried at 60 °C for 24 h to obtain the drug-loaded interpenetrating network hydrogel.
[0041] Taking the drug-loaded interpenetrating network hydrogel prepared in Example 1 as an example, the release of ibuprofen in 0.9% NaCl solution was only 18.9% after immersion for 3 hours, and the release of ibuprofen reached equilibrium after 24 hours. This indicates that the interpenetrating network hydrogel prepared in this invention can be used as a carrier for sustained drug release.
[0042] Example 2
[0043] 1) Porous carbon nanofibers
[0044] Add 1.3 g of cellulose acetate and 0.25 g of tetraethyl orthosilicate to 15 g of... N,N The solution was dissolved in a mixture of dimethylacetamide and 3 g acetone at room temperature with magnetic stirring to obtain a spinning solution. The solution was spun using an electrospinning apparatus at a spinning voltage of 20 kV, a distance of 15 cm between the spinning needle and the collecting plate, and a spinning speed of 0.25 mL / h. The spun membrane was peeled off from aluminum foil and vacuum dried to obtain cellulose acetate / SiO2 composite nanofibers. The cellulose acetate / SiO2 composite nanofibers were then immersed in a 0.1 mol / L NaOH / ethanol solution for 24 h to obtain cellulose / SiO2 composite nanofibers. Under nitrogen protection, the cellulose / SiO2 composite nanofibers were pre-oxidized at 300 °C for 2 h in an atmosphere furnace, followed by a carbothermic reaction at 1000 °C for 3 h. Finally, chlorine gas was introduced while maintaining the temperature for another 3 h. After the reaction, nitrogen gas was introduced, and the mixture was allowed to cool naturally to room temperature to obtain porous carbon nanofibers.
[0045] 2) Porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel
[0046] 1.2 g of porous carbon nanofibers were activated with concentrated nitric acid at 60 °C for 3 h, washed repeatedly with distilled water until neutral, and dried in an empty drying oven at 60 °C for 24 h. 0.5 g of activated porous carbon nanofibers and 0.12 g of trimethyl phosphate were added to 200 g of... N, N In dimethylformamide solvent, the mixture was ultrasonically dispersed for 5 min. 0.2 g of chitosan was dissolved in 100 mL of 1% glacial acetic acid solution. The chitosan solution was then added to the above solution, and ultrasonication continued for 10 min. The mixture was reacted at 73 ℃ for 3 h. After the reaction, the fibers were washed and dried to obtain porous carbon nanofibers grafted with chitosan. 1.2 g of porous carbon nanofibers grafted with chitosan, 0.6 g of acrylic acid, and 0.01 g of... N,N Methylenebisacrylamide and 0.01 g ammonium persulfate were added to 20 mL of distilled water and magnetically stirred to form a mixture. Under nitrogen protection, the mixture was irradiated under a 365 nm UV lamp for 20 min. After washing and drying, a porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material was obtained.
[0047] 3) Preparation of drug-loaded interpenetrating network hydrogels
[0048] 0.15 g of interpenetrating network hydrogel was added to 200 mL of ibuprofen / ethanol solution with a concentration of 0.15 mol / L. The solution was magnetically stirred for 24 h at room temperature to reach adsorption equilibrium. The solution was filtered, and the filter cake was washed with ethanol to remove ibuprofen molecules adsorbed on the fiber surface. The solution was then vacuum dried at 60 °C for 24 h to obtain the drug-loaded interpenetrating network hydrogel.
[0049] Taking the drug-loaded interpenetrating network hydrogel prepared in Example 2 as an example of release in 0.9% NaCl solution, the ibuprofen release was only 19.01% after immersion for 3 hours, and the release of ibuprofen reached equilibrium after 24 hours. This indicates that the interpenetrating network hydrogel prepared in this invention can be used as a carrier for sustained drug release.
[0050] Example 3
[0051] 1) Porous carbon nanofibers
[0052] Add 1.5 g of cellulose acetate and 0.2 g of tetraethyl orthosilicate to 15 g of... N,NThe solution was dissolved in a mixture of dimethylacetamide and 5 g acetone at room temperature with magnetic stirring to obtain a spinning solution. The solution was spun using an electrospinning apparatus at a spinning voltage of 25 kV, a distance of 15 cm between the spinning needle and the collecting plate, and a spinning speed of 0.2 mL / h. The spun membrane was peeled off from aluminum foil and vacuum dried to obtain cellulose acetate / SiO2 composite nanofibers. The cellulose acetate / SiO2 composite nanofibers were then immersed in a 0.2 mol / L NaOH / ethanol solution for 24 h to obtain cellulose / SiO2 composite nanofibers. Under nitrogen protection, the cellulose / SiO2 composite nanofibers were pre-oxidized at 270 ℃ for 2 h in an atmosphere furnace, followed by a carbothermic reaction at 950 ℃ for 3 h. Finally, chlorine gas was introduced while maintaining the temperature for another 3 h. After the reaction, nitrogen gas was introduced, and the mixture was allowed to cool naturally to room temperature to obtain porous carbon nanofibers.
[0053] 2) Porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel
[0054] 1.2 g of porous carbon nanofibers were activated with concentrated nitric acid at 60 °C for 3 h, washed repeatedly with distilled water until neutral, and dried in an empty drying oven at 60 °C for 24 h. 0.5 g of activated porous carbon nanofibers and 0.1 g of trimethyl phosphate were added to 200 g of... N,N In dimethylformamide solvent, the mixture was ultrasonically dispersed for 5 min. 0.2 g of chitosan was dissolved in 100 mL of 1% glacial acetic acid solution. The chitosan solution was then added to the above solution, and ultrasonication continued for 10 min. The mixture was reacted at 78 ℃ for 3 h. After the reaction, the fibers were washed and dried to obtain porous carbon nanofibers grafted with chitosan. 1 g of porous carbon nanofibers grafted with chitosan, 0.6 g of acrylic acid, and 0.01 g of... N,N Methylenebisacrylamide and 0.01 g ammonium persulfate were added to 20 mL of distilled water and magnetically stirred to form a mixture. Under nitrogen protection, the mixture was irradiated under a 365 nm UV lamp for 20 min. After washing and drying, a porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material was obtained.
[0055] 3) Preparation of drug-loaded interpenetrating network hydrogels
[0056] 0.15 g of interpenetrating network hydrogel was added to 200 mL of ibuprofen / ethanol solution with a concentration of 0.15 mol / L. The solution was magnetically stirred for 24 h at room temperature to reach adsorption equilibrium. The solution was filtered, and the filter cake was washed with ethanol to remove ibuprofen molecules adsorbed on the fiber surface. The solution was then vacuum dried at 60 °C for 24 h to obtain the drug-loaded interpenetrating network hydrogel.
[0057] Taking the drug-loaded interpenetrating network hydrogel prepared in Example 3 as an example of release in 0.9% NaCl solution, the release of ibuprofen was only 17.22% after immersion for 3 hours, and the release of ibuprofen reached equilibrium after 24 hours. This indicates that the interpenetrating network hydrogel prepared in this invention can be used as a carrier for sustained drug release.
[0058] Comparative Example 1
[0059] Unlike Example 1, Comparative Example 1 directly used porous carbon nanofibers for the release of ibuprofen. After 3 hours, the release of ibuprofen from the porous carbon nanofibers prepared in Comparative Example 1 reached 60.14%, and the release equilibrium was reached after 5 hours.
[0060] Comparative Example 2
[0061] Unlike Example 1, Comparative Example 2 did not undergo chitosan grafting modification, and the final product was a porous carbon nanofiber / polyacrylic acid interpenetrating network hydrogel. After soaking for 3 hours, the ibuprofen release of the porous carbon nanofiber / polyacrylic acid interpenetrating network hydrogel prepared in Comparative Example 1 reached 34.12%, and the release reached equilibrium after 9 hours.
[0062] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.
Claims
1. A method for preparing a drug-loaded interpenetrating network hydrogel, characterized by, Includes the following steps: S1. Cellulose acetate / SiO2 composite nanofibers were prepared by electrospinning. S2. The cellulose acetate / SiO2 composite nanofibers are hydrolyzed by soaking them in a NaOH / ethanol solution to obtain cellulose / SiO2 composite nanofibers. S3. The cellulose / SiO2 composite nanofibers are subjected to pre-oxidation and carbothermal reaction in sequence to obtain porous carbon nanofibers. S4. After activating the porous carbon nanofibers with concentrated nitric acid, add them together with the phosphate ester. N,N After being evenly dispersed in dimethylformamide, chitosan acetate solution was added, mixed well, and reacted at 65~75℃ to obtain porous carbon nanofibers grafted with chitosan. S5. Graft the porous carbon nanofibers with chitosan and acrylic acid. N,N - Methylenebisacrylamide and ammonium persulfate were added to distilled water and dispersed evenly. Then, under the protection of nitrogen, a polymerization reaction was initiated by ultraviolet light to obtain the porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material. S6. The porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material is added to the ibuprofen / ethanol solution. After the porous carbon nanofiber grafted chitosan / polyacrylic acid interpenetrating network hydrogel material reaches the adsorption equilibrium of ibuprofen molecules, the mixture is filtered, the filter cake is collected, the unadsorbed ibuprofen molecules are washed away, and the mixture is vacuum dried to obtain the drug-loaded interpenetrating network hydrogel. The conditions for the carbothermic reaction are as follows: under nitrogen protection, the temperature is raised from 250~300 ℃ to 900~1000 ℃ and reacted for 3 hours, then reacted for 3 hours in a chlorine atmosphere, and finally cooled naturally to room temperature under nitrogen protection.
2. The method for preparing the drug-loaded interpenetrating network hydrogel as described in claim 1, characterized in that, The preparation method of the cellulose acetate / SiO2 composite nanofibers is as follows: Add cellulose acetate and tetraethyl orthosilicate N,N Dissolve the dimethylacetamide and acetone in a mixed solvent to obtain a spinning solution; After the spinning solution is spun using an electrospinning device, it is dried under vacuum to obtain cellulose acetate / SiO2 composite nanofibers.
3. The method for preparing the drug-loaded interpenetrating network hydrogel as described in claim 2, characterized in that, In the spinning solution, the mass concentration of cellulose acetate is 5-15%, and the mass concentration of tetraethyl orthosilicate is 1-5%. N,N The mass ratio of dimethylacetamide to acetone is (2~4):(1~2).
4. The method of claim 2, wherein the drug-loaded interpenetrating network hydrogel is prepared by the steps of: The conditions for electrospinning are: spinning voltage 20~30 kV, distance between spinning needle and collecting plate 10~20 cm, and spinning speed 0.2~0.3 mL / h.
5. The method of claim 1, wherein the drug-loaded interpenetrating network hydrogel is prepared by the steps of: The concentration of the NaOH / ethanol solution is 0.1~0.3 mol / L.
6. The method of claim 1, wherein the drug-loaded interpenetrating network hydrogel is prepared by the steps of: The pre-oxidation conditions are as follows: under nitrogen protection, the temperature is maintained at 250~300 ℃ for 2 hours.
7. The method for preparing the drug-loaded interpenetrating network hydrogel as described in claim 1, characterized in that, The activated porous carbon nanofibers and phosphate esters have a mass ratio of (3~5):(1~2); the porous carbon nanofibers grafted with chitosan and acrylic acid have a mass ratio of (2~5):(1~2).
8. The method for preparing the drug-loaded interpenetrating network hydrogel as described in claim 1, characterized in that, The mass concentration of the ibuprofen / ethanol solution is 0.1~0.3%.
9. The use of a drug-loaded interpenetrating network hydrogel obtained by the preparation method as described in claim 1 in drug sustained-release materials.
Citation Information
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