A pH-induced photothermal enhanced cellulose hydrogel and a preparation method and application thereof
By preparing pH-induced photothermal enhanced cellulose hydrogels, the problem of insufficient photothermal performance of traditional hydrogels under different pH conditions was solved, achieving efficient antibacterial and drug delivery in the treatment of subcutaneous abscesses, reducing thermal damage and possessing shape adaptability.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- GUANGXI UNIV
- Filing Date
- 2023-07-04
- Publication Date
- 2026-06-02
AI Technical Summary
Traditional photostimulation-responsive hydrogels are difficult to exhibit different photothermal properties under different pH conditions, and they are prone to causing thermal damage to surrounding healthy tissues in the treatment of subcutaneous abscesses. At the same time, the application of single-stimulus-responsive hydrogels is limited in complex scenarios.
A pH-induced photothermal enhanced cellulose hydrogel was prepared by grafting polyaniline and modified taurine onto the surface of cellulose nanocrystals through steps such as TEMPO oxidation and Schiff base reaction, and combining it with Pluronic F68 to form drug-loaded micelles, thereby endowing it with pH-induced photothermal enhancement, hydrogen peroxide-stimulated carbon monoxide release, and temperature responsiveness.
It exhibits thermal differential properties under different pH conditions, reducing thermal damage to healthy tissues, achieving highly efficient antibacterial activity and controlled drug release, and is shape-adaptable and injectable, making it suitable for the treatment of subcutaneous abscesses.
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomass fiber modification technology, specifically relating to a pH-induced photothermal enhanced cellulose hydrogel, its preparation method, and its application. Background Technology
[0002] Stimulus-responsive hydrogels can change their physical or chemical properties in response to external environmental stimuli, showing broad application prospects in drug delivery and subcutaneous abscess treatment. Among the stimuli, temperature, pH, hydrogen peroxide, and light have been widely studied in recent years. Furthermore, current research focuses primarily on single-stimulus-responsive hydrogels, but their limited single-stimulus-response function restricts their practical application in complex scenarios. Therefore, research on multi-stimulus-responsive hydrogels is of paramount importance.
[0003] Subcutaneous abscesses, a type of localized skin infection, are usually caused by pathogens in the infected area. Frequent antibiotic administration can easily lead to bacterial resistance, and surgical treatment of subcutaneous abscesses can cause severe pain for patients; therefore, the treatment of subcutaneous abscesses remains a significant challenge. Photothermal therapy, a treatment strategy that uses photothermal agents to convert light energy into heat energy to ablate bacteria under specific wavelengths of light, has attracted considerable attention from researchers in the field of subcutaneous abscess treatment due to its unique advantages such as high spatiotemporal control precision, non-contact remote operation, and sensitive light response.
[0004] Currently, much research focuses on using stimulus-responsive hydrogels to convert light energy into heat energy via photothermal agents for non-thermally differential antibacterial treatment under phototriggered conditions. However, because the abscess cavity of a subcutaneous abscess is surrounded by normal healthy tissue, non-thermally differential photothermal treatment of the abscess can easily cause thermal damage to the surrounding healthy tissue, affecting the treatment effect. Since there is a pH difference between the abscess cavity of a subcutaneous abscess (pH = 6.0–6.6) and the surrounding healthy tissue (pH = 7.4), this pH difference can be utilized to endow stimulus-responsive hydrogels with pH-induced photothermal enhancement properties, which allows for efficient antibacterial treatment in slightly acidic environments with pH-induced photothermal enhancement, while reducing thermal damage to surrounding healthy tissue. Furthermore, endowing the hydrogel with pH-responsive drug release control properties is of positive significance for promoting the application of stimulus-responsive hydrogels in drug delivery. Furthermore, leveraging the hydrogen peroxide overexpression characteristic of the inflammatory environment in subcutaneous abscesses, the hydrogel can be endowed with the ability to generate carbon monoxide upon hydrogen peroxide stimulation, which is beneficial for achieving the antibacterial therapeutic effect of carbon monoxide gas. Utilizing the temperature difference between the external environment and the human body, the hydrogel can undergo a sol-gel transition, making it injectable at room temperature. When injected into a body-temperature environment, it can gel in situ in response to body temperature, giving it shape adaptability. On the other hand, due to the good biocompatibility, ease of chemical modification, and wide availability of natural polymer cellulose nanocrystals, they are an excellent matrix for stimulus-responsive hydrogels and have received widespread attention from researchers in recent years. Therefore, research on a pH-induced photothermal enhanced cellulose hydrogel, its preparation method, and its application in drug delivery to provide a therapeutic strategy for subcutaneous abscess treatment is of great significance. Summary of the Invention
[0005] The purpose of this invention is to provide a pH-induced photothermal enhanced cellulose hydrogel, its preparation method, and its applications. This hydrogel exhibits pH-induced photothermal enhancement properties, meaning that under near-infrared light and pH stimulation, it responds to pH values, achieving a pH-induced photothermal enhancement effect with thermal differences under different pH environments. This solves the problem that traditional photostimulation-responsive hydrogels cannot exhibit different photothermal properties under different pH environments. Simultaneously, it can generate carbon monoxide under hydrogen peroxide stimulation, controllably release anti-inflammatory drugs under pH stimulation, and undergo a sol-gel transition at temperatures above 33°C, giving it good injectability and shape adaptability.
[0006] The above-mentioned objectives of the present invention are achieved through the following technical solutions:
[0007] A method for preparing a pH-induced photothermal enhanced cellulose hydrogel includes the following preparation steps:
[0008] S1. Preparation of carboxylated cellulose nanocrystals: The hydroxyl groups on C6 of the cellulose nanocrystal structural units were oxidized to carboxyl groups by TEMPO oxidation. The degree of oxidation was controlled by adjusting the reaction conditions to prepare carboxylated cellulose nanocrystals.
[0009] S2. Preparation of dialdehyde cellulose nanocrystals: Dialdehyde cellulose nanocrystals were prepared by selectively oxidizing the hydroxyl groups on C2 and C3 of the cellulose nanocrystal structural units to aldehyde groups using sodium periodate.
[0010] S3. Preparation of pH / NIR responsive cellulose nanocrystals: pH / NIR responsive cellulose nanocrystals were prepared by chemically grafting intrinsic polyaniline onto the surface of carboxylated cellulose nanocrystals using an amidation reaction; the pH / NIR responsive properties of the pH / NIR responsive cellulose nanocrystals were imparted by the photothermal agent intrinsic polyaniline.
[0011] S4. Preparation of pH-responsive drug-loaded cellulose nanocrystals: pH-responsive drug-loaded cellulose nanocrystals were prepared by chemically modifying the surface of dialdehyde cellulose nanocrystals with taurine using the Schiff base reaction; the taurine is a sulfur-containing amino acid drug with anti-inflammatory effects.
[0012] S5. Preparation of drug-loaded micelles: Pranic F68 was fully dissolved in deionized water, and then manganese pentacarbonyl bromide was added to it. The mixture was then stirred thoroughly at room temperature to prepare drug-loaded micelles. The Pranic F68 is a poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) triblock copolymer, which is a temperature-sensitive reagent with temperature response characteristics. The manganese pentacarbonyl bromide is a carbon monoxide donor and can generate carbon monoxide under the stimulation of hydrogen peroxide.
[0013] S6. Add the pH / near-infrared light-responsive cellulose nanocrystals obtained in step S3 to deionized water and disperse them evenly. Then add the pH-responsive drug-loaded cellulose nanocrystals obtained in step S4 and stir evenly. Finally, add the drug-loaded micelles obtained in step S5 to the mixture and stir thoroughly. Heat to evaporate the water to control the solid content of the product to 14.4-17.2% to obtain pH-induced photothermal enhanced cellulose hydrogel.
[0014] Further, the main operation of step S1 is as follows: First, cellulose nanocrystals are added to deionized water and dispersed evenly. Then, TEMPO, NaBr, and sodium hypochlorite solution are added in sequence. Then, magnetic stirring is performed at room temperature. The pH of the entire system is adjusted to 10 using sodium hydroxide. Magnetic stirring is performed at 55-65℃. After oxidation for 15-19 hours, anhydrous ethanol is added to terminate the reaction. After washing and drying, the final product is carboxylated cellulose nanocrystals. The mass ratio of cellulose nanocrystals to TEMPO is 50:1 to 70:1. The mass ratio of cellulose nanocrystals to NaBr is 3:1.
[0015] Further, the main operation of step S2 is as follows: First, cellulose nanocrystals are added to potassium hydrogen phthalate buffer solution and stirred evenly. Then, sodium periodate is added to the solution and reacted in the dark at 35-39°C for 3-5 hours. Finally, ethylene glycol is added to the reaction mixture to end the reaction. After washing and drying, the final product is dialdehyde cellulose nanocrystals. The mass ratio of cellulose nanocrystals to sodium periodate is 2:1 to 2:1.4.
[0016] Further, the main operation of step S3 is as follows: First, the carboxylated cellulose nanocrystals obtained in step S1 are added to deionized water and dispersed evenly. Then, N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added to activate the carboxyl groups for 1 hour. Subsequently, intrinsic polyaniline is dissolved in N-methylpyrrolidone and added dropwise to the activated reaction mixture, and the mixture is magnetically stirred at room temperature for 24-72 hours. After the reaction is completed, N... The mixture was centrifuged and washed using methylpyrrolidone as the washing liquid. Subsequently, deionized water was used as the dialysis medium to dialyze the centrifuged product. After drying, the final product obtained was pH / near-infrared responsive cellulose nanocrystals. The mass ratio of the carboxylated cellulose nanocrystals, N-hydroxysuccinimide, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride was 1:1:1, and the mass ratio of the carboxylated cellulose nanocrystals to intrinsic polyaniline was 5:1.
[0017] Further, the main operation of step S4 is as follows: First, the dialdehyde cellulose nanocrystals obtained in step S2 are added to deionized water and dispersed evenly. Then, taurine is added to the solution, and the mixture is magnetically stirred and reacted at 55-65°C in the dark for 36-72 hours. Finally, the product is dialyzed and freeze-dried to obtain the final product, which is pH-responsive drug-loaded cellulose nanocrystals. The mass ratio of the dialdehyde cellulose nanocrystals to taurine is 1:3.
[0018] Furthermore, the mass ratio of Prönnick F68 to manganese pentacarbonyl bromide is 100:1 to 125:1.
[0019] Furthermore, the mass ratio of the pH / near-infrared light-responsive cellulose nanocrystals to the pH-responsive drug-loaded cellulose nanocrystals is 1:4.7 to 1:6.0, and the mass ratio of the pH / near-infrared light-responsive cellulose nanocrystals to the drug-loaded micelles is 1:4.4 to 1:7.3.
[0020] Furthermore, the heating and evaporation temperature in step S6 is 40°C.
[0021] The pH-induced photothermal enhanced cellulose hydrogel of the present invention has pH-induced photothermal enhancement properties, and can generate carbon monoxide under hydrogen peroxide stimulation, release anti-inflammatory drugs in a controlled manner under pH stimulation, and can undergo sol-gel transition in response to temperatures above 33°C.
[0022] The pH-induced photothermal enhanced cellulose hydrogel of this invention can be applied in the field of drug delivery and provides a treatment strategy for subcutaneous abscesses. When used for subcutaneous abscess treatment, due to the difference in pH between the slightly acidic environment of the abscess cavity (pH = 6.0–6.6) and the surrounding healthy tissue (pH = 7.4), the pH-induced photothermal enhanced cellulose hydrogel, under near-infrared light and pH stimulation, can impart photothermal properties with thermal differences under different pH environments. This is beneficial for its efficient antibacterial effect in slightly acidic environments with pH-induced photothermal enhancement, while reducing thermal damage to surrounding healthy tissues. Furthermore, the pH-induced photothermal enhanced cellulose hydrogel can generate carbon monoxide under hydrogen peroxide stimulation, achieving an antibacterial effect; and can controllably release the anti-inflammatory drug taurine under pH stimulation. Simultaneously, the pH-induced photothermal enhanced cellulose hydrogel can respond to sol-gel transitions above 33°C, giving it good injectability and shape adaptability.
[0023] The present invention has the following beneficial effects:
[0024] (1) The pH-induced photothermal enhanced cellulose hydrogel prepared by this invention exhibits pH-induced photothermal enhancement properties. Specifically, after 200 s of near-infrared light irradiation, the temperature of the hydrogel at pH = 6.3 is significantly higher than that at pH = 7.4 (temperature difference greater than 3.8℃). This pH-induced photothermal enhancement property endows the hydrogel with photothermal properties exhibiting thermal differences under different pH conditions. This solves the problem that traditional photostimulation-responsive hydrogels struggle to exhibit different photothermal properties under different pH conditions.
[0025] (2) This invention utilizes dialdehyde cellulose nanocrystals as a matrix and chemically modifies the surface of the anti-inflammatory drug taurine onto the dialdehyde cellulose nanocrystals via a Schiff base reaction to obtain pH-responsive drug-loaded cellulose nanocrystals with imine bonds, which are then incorporated into a hydrogel. By cleverly utilizing the property that imine bonds break in response to acidic pH values, the hydrogel is endowed with pH-responsive, controllable drug release properties. Specifically, after 27 hours of drug release, the cumulative drug release at pH = 6.3 is significantly higher than that at pH = 6.8. Therefore, the pH-responsive, controllable drug release properties of the pH-induced photothermal enhanced cellulose hydrogel can provide support for its application in the field of drug delivery.
[0026] (3) This invention utilizes Pluronic F68, which has temperature-responsive properties, to load carbon monoxide donor manganese pentacarbonyl bromide to form drug-loaded micelles, and introduces them into hydrogels, endowing the hydrogel with temperature-responsive properties and the ability to generate carbon monoxide under hydrogen peroxide stimulation. Pluronic F68 is a triblock copolymer with hydrophilic end blocks and hydrophobic middle blocks. Through hydrophobic interactions, manganese pentacarbonyl bromide can be loaded by Pluronic F68 to form drug-loaded micelles, solving the problem that the hydrophobic nature of manganese pentacarbonyl bromide, a carbon monoxide donor, makes it difficult to apply. Furthermore, the pH-induced photothermal enhanced cellulose hydrogel can respond to sol-gel transitions above 33°C, making it injectable at room temperature. When injected into a simulated human body temperature environment (37°C), it can respond to temperature and undergo in-situ gelation, giving it shape adaptability. Detailed Implementation
[0027] Example 1
[0028] S1. Preparation of carboxylated cellulose nanocrystals: 2.0 g of cellulose nanocrystals were added to an Erlenmeyer flask containing 200.0 mL of deionized water and dispersed evenly. Then, 40.0 mg of TEMPO and 666.7 mg of NaBr were added. Finally, 1.84 M and 1.2 mL of sodium hypochlorite solution were added, and the mixture was magnetically stirred at room temperature. The pH of the entire system was adjusted to 10 using sodium hydroxide, and the mixture was magnetically stirred at 600 rpm and 55 °C. After oxidation for 15 h, 6.0 mL of anhydrous ethanol was added to terminate the reaction. After washing and drying, carboxylated cellulose nanocrystals were obtained.
[0029] S2. Preparation of dialdehyde cellulose nanocrystals: 4.0 g of cellulose nanocrystals were added to an Erlenmeyer flask containing 100.0 mL of potassium hydrogen phthalate buffer solution (0.05 M, pH = 3) and stirred until homogeneous. Then, 2.0 g of sodium periodate was added, and the mixture was stirred and reacted in the dark at 35 °C for 3 h. Finally, 10.0 mL of ethylene glycol was added to the reaction mixture to terminate the reaction. After washing and drying, dialdehyde cellulose nanocrystals were obtained.
[0030] Preparation of pH / NIR responsive cellulose nanocrystals: 2.0 g of carboxylated cellulose nanocrystals were added to a beaker containing 200.0 mL of deionized water and dispersed evenly. Then, 2.0 g of N-hydroxysuccinimide and 2.0 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added sequentially, and the mixture was magnetically stirred for 1 h to activate the carboxyl groups. Subsequently, 0.4 g of intrinsic polyaniline was dissolved in a beaker containing 500.0 mL of N-methylpyrrolidone, and then added dropwise to the activated reaction mixture. The mixture was magnetically stirred at room temperature for 24 h. After the reaction was complete, the mixture was centrifuged and washed using N-methylpyrrolidone as the washing buffer. Finally, the centrifuged product was dialyzed using deionized water as the dialysis medium and dried to obtain pH / NIR responsive cellulose nanocrystals.
[0031] S4. Preparation of pH-responsive drug-loaded cellulose nanocrystals: 1.5 g of dialdehyde cellulose nanocrystals were added to a beaker containing 400.0 mL of deionized water and dispersed evenly. Then, 4.5 g of taurine was added. The beaker was then sealed and the mixture was heated in a water bath at 55 °C and magnetically stirred in the dark for 36 h. Finally, the reaction mixture was dialyzed and dried to obtain pH-responsive drug-loaded cellulose nanocrystals.
[0032] S5. Preparation of drug-loaded micelles: 1.0 g of Pranic F68 was added to a sample vial containing 20.0 mL of deionized water and stirred to dissolve. Then, 10.0 mg of manganese pentacarbonyl bromide was added and the mixture was magnetically stirred at 300 rpm and room temperature for 24 h to obtain drug-loaded micelles loaded with manganese pentacarbonyl bromide.
[0033] S6. Preparation of pH-induced photothermal enhanced cellulose hydrogel: 70.0 mg of pH / near-infrared responsive cellulose nanocrystals were added to 9.0 mL of deionized water and dispersed evenly. Then, 420.2 mg of pH-responsive drug-loaded cellulose nanocrystals were added and stirred evenly. Subsequently, 509.8 mg of drug-loaded micelles were added to the above mixture, and the mixture was magnetically stirred at 500 rpm and room temperature for 24 h. Finally, the mixture was heated to 40 °C to evaporate the water to control the solid content of the mixture to 14.4%, thus obtaining the pH-induced photothermal enhanced cellulose hydrogel.
[0034] Example 2
[0035] S1. Preparation of carboxylated cellulose nanocrystals: 2.0 g of cellulose nanocrystals were added to an Erlenmeyer flask containing 200.0 mL of deionized water and dispersed evenly. Then, 33.3 mg of TEMPO and 666.7 mg of NaBr were added. Finally, 1.84 M and 1.2 mL of sodium hypochlorite solution were added, and the mixture was magnetically stirred at room temperature. The pH of the entire system was adjusted to 10 using sodium hydroxide, and the mixture was magnetically stirred at 600 rpm and 60 °C. After oxidation for 17 h, 6.0 mL of anhydrous ethanol was added to terminate the reaction. After washing and drying, carboxylated cellulose nanocrystals were obtained.
[0036] S2. Preparation of dialdehyde cellulose nanocrystals: 4.0 g of cellulose nanocrystals were added to an Erlenmeyer flask containing 100.0 mL of potassium hydrogen phthalate buffer solution (0.05 M, pH = 3) and stirred until homogeneous. Then, 2.4 g of sodium periodate was added, and the mixture was stirred and reacted in the dark at 37 °C for 4 h. Finally, 10.0 mL of ethylene glycol was added to the reaction mixture to terminate the reaction. After washing and drying, dialdehyde cellulose nanocrystals were obtained.
[0037] Preparation of pH / NIR responsive cellulose nanocrystals: 2.5 g of carboxylated cellulose nanocrystals were added to a beaker containing 200.0 mL of deionized water and dispersed evenly. Then, 2.5 g of N-hydroxysuccinimide and 2.5 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added sequentially, and the mixture was magnetically stirred for 1 h to activate the carboxyl groups. Subsequently, 0.5 g of intrinsic polyaniline was dissolved in a beaker containing 500.0 mL of N-methylpyrrolidone, and then added dropwise to the activated reaction mixture. The mixture was magnetically stirred at room temperature for 48 h. After the reaction was complete, the mixture was centrifuged and washed with N-methylpyrrolidone. Finally, the centrifuged product was dialyzed using deionized water as the dialysis medium and dried to obtain pH / NIR responsive cellulose nanocrystals.
[0038] S4. Preparation of pH-responsive drug-loaded cellulose nanocrystals: 2.0 g of dialdehyde cellulose nanocrystals were added to a beaker containing 400.0 mL of deionized water and dispersed evenly. Then, 6.0 g of taurine was added. The beaker was then sealed and the mixture was heated in a water bath at 60 °C and magnetically stirred in the dark for 54 h. Finally, the reaction mixture was dialyzed and dried to obtain pH-responsive drug-loaded cellulose nanocrystals.
[0039] S5. Preparation of drug-loaded micelles: 1.5 g of Pranic F68 was added to a sample vial containing 20.0 mL of deionized water and stirred to dissolve. Then, 13.0 mg of manganese pentacarbonyl bromide was added and the mixture was magnetically stirred at 300 rpm and room temperature for 24 h to obtain drug-loaded micelles loaded with manganese pentacarbonyl bromide.
[0040] S6. Preparation of pH-induced photothermal enhanced cellulose hydrogel: 85.0 mg of pH / near-infrared responsive cellulose nanocrystals were added to 9.0 mL of deionized water and dispersed evenly. Then, 448.0 mg of pH-responsive drug-loaded cellulose nanocrystals were added and stirred evenly. Subsequently, 467.0 mg of drug-loaded micelles were added to the above mixture, and the mixture was magnetically stirred at 500 rpm and room temperature for 24 h. Finally, the mixture was heated to 40 °C to evaporate the water to control the solid content of the mixture to 15.9%, thus obtaining the pH-induced photothermal enhanced cellulose hydrogel.
[0041] Example 3
[0042] S1. Preparation of carboxylated cellulose nanocrystals: 2.0 g of cellulose nanocrystals were added to an Erlenmeyer flask containing 200.0 mL of deionized water and dispersed evenly. Then, 28.5 mg of TEMPO and 666.7 mg of NaBr were added. Finally, 1.84 M and 1.2 mL of sodium hypochlorite solution were added, and the mixture was magnetically stirred at room temperature. The pH of the entire system was adjusted to 10 using sodium hydroxide, and the mixture was magnetically stirred at 600 rpm and 65 °C. After oxidation for 19 h, 6.0 mL of anhydrous ethanol was added to terminate the reaction. After washing and drying, carboxylated cellulose nanocrystals were obtained.
[0043] S2. Preparation of dialdehyde cellulose nanocrystals: 4.0 g of cellulose nanocrystals were added to an Erlenmeyer flask containing 100.0 mL of potassium hydrogen phthalate buffer solution (0.05 M, pH = 3) and stirred until homogeneous. Then, 2.8 g of sodium periodate was added, and the mixture was stirred and reacted in the dark at 39 °C for 5 h. Finally, 10.0 mL of ethylene glycol was added to the reaction mixture to terminate the reaction. After washing and drying, dialdehyde cellulose nanocrystals were obtained.
[0044] Preparation of pH / NIR responsive cellulose nanocrystals: 3.0 g of carboxylated cellulose nanocrystals were added to a beaker containing 200.0 mL of deionized water and dispersed evenly. Then, 3.0 g of N-hydroxysuccinimide and 3.0 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added sequentially, and the mixture was magnetically stirred for 1 h to activate the carboxyl groups. Subsequently, 0.6 g of intrinsic polyaniline was dissolved in a beaker containing 500.0 mL of N-methylpyrrolidone, and then added dropwise to the activated reaction mixture. The mixture was magnetically stirred at room temperature for 72 h. After the reaction was complete, the mixture was centrifuged and washed with N-methylpyrrolidone. Finally, the centrifuged product was dialyzed using deionized water as the dialysis medium and dried to obtain pH / NIR responsive cellulose nanocrystals.
[0045] S4. Preparation of pH-responsive drug-loaded cellulose nanocrystals: 2.5 g of dialdehyde cellulose nanocrystals were added to a beaker containing 400.0 mL of deionized water and dispersed evenly. Then, 7.5 g of taurine was added. The beaker was then sealed and the mixture was heated in a water bath at 65 °C and magnetically stirred in the dark for 72 h. Finally, the reaction mixture was dialyzed and dried to obtain pH-responsive drug-loaded cellulose nanocrystals.
[0046] S5. Preparation of drug-loaded micelles: 2.0 g of Pranic F68 was added to a sample vial containing 20.0 mL of deionized water and stirred to dissolve. Then, 16.0 mg of manganese pentacarbonyl bromide was added and the mixture was magnetically stirred at 300 rpm and room temperature for 24 h to obtain drug-loaded micelles loaded with manganese pentacarbonyl bromide.
[0047] S6. Preparation of pH-induced photothermal enhanced cellulose hydrogel: 100.0 mg of pH / near-infrared responsive cellulose nanocrystals were added to 9.0 mL of deionized water and dispersed evenly. Then, 465.7 mg of pH-responsive drug-loaded cellulose nanocrystals were added and stirred evenly. Subsequently, 434.3 mg of drug-loaded micelles were added to the above mixture, and the mixture was magnetically stirred at 500 rpm and room temperature for 24 h. Finally, the mixture was heated to 40 °C to evaporate the water to control the solid content of the mixture to 17.2%, thus obtaining the pH-induced photothermal enhanced cellulose hydrogel.
[0048] Performance characterization of pH-induced photothermal enhanced cellulose hydrogels prepared in Examples 1, 2, and 3
[0049] ① The pH-induced photothermal enhanced cellulose hydrogels prepared in Examples 1, 2, and 3 were tested for their temperature and hydrogen peroxide stimulation response performance. The test results all showed good temperature and hydrogen peroxide stimulation response performance. Specifically, the pH-induced photothermal enhanced cellulose hydrogel can undergo a sol-gel transition at temperatures above 33°C, making it injectable at room temperature. When injected into a simulated human body temperature environment (37°C), it can undergo in-situ gelation in response to temperature, giving it shape adaptability. Furthermore, CAY10732 was selected as a carbon monoxide fluorescent probe, and the generation of carbon monoxide by the hydrogel under hydrogen peroxide stimulation was characterized by fluorescence enhancement experiments. Specifically, in the presence of carbon monoxide, the carbon monoxide fluorescent probe detection reagent can fluoresce under excitation by a 490nm light source. The test results show that when stimulated by hydrogen peroxide, the fluorescence intensity of the carbon monoxide fluorescent probe detection reagent in the hydrogel increases with the increase of hydrogen peroxide stimulation time. After 40 min of hydrogen peroxide stimulation, the fluorescence intensity of the carbon monoxide fluorescent probe detection reagent in the hydrogels prepared in Examples 1, 2 and 3 reached 33745, 34823 and 35967 at the maximum wavelength of 515 nm, respectively, indicating that the hydrogel has the ability to generate carbon monoxide under hydrogen peroxide stimulation.
[0050] ② The pH-induced photothermal enhanced cellulose hydrogels prepared in Examples 1, 2, and 3 were subjected to pH and near-infrared light stimulation response performance tests and their pH-stimulated drug release performance was characterized. The test results all showed good pH-induced photothermal enhancement and pH-stimulated controllable drug release performance. Specifically, after 200s of near-infrared light irradiation, the hydrogel prepared in Example 1 had a higher temperature at pH=6.3 (46.9℃) than at pH=7.4 (43.0℃); the hydrogel prepared in Example 2 had a higher temperature at pH=6.3 (47.7℃) than at pH=7.4 (43.6℃); and the hydrogel prepared in Example 3 had a higher temperature at pH=6.3 (48.3℃) than at pH=7.4 (44.1℃). This indicates that the pH-induced photothermal enhanced cellulose hydrogel has good pH-induced photothermal enhancement performance, solving the problem that traditional photostimulation-responsive hydrogels are difficult to exhibit different photothermal performance under different pH conditions. Furthermore, pH-induced photothermal enhanced cellulose hydrogels can be used for drug sustained release, enabling the transport and sustained release of taurine. The drug loading capacity of the hydrogel is 160–180 mg / g. Under acidic conditions (pH = 6.8–6.3) and at 37°C, after 27 hours of drug release, the cumulative drug release at pH = 6.3 (69.13 mg / g) of the hydrogel prepared in Example 1 was higher than that at pH = 6.8 (47.87 mg / g); the cumulative drug release at pH = 6.3 (71.49 mg / g) of the hydrogel prepared in Example 2 was higher than that at pH = 6.8 (51.74 mg / g); and the cumulative drug release at pH = 6.3 (81.28 mg / g) of the hydrogel prepared in Example 3 was higher than that at pH = 6.8 (58.33 mg / g). This indicates that pH-induced photothermal enhanced cellulose hydrogels have good pH-responsive drug release controllable performance.
[0051] ③ The pH-induced photothermal enhanced cellulose hydrogels prepared in Examples 1, 2, and 3 were tested for antibacterial properties. The pH-induced photothermal enhanced cellulose hydrogels exhibited good antibacterial properties of carbon monoxide gas and photothermal synergy under near-infrared light and hydrogen peroxide stimulation. Under near-infrared light and hydrogen peroxide stimulation, the hydrogels prepared in Examples 1, 2, and 3 all had an antibacterial rate of over 99% against methicillin-resistant Staphylococcus aureus.
Claims
1. A method for preparing a pH-induced photothermal enhanced cellulose hydrogel, characterized in that, The preparation steps include the following: S1. Preparation of carboxylated cellulose nanocrystals: The hydroxyl groups on C6 of the cellulose nanocrystal structural units were oxidized to carboxyl groups by TEMPO oxidation. The degree of oxidation was controlled by adjusting the reaction conditions to prepare carboxylated cellulose nanocrystals. S2. Preparation of dialdehyde cellulose nanocrystals: Dialdehyde cellulose nanocrystals were prepared by selectively oxidizing the hydroxyl groups on C2 and C3 of the cellulose nanocrystal structural units to aldehyde groups using sodium periodate. S3. Preparation of pH / near-infrared responsive cellulose nanocrystals: pH / near-infrared responsive cellulose nanocrystals were prepared by chemically grafting intrinsic polyaniline onto the surface of carboxylated cellulose nanocrystals using an amidation reaction. S4. Preparation of pH-responsive drug-loaded cellulose nanocrystals: pH-responsive drug-loaded cellulose nanocrystals were prepared by chemically modifying the surface of dialdehyde cellulose nanocrystals with taurine using the Schiff base reaction. S5. Preparation of drug-loaded micelles: After fully dissolving Pronic F68 in deionized water, manganese pentacarbonyl bromide was added to it, and the mixture was stirred thoroughly at room temperature to prepare drug-loaded micelles; S6. Add the pH / near-infrared light-responsive cellulose nanocrystals obtained in step S3 to deionized water and disperse them evenly. Then add the pH-responsive drug-loaded cellulose nanocrystals obtained in step S4 and stir evenly. Finally, add the drug-loaded micelles obtained in step S5 to the mixture and stir thoroughly. Heat to evaporate the water to control the solid content of the product to 14.4~17.2% to obtain pH-induced photothermal enhanced cellulose hydrogel.
2. The preparation method according to claim 1, characterized in that, The main operation of step S1 is as follows: First, cellulose nanocrystals are added to deionized water and dispersed evenly. Then, TEMPO, NaBr, and sodium hypochlorite solutions are added in sequence. The mixture is then magnetically stirred at room temperature. The pH of the entire system is adjusted to 10 using sodium hydroxide. The mixture is then magnetically stirred at 55-65 °C for 15-19 h. Finally, anhydrous ethanol is added to terminate the reaction. After washing and drying, the final product is carboxylated cellulose nanocrystals. The mass ratio of cellulose nanocrystals to TEMPO is 50:1-70:
1. The mass ratio of cellulose nanocrystals to NaBr is 3:
1.
3. The preparation method according to claim 1, characterized in that, The main operation of step S2 is as follows: First, cellulose nanocrystals are added to potassium hydrogen phthalate buffer solution and stirred evenly. Then, sodium periodate is added to the solution and reacted in the dark at 35-39°C for 3-5 hours. Finally, ethylene glycol is added to the reaction mixture to end the reaction. After washing and drying, the final product is dialdehyde cellulose nanocrystals. The mass ratio of cellulose nanocrystals to sodium periodate is 2:1 to 2:1.
4.
4. The preparation method according to claim 1, characterized in that, The main operation of step S3 is as follows: First, the carboxylated cellulose nanocrystals obtained in step S1 are added to deionized water and dispersed evenly. Then, N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride are added to activate the carboxyl groups for 1 h. Subsequently, intrinsic polyaniline is dissolved in N-methylpyrrolidone and added dropwise to the activated reaction mixture, and the mixture is magnetically stirred at room temperature for 24-72 h. After the reaction, the mixture is centrifuged and washed with N-methylpyrrolidone as the washing liquid. Then, deionized water is used as the dialysis medium to dialyze the centrifuged product. After drying, the final product is pH / near-infrared responsive cellulose nanocrystals. The mass ratio of carboxylated cellulose nanocrystals, N-hydroxysuccinimide, and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride is 1:1:1, and the mass ratio of carboxylated cellulose nanocrystals to intrinsic polyaniline is 5:
1.
1.
5. The preparation method according to claim 1, characterized in that, The main operation of step S4 is as follows: First, the dialdehyde cellulose nanocrystals obtained in step S2 are added to deionized water and dispersed evenly. Then, taurine is added to the water and the mixture is magnetically stirred and reacted at 55-65°C in the dark for 36-72 hours. Finally, the product is dialyzed and freeze-dried to obtain the final product, which is pH-responsive drug-loaded cellulose nanocrystals. The mass ratio of the dialdehyde cellulose nanocrystals to taurine is 1:
3.
6. The preparation method according to claim 1, characterized in that, The mass ratio of Prönnick F68 to manganese pentacarbonyl bromide is 100:1 to 125:
1.
7. The preparation method according to claim 1, characterized in that, The mass ratio of pH / near-infrared light-responsive cellulose nanocrystals to pH-responsive drug-loaded cellulose nanocrystals is 1:4.7 to 1:6.0, and the mass ratio of pH / near-infrared light-responsive cellulose nanocrystals to drug-loaded micelles is 1:4.4 to 1:7.
3.
8. The preparation method according to claim 1, characterized in that, The heating and evaporation temperature in step S6 is 40°C.
9. The pH-induced photothermal enhanced cellulose hydrogel prepared by the preparation method according to any one of claims 1 to 8.
10. The application of the pH-induced photothermal enhanced cellulose hydrogel prepared by the preparation method according to any one of claims 1 to 8 in the preparation of a drug for treating subcutaneous abscesses; when the pH-induced photothermal enhanced cellulose hydrogel is used for the treatment of subcutaneous abscesses, it utilizes the difference in pH value between the slightly acidic environment of the subcutaneous abscess cavity (pH=6.0~6.6) and the surrounding healthy tissue (pH=7.4). Under near-infrared light and pH stimulation, the pH-induced photothermal enhanced cellulose hydrogel can endow it with photothermal properties with thermal differences under different pH environments. It can effectively perform antibacterial activity in a slightly acidic environment with pH-induced photothermal enhancement and reduce thermal damage to surrounding healthy tissues; in addition, the pH-induced photothermal enhanced cellulose hydrogel produces carbon monoxide under hydrogen peroxide stimulation to achieve an antibacterial effect, and can controllably release the anti-inflammatory drug taurine under pH stimulation; at the same time, the pH-induced photothermal enhanced cellulose hydrogel can respond to a sol-gel transition above 33°C, giving it good injectability and shape adaptability.