PH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum as well as preparation method and application of pH-sensitive composite hydrogel

Abstract

The invention belongs to the technical field of hydrogel, and particularly relates to pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum as well as a preparation method and application of the pH-sensitive composite hydrogel. Cationic guar gum (CGG) and oxidized bacterial cellulose (OBC) are used as gel wall materials, doxorubicin (DOX) is used as a loaded medicine, the CGG-OBC-DOX hydrogel is prepared through chemical crosslinking, and experimental results show that the obtained pH-sensitive hydrogel has texture characteristics of traditional hydrogel, is strong in internal crosslinking and compact in structure, and can be used for preparing the pH-sensitive hydrogel. The drug release amount at a low pH value is obviously higher than the release rate at a high pH value, and the drug release agent has relatively good pH sensitivity and slow release characteristics and can be used for preparing an intelligent drug release system; the hydrogel is prepared without adding a chemical cross-linking agent, and the process is simple, safe and non-toxic.

Description

Technical Field

[0001] The present invention belongs to the technical field of hydrogels, and more specifically, relates to a pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum, and a preparation method and application thereof. Background Art

[0002] Hydrogel is a new type of functional polymer material with a three-dimensional network structure. It can swell significantly in water, absorb and retain a large amount of water, while keeping its three-dimensional network structure intact. Hydrogel has broad application prospects in medicine, medical treatment, artificial organs and other fields due to its high water content, softness, rubber-like viscosity and good biocompatibility. However, traditional hydrogels have limitations in drug delivery, such as uncontrollable drug release rate and lack of targeting.

[0003] Guar gum, as a natural polysaccharide, is widely used in drug delivery systems due to its unique molecular structure and good water solubility. Guar gum contains a large number of hydroxyl groups on the molecular chain, which is easy to be chemically modified, thus giving the hydrogel more functionality. However, the hydrogel prepared using guar gum alone has deficiencies in mechanical strength and stability, which limits its application in the field of drug delivery.

[0004] Bacterial cellulose (BC) is a natural polymer hydrogel with excellent performance and excellent biocompatibility and mechanical strength. However, BC also has disadvantages such as poor wet strength, reduced water holding capacity and lack of antibacterial properties, which limit its further application in the field of drug delivery.

[0005] In order to overcome the above shortcomings, researchers continue to explore the functional modification of hydrogels to achieve controlled release and targeted delivery of drugs. Among them, pH-sensitive hydrogels have become one of the research hotspots because they can control the drug release rate according to the changes in pH in the body.

[0006] Chinese patent application CN110724279A discloses a method for preparing a temperature and pH-sensitive guar gum / starch composite hydrogel. The method forms a composite hydrogel by mixing guar gum, starch and other chemical reagents through a specific cross-linking reaction. The composite hydrogel not only has good temperature sensitivity and pH sensitivity, but also has high mechanical properties and stability. However, the preparation method requires the addition of cross-linking agents and other chemical reagents, which may introduce potential biosafety risks and increase preparation costs.

[0007] Therefore, developing a pH-sensitive composite hydrogel using only polysaccharides without adding cross-linking agents and other chemical reagents is of great significance for improving the safety and efficiency of drug delivery systems. Summary of the invention

[0008] The technical problem to be solved by the present invention is to overcome the defects and shortcomings of the prior art that a chemical cross-linking agent needs to be added to prepare a hydrogel, and to provide a pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum. The composite hydrogel does not require the addition of a chemical cross-linking agent, has a simple process, is safe and non-toxic, and has good pH sensitivity and sustained-release effect.

[0009] The purpose of the present invention is to provide a method for preparing the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum.

[0010] Another object of the present invention is to provide an application of the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum.

[0011] The above-mentioned purpose of the present invention is achieved through the following technical solutions:

[0012] The invention protects a pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum, which uses oxidized bacterial cellulose and cationic guar gum as gel wall materials and doxorubicin as a loaded drug, and is formed by cross-linking through Schiff base reaction between the amine groups in the oxidized bacterial cellulose and the aldehyde groups in the cationic guar gum.

[0013] The present invention uses cationic guar gum (CGG) and oxidized bacterial cellulose (OBC) as gel wall materials, doxorubicin (DOX) as a loaded drug, and prepares a composite hydrogel loaded with DOX through Schiff base chemical crosslinking. The drug release amount of the obtained hydrogel at a low pH value is significantly higher than the release rate at a high pH value, and has good pH sensitivity and sustained-release performance. Therefore, the gel can be used to prepare an intelligent drug release system, and the release of the drug can be accurately controlled according to the pH value change of the lesion site, thereby improving the treatment effect and reducing the side effects. It has broad application prospects in wound repair, inflammation treatment, etc., and can promote rapid healing and recovery of wounds.

[0014] Furthermore, the oxidized bacterial cellulose is prepared by oxidizing bacterial cellulose.

[0015] Specifically, the preparation method of oxidized bacterial cellulose includes the following steps: thoroughly mixing bacterial cellulose and a solution containing an oxidant in dark conditions, oxidizing, adding ethylene glycol to terminate the oxidation, filtering out a precipitate, adding water to wash the precipitate until it is neutral, and filtering to obtain the precipitate, which is oxidized bacterial cellulose.

[0016] Preferably, the oxidant is sodium periodate, sodium hypochlorite or hydrogen peroxide, more preferably sodium periodate.

[0017] The present invention also protects a method for preparing the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum, which comprises the following steps: mixing the bacterial cellulose solution with doxorubicin, adding the cationic guar gum thereto, mixing evenly, and fully cross-linking to obtain the composite hydrogel.

[0018] Preferably, the mass ratio of the oxidized bacterial cellulose to the cationic guar gum is 1:(0.2-1.5).

[0019] More preferably, the mass ratio of the oxidized bacterial cellulose to the cationic guar gum is 1:(0.375-0.75).

[0020] Preferably, the mass ratio of the oxidized bacterial cellulose to doxorubicin is 1:(0.001-0.2).

[0021] More preferably, the mass ratio of the oxidized bacterial cellulose to doxorubicin is 1:(0.0016-0.01).

[0022] Preferably, the concentration of the oxidized bacterial cellulose solution is 2.5-15% (w / v).

[0023] Preferably, the concentration of the cationic guar gum is 5-10% (w / v).

[0024] The present invention also protects the use of the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum in the preparation of anti-tumor drugs.

[0025] Furthermore, the tumor includes hematological tumors and solid tumors.

[0026] Furthermore, the hematological tumor includes acute leukemia or malignant lymphoma.

[0027] Furthermore, the solid tumor includes gastric cancer, breast cancer, lung cancer or ovarian cancer.

[0028] Compared with the prior art, the present invention has the following beneficial effects: the present invention prepares a pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum for gastrointestinal targeted delivery system. Specifically, cationic guar gum (CGG) and oxidized bacterial cellulose (OBC) are used as gel wall materials, doxorubicin (DOX) is used as the loaded drug, and CGG-OBC-DOX hydrogel is prepared by chemical crosslinking. The mechanical properties of the hydrogel are studied by a texture analyzer, and the effect of doxorubicin (DOX) as a model drug released from the hydrogel is studied by an in vitro simulated gastrointestinal model. The texture results show that the texture characteristics of different OBC addition amounts are different. In vitro simulated gastrointestinal experiments show that the drug release amount at low pH values ​​is significantly higher than the release rate at high pH values, and it has good pH sensitivity and sustained release performance. Therefore, the gel can be used to prepare an intelligent drug release system, accurately control the release of the drug according to the pH change of the lesion site, improve the therapeutic effect, reduce side effects, and has broad application prospects in wound repair, inflammation treatment, etc., and can promote rapid healing and recovery of wounds; and the preparation of the hydrogel does not require the addition of chemical crosslinking agents, the process is simple, safe and non-toxic. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 From left to right, the appearance pictures of blank hydrogels CGG-OBC (0%), CGG-OBC (2.5%), CGG-OBC (5%), CGG-OBC (10%), and CGG-OBC (15%) prepared by Comparative Example 1, Example 2, Example 1, Example 3, and Example 4 are shown.

[0030] Figure 2 for Figure 1 From left to right, the appearance of DOX-loaded CGG-OBC-DOX (0%), CGG-OBC-DOX (2.5%), CGG-OBC-DOX (5%), CGG-OBC-DOX (10%), and CGG-OBC-DOX (15%) hydrogels prepared in Example 1, Example 2, Example 1, Example 3, and Example 4 are shown.

[0031] Figure 3 FTIR spectra of blank hydrogels prepared in Examples 1 to 4 and Comparative Example 1.

[0032] Figure 4 From A to E in the figure are the statistical graphs of the release curves of CGG-OBC-DOX (0%), CGG-OBC-DOX (2.5%), CGG-OBC-DOX (5%), CGG-OBC-DOX (10%), and CGG-OBC-DOX (15%) hydrogels at pH = 2.0, pH = 5.5, and pH = 7.4, respectively.

[0033] Figure 5 Statistical graph of release curve data of CGG-OBC-DOX (5%) and CGG-BC-DOX hydrogel at pH = 2.0, pH = 5.5, and pH = 7.4.

[0034] Figure 6 It is a statistical diagram of the drug release effect of the hydrogels loaded with different drugs obtained in Comparative Examples 5 to 7, where A, B, and C are the release effects of β-carotene, curcumin, and levofloxacin, respectively.

[0035] Figure 7 Statistical graph of the release curves of doxorubicin (DOX) in the gastrointestinal environment of CGG-OBC-DOX (0%), CGG-OBC-DOX (2.5%), CGG-OBC-DOX (5%), CGG-OBC-DOX (10%), and CGG-OBC-DOX (15%).

[0036] Figure 8 Texture analysis diagrams of blank hydrogels CGG-OBC (0%), CGG-OBC (2.5%), CGG-OBC (5%), CGG-OBC (10%), and CGG-OBC (15%). AF represent hardness, cohesion, stickiness, chewiness, resilience, and elasticity, respectively. DETAILED DESCRIPTION

[0037] The present invention is further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0038] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0039] Cationic guar gum was purchased from Shandong Yousuo Chemical Technology Co., Ltd.

[0040] Ordinary guar gum was purchased from Shanghai MacLean Biochemical Technology Co., Ltd.

[0041] Bacterial cellulose was purchased from Hainan Yide Food Co., Ltd.

[0042] Doxorubicin hydrochloride (purity 98%) was purchased from Shanghai MacLean Biochemical Technology Co., Ltd.

[0043] Levofloxacin was purchased from Shanghai McLean Biochemical Technology Co., Ltd.

[0044] β-Carotene was purchased from Shanghai MacLean Biochemical Technology Co., Ltd.

[0045] Curcumin was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0046] Example 1 pH-sensitive composite hydrogel based on bacterial cellulose / cationic guar gum (OBC concentration is 5%)

[0047] (1) Oxidation of bacterial cellulose (BC)

[0048] Add 50 mL of 20% ethanol solution to 0.5 g of dry BC powder and homogenize it for 2 to 3 minutes until it forms a homogeneous phase. Then add NaIO4 solution to the above BC solution and stir it in the dark for 2 hours. Finally, add 0.6 g of ethylene glycol solution to the reaction system, continue stirring for 5 minutes to terminate the oxidation reaction, and finally take out the rotor. Centrifuge the reactant and remove the supernatant. Add 20 mL of water, vortex for 2 minutes, centrifuge for 5 minutes, remove the supernatant, and repeat the operation until the pH of the solution is neutral. The resulting product is freeze-dried to obtain oxidized bacterial cellulose (OBC).

[0049] (2) Preparation of composite hydrogel (OBC concentration 5%)

[0050] A 5% (w / v) OBC solution was prepared with PBS (0.01M, 7.4) solution, homogenized at 15000rpm for 1min, 0.5mg DOX was weighed in advance in the mold, and then 2mL OBC solution was weighed in the mold, stirred to make it evenly dispersed in the system, and then 0.075g CGG was slowly added and stirred continuously to form a uniform hydrogel CGG-OBC-DOX (5%). The blank hydrogel CGG-OBC (5%) was operated in the same manner except that DOX was not added.

[0051] Example 2 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum (OBC concentration of 2.5%)

[0052] The difference from step (2) in Example 1 is that the OBC concentration is 2.5% (w / v), and the other conditions and parameters are the same. The obtained hydrogel is referred to as CGG-OBC-DOX (2.5%).

[0053] The blank hydrogel CGG-OBC (2.5%) was prepared in the same manner except that doxorubicin was not added.

[0054] Example 3 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum (OBC concentration of 10%)

[0055] The difference from step (2) in Example 1 is that the OBC concentration is 10% (w / v), and the other conditions and parameters are the same. The obtained hydrogel is referred to as CGG-OBC-DOX (10%).

[0056] The blank hydrogel CGG-OBC (10%) was prepared in the same manner except that doxorubicin was not added.

[0057] Example 4 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum (OBC concentration of 15%)

[0058] The difference from step (2) in Example 1 is that the OBC concentration is 15% (w / v), and the other conditions and parameters are the same. The obtained hydrogel is referred to as CGG-OBC-DOX (15%).

[0059] The blank hydrogel CGG-OBC (15%) was prepared in the same manner except that doxorubicin was not added.

[0060] Comparative Example 1 Cationic guar gum-based hydrogel (OBC concentration is 0%)

[0061] 0.5 mg of DOX was weighed in advance in the mold, and then 2 mL of PBS solution was added to the mold and stirred to evenly disperse it in the system. Then 0.075 g of CGG was slowly added and stirred continuously to form a uniform hydrogel, referred to as CGG-OBC-DOX (0%).

[0062] The obtained hydrogel of blank hydrogel is referred to as CGG-OBC (0%). Except for not adding doxorubicin, the other steps are the same. Comparative Example 2 pH-sensitive composite hydrogel based on bacterial cellulose / cationic guar gum

[0063] The difference from step (2) in Example 1 is that the oxidized bacterial cellulose is replaced by an equal amount of bacterial cellulose, and the other conditions and parameters are the same.

[0064] Comparative Example 3 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / guar gum

[0065] The difference from step (2) in Example 1 is that the cationic guar gum is replaced with an equal amount of ordinary guar gum, and the other conditions and parameters are the same.

[0066] The obtained mixture is a pasty mixture and cannot form a hydrogel. On this basis, increasing or decreasing the amount of common guar gum cannot form a hydrogel.

[0067] Comparative Example 4 pH-sensitive composite hydrogel based on bacterial cellulose / chitosan

[0068] The difference from step (2) in Example 1 is that the cationic guar gum is replaced with an equal amount of chitosan, and the other conditions and parameters are the same.

[0069] The obtained mixture is a paste, which cannot form a hydrogel. On this basis, increasing or decreasing the amount of chitosan, hydrogel cannot be formed. This is because solid hydrogel needs to form a stable solid shape, and other wall materials cannot form a stable bond with CGG when added, but instead destroy the hydrogen bond of CGG itself, hindering the effect of gel formation. Therefore, Comparative Example 1 can form a stable hydrogel, while Comparative Examples 3 and 4 cannot form a hydrogel after adding unsuitable wall materials.

[0070] Comparative Example 5 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum (loaded with β-carotene)

[0071] The difference from step (2) in Example 1 is that the loaded doxorubicin is replaced with an equal amount of β-carotene, and the other conditions and parameters are the same.

[0072] Comparative Example 6 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum (loaded with curcumin)

[0073] The difference from step (2) in Example 1 is that the loaded doxorubicin is replaced with an equal amount of curcumin, and the other conditions and parameters are the same.

[0074] Comparative Example 7 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum (loaded with levofloxacin)

[0075] The difference from step (2) in Example 1 is that the loaded doxorubicin is replaced with an equal amount of levofloxacin, and the other conditions and parameters are the same.

[0076] Experimental Example 1 Appearance of hydrogels prepared with different OBC concentrations

[0077] The hydrogels prepared in Examples 1 to 4 and Comparative Example 1 were photographed. The results are as follows: Figures 1-2 As shown, Figure 1 From left to right, they are CGG-OBC (0%), CGG-OBC (2.5%), CGG-OBC (5%), CGG-OBC (10%), and CGG-OBC (15%); Figure 2 From left to right are CGG-DOX, CGG-OBC-DOX (2.5%), CGG-OBC-DOX (5%), CGG-OBC-DOX (10%), and CGG-OBC-DOX (15%). As can be seen from the figure, the bubbles in the gel decrease with the increase of OBC concentration, and the texture of the gel gradually becomes firmer from soft.

[0078] Experimental Example 2 Chemical structure of hydrogel

[0079] The blank hydrogel samples obtained in Examples 1 to 4 and Comparative Example 1 were placed in a refrigerator for pre-freezing for 24 hours and then placed in a freeze dryer for freeze drying for 48 hours. The freeze-dried samples were analyzed using an infrared spectrometer with a scanning range of 4000-400 cm -1 , scanned 16 times, with a resolution of 4cm -1 . Obtain the infrared spectrum of the hydrogel sample.

[0080] The results are as follows Figure 3 As shown, about 2904cm -1 The characteristic peak at 1641 cm is due to the stretching vibration of the internal alkyl segment -CH2-. The stretching vibration peak of the C=O of the amide group appears at 1641 cm -1 The stretching vibration between NH and OH is at 3308 cm -1 Taking the blank hydrogel CGG-OBC (5%) prepared in Example 1 as an example, the stretching vibration peak of the C=O of the amide group is at 1641 cm -1 At 3308cm -1 Because of the stretching vibration between NH and OH, hydrogen bonds are formed, so the absorption peak width is relatively large.

[0081] Experimental Example 3: Study on drug release of hydrogel at different pH

[0082] (1) Drug release of hydrogels prepared with different OBC concentrations at different pH values

[0083] Weigh 0.2 g of the hydrogel loaded with DOX in Examples 1 to 4 and Comparative Example 1, add 4 mL of an equal volume of an aqueous solution of pH = 2.0, pH = 5.5, and pH = 7.4, respectively, shake at 37 ° C, 150 rpm, and take out 200 μL at 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, and 6 h, set parallel, measure the absorbance, and then add the corresponding volume of liquid back to the system. Record the absorbance of the liquid taken out at different times at 480 nm and calculate the percentage of drug release, and draw the time-drug release curve at different pH.

[0084] The results are as follows Figure 4As shown in the figure, from A to E are the release curves of CGG-DOX (0%), CGG-OBC-DOX (2.5%), CGG-OBC-DOX (5%), CGG-OBC-DOX (10%), and CGG-OBC-DOX (15%) hydrogels under different pH environmental conditions. It is obvious from the figure that from the experimental results, the drug release of the hydrogel sample without adding OBC does not have good pH sensitivity, while the DOX drug release of the hydrogel with added OBC is regular. With the increase of environmental pH, the sustained release time of DOX decreases, and the cumulative release rate of DOX also decreases. Among them, the system CGG / OBC (10%) / DOX has good pH sensitivity and can better release DOX in the environment of pH = 2.0 and pH = 5.5. In general, all hydrogels with added OBC can show drug-sensitive release in the environment of pH = 2.0 and pH = 7.4, and always release more and more completely in the environment of pH = 2.0.

[0085] (2) Drug release of hydrogels prepared with different wall materials at different pH values

[0086] Accurately weigh 0.2g of the hydrogel obtained in Example 1 and Comparative Example 2 in a glass bottle, and add 4mL of solutions with pH values ​​of 2.0, 5.5, and 7.4, respectively, shake at 37°C and 150rpm, and take out 200vL at 1h, 2h, 3h, 4h, 5h, and 6h, set in parallel, measure the absorbance of the corresponding drugs at the corresponding strongest absorption wavelength, and then add the corresponding volume of liquid back to the system. Record the absorbance of the liquid taken out at different times at the characteristic absorption wavelength of the corresponding drug, and draw the time-drug release curve at different pH values.

[0087] The results are as follows Figure 5 As shown in the figure, it can be seen that the hydrogel formed by oxidatively modified OBC has obvious pH-sensitive drug release properties, while the hydrogel formed by unmodified BC has weak pH-sensitive drug release properties and does not have good selective release. From the perspective of drug sustained release, the hydrogel formed by oxidatively modified OBC has excellent sustained release effect, which can be maintained within 6 hours. In contrast, the drug sustained release effect of the hydrogel formed by unmodified BC is poor, and the drug release rate gradually weakens after 3-4 hours.

[0088] (3) Drug release of hydrogels loaded with different drugs at different pH values

[0089] Accurately weigh 0.2g of the drug-loaded hydrogels of Comparative Examples 5 to 7 in glass bottles, and add 4mL of solutions with pH values ​​of 2.0, 5.5, and 7.4, respectively, shake at 37°C and 150rpm, and take out 200μL at 1h, 2h, 3h, 4h, 5h, and 6h, set in parallel, measure the absorbance of the corresponding drugs at the corresponding strongest absorption wavelength, and then add the corresponding volume of liquid back to the system. Record the absorbance of the liquid taken out at different times at the characteristic absorption wavelength of the corresponding drug, and draw the time-drug release curve at different pH values.

[0090] The results are as follows Figure 6 As shown in the figure above, it can be seen that the release effect of CGG-OBC hydrogel on two oil-soluble drugs, β-carotene and curcumin, is poor, and the release effect on levofloxacin is better than the other two drugs, but the release amount of the drug exceeds 50% within one hour, and the initial release amount is too high. The above results show that CGG-OBC hydrogel has selective pH-sensitive sustained release of drugs.

[0091] Experimental Example 4: Simulating the in vivo gastrointestinal environment for drug release

[0092] Take the hydrogels loaded with DOX in Examples 1 to 4 and Comparative Example 1 and soak them in a pH=2.0 HCl solution (simulating the environment of DOX entering the stomach) for 0h-4h, and soak them in a pH=7.4 PBS buffer (simulating the environment of DOX entering the intestine) for 4-8h, take out the liquid at 0.5h, 1h, 2h, 3h, 4h, 5h, 6h, 7h, and 8h to measure the absorbance, and then add the corresponding volume of acid and alkali solution to the system to ensure that the overall system remains unchanged. Set up a set of parallel experiments.

[0093] The results are as follows Figure 7 As shown, the hydrogel was placed in a medium with a pH of 2.0 for 0-4h, and the cumulative release of DOX gradually increased with time; the hydrogel was placed in a liquid environment with a pH of 7.4 for 4-8h, and the cumulative release of DOX also gradually increased with time, but the increase was small. From the above results, it can be seen that the drug release amount and release rate of the hydrogel samples obtained in Examples 1 to 4 at low pH values ​​are significantly higher than the drug release at high pH values, and have good pH sensitivity and sustained release effect. Therefore, the gel can be used to prepare an intelligent drug release system, which can accurately control the release of drugs according to the pH changes in the lesion site, improve the therapeutic effect, and reduce side effects. However, the OGG-DOX obtained in Comparative Example 1 has no sustained release function under acidic conditions, and is released in large quantities from the beginning, and the release amount in 1h reaches more than 50%.

[0094] Experimental Example 5 Texture Test

[0095] The texture analysis was performed on the blank hydrogels obtained in Examples 1 to 4 and Comparative Example 1. The texture distribution analysis (TPA) of the hydrogel was measured by a texture analyzer. A P / 36R probe was used, the pre-test speed was 1.50 mm / sec, the test speed was 1.00 mm / sec, the post-test speed was 1.00 mm / sec, the distance was 15.00 mm, and the trigger force was 2.0 g.

[0096] The results are as follows Figure 8 As shown, hardness, cohesion, stickiness, chewiness, resilience, and elasticity can represent the mechanical properties of the hydrogel samples. There is a close relationship between the texture data. From the experimental results, hardness is inversely proportional to elasticity, that is, objects with high hardness have low elasticity. The elasticity, cohesion, and resilience of the hydrogel with 5% OBC added are the best, indicating that the mechanical strength of the internal structure of the hydrogel is good. The hardness, stickiness, and chewiness of the blank hydrogel are relatively high, indicating that the stress required to deform it to a certain deformation is greater.

[0097] The texture analysis results of DOC-loaded hydrogels were basically the same as those of their corresponding blank hydrogels.

[0098] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum, characterized in that: Oxidized bacterial cellulose and cationic guar gum are used as gel wall materials, doxorubicin is used as the loaded drug, and the gel is formed by cross-linking of the amine groups in the oxidized bacterial cellulose and the aldehyde groups in the cationic guar gum through Schiff base reaction.

2. The pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum according to claim 1, characterized in that: The oxidized bacterial cellulose is prepared by oxidizing bacterial cellulose.

3. The pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum according to claim 2, characterized in that: The preparation method of oxidized bacterial cellulose comprises the following steps: fully mixing bacterial cellulose and a solution containing an oxidant in dark conditions, oxidizing, adding ethylene glycol to terminate the oxidation, filtering to obtain a precipitate, adding water to wash the precipitate until it is neutral, and filtering to obtain the precipitate, which is oxidized bacterial cellulose.

4. The pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum according to claim 3, characterized in that: The oxidant is sodium periodate, sodium hypochlorite or hydrogen peroxide.

5. The method for preparing the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum according to any one of claims 1 to 4, characterized in that: The method comprises the following steps: mixing oxidized bacterial cellulose solution and doxorubicin, adding cationic guar gum therein, mixing evenly, and fully cross-linking to obtain the product.

6. The preparation method according to claim 5, characterized in that: The mass ratio of the oxidized bacterial cellulose to the cationic guar gum is 1:(0.2-1.5).

7. The preparation method according to claim 5, characterized in that: The mass ratio of the oxidized bacterial cellulose to doxorubicin is 1:(0.001-0.2).

8. The preparation method according to claim 5, characterized in that: The concentration of the oxidized bacterial cellulose solution is 2.5-15% (w / v).

9. The preparation method according to claim 8, characterized in that: The concentration of the oxidized bacterial cellulose is 5-10% (w / v).

10. Use of the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum according to any one of claims 1 to 4 in the preparation of anti-tumor drugs.

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