Oxidized bacterial cellulose / cationic guar gum-based pH-sensitive composite hydrogel and preparation method and application thereof

Abstract

The application belongs to the technical field of hydrogel, and particularly relates to a pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum and a preparation method and application thereof. The application takes cationic guar gum (CGG) and oxidized bacterial cellulose (OBC) as gel wall materials, and takes adriamycin (DOX) as a loaded drug, and a CGG-OBC-DOX hydrogel is prepared through chemical cross-linking. Experimental results show that the obtained pH-sensitive hydrogel has the texture characteristics of traditional hydrogel, the internal cross-linking is strong, the structure is compact, the drug release amount at a low pH value is obviously higher than the release rate at a high pH value, the pH sensitivity and the slow release characteristics are good, the pH-sensitive hydrogel can be used for preparing an intelligent drug release system, and the hydrogel preparation does not need to add a chemical cross-linking agent, the process is simple, safe and non-toxic.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of hydrogel. More specifically, it relates to a pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum and its preparation method and application. BACKGROUND

[0002] Hydrogel is a new type of functional polymer material with a three-dimensional network structure. It can significantly swell in water, absorb and retain a large amount of water, and at the same time maintain its three-dimensional network structure without being destroyed. Due to its high water content, softness, rubber-like viscosity and good biocompatibility, hydrogel has wide application prospects in the fields of medicine, medical treatment, artificial organs, etc. However, traditional hydrogels have limitations in drug delivery, such as uncontrollable drug release rate, lack of targeting, etc.

[0003] Guar gum, as a natural polysaccharide, is widely used in drug delivery systems due to its unique molecular structure and good water solubility. The molecular chain of guar gum contains a large number of hydroxyl groups, which are easy to be chemically modified, thereby endowing the hydrogel with more functionality. However, the hydrogel prepared by using guar gum alone has shortcomings 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, which has excellent biocompatibility and mechanical strength. However, bacterial cellulose also has the shortcomings of poor wet strength, decreased 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-mentioned shortcomings, researchers have been exploring the functional modification of hydrogel to achieve controlled release and targeted delivery of drugs. Among them, pH-sensitive hydrogel has become one of the research hotspots because it can control the drug release rate according to the change of pH value in the body.

[0006] Chinese patent application CN110724279A discloses a preparation method of temperature and pH-sensitive guar gum / starch composite hydrogel. The method mixes guar gum, starch and other chemical reagents, and forms a composite hydrogel through a specific crosslinking reaction. The composite hydrogel not only has good temperature sensitivity and pH sensitivity, but also has high mechanical properties and stability. However, this preparation method needs to add crosslinking agent and other chemical reagents, which may introduce potential biological safety risks and increase the preparation cost.

[0007] Therefore, it is of great significance to develop a composite hydrogel with pH sensitivity by using polysaccharide substances only without adding crosslinking agent and other chemical reagents, in order to improve the safety and efficiency of drug delivery systems. SUMMARY

[0008] The technical problem solved by the present application is to overcome the defects and deficiencies of the prior art in preparing hydrogel by adding chemical crosslinking agent, and to provide a pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum, which does not need to add chemical crosslinking 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 application is to provide a preparation method of the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum.

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

[0011] The above purposes of the present application are achieved by the following technical solutions.

[0012] The present application 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 material, and uses doxorubicin as loaded drug, and is crosslinked by Schiff base reaction between amine groups in oxidized bacterial cellulose and aldehyde groups in cationic guar gum.

[0013] The present application uses cationic guar gum (CGG) and oxidized bacterial cellulose (OBC) as gel wall material, and doxorubicin (DOX) as loaded drug, and is prepared into a composite hydrogel loaded with DOX by Schiff base chemical crosslinking. The drug release amount of the obtained hydrogel at low pH value is obviously higher than the release rate at high pH value, and the hydrogel has good pH sensitivity and sustained release performance. Therefore, the hydrogel can be used for preparing an intelligent drug release system, accurately controlling the release of drugs according to the pH value change of the lesion site, improving the treatment effect, reducing side effects, and having a wide application prospect in wound repair, inflammation treatment and the like, and can promote the rapid healing and recovery of wounds.

[0014] Further, the oxidized bacterial cellulose is prepared from bacterial cellulose by oxidation.

[0015] Specifically, the preparation method of the oxidized bacterial cellulose comprises the following steps: fully mixing bacterial cellulose and a solution containing an oxidizing agent under dark conditions, oxidizing, adding ethylene glycol to terminate oxidation, filtering to obtain a precipitate, washing the precipitate with water until neutral, and suction filtering. The obtained precipitate is the oxidized bacterial cellulose.

[0016] Preferably, the oxidizing agent is sodium periodate, sodium hypochlorite or hydrogen peroxide. More preferably, it is sodium periodate.

[0017] The application also protects a preparation method of the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum, comprising the following steps: mixing a bacterial cellulose solution with adriamycin, adding cationic guar gum thereto, mixing uniformly, and fully cross-linking to obtain the product.

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

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

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

[0021] More preferably, the mass ratio of the oxidized bacterial cellulose and the adriamycin 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 application also protects an application of the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum in the preparation of an antitumor drug.

[0025] Further, the tumor includes a hematological tumor and a solid tumor.

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

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

[0028] Compared with the prior art, the present application has the following beneficial effects: the present application prepares a pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum for a gastrointestinal targeting delivery system. Specifically, cationic guar gum (CGG) and oxidized bacterial cellulose (OBC) are used as gel wall materials, doxorubicin (DOX) is used as a loaded drug, CGG-OBC-DOX hydrogel is prepared by chemical crosslinking, the mechanical properties of the hydrogel are studied by using a texture analyzer, and the release effect of doxorubicin (DOX) as a model drug from the hydrogel is studied by simulating the gastrointestinal model in vitro. The texture results show that the texture characteristics of different OBC addition amounts are different. The in vitro simulation of the gastrointestinal tract shows that the drug release amount at low pH is significantly higher than the release rate at high pH, and the hydrogel has good pH sensitivity and sustained release performance, so the gel can be used to prepare an intelligent drug release system, accurately control the release of the drug according to the pH value of the lesion site, improve the treatment effect, reduce the side effects, and has a wide application prospect in wound repair, inflammation treatment and the like, and can promote the rapid healing and recovery of the wound; and the preparation of the hydrogel does not need to add a chemical crosslinking agent, the process is simple, safe and non-toxic. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 The appearance diagram of the blank hydrogel CGG-OBC (0%), CGG-OBC (2.5%), CGG-OBC (5%), CGG-OBC (10%), and CGG-OBC (15%) prepared from left to right in Comparative Example 1, Example 2, Example 1, Example 3, and Example 4.

[0030] Figure 2 For Figure 1 The appearance diagram of the CGG-OBC-DOX (0%), CGG-OBC-DOX (2.5%), CGG-OBC-DOX (5%), CGG-OBC-DOX (10%), and CGG-OBC-DOX (15%) hydrogel loaded with DOX prepared from left to right in Comparative Example 1, Example 2, Example 1, Example 3, and Example 4.

[0031] Figure 3 The FTIR spectrum of the blank hydrogel prepared in Examples 1-4 and Comparative Example 1.

[0032] Figure 4 From A to E are the release curve data statistics diagram of the CGG-OBC-DOX (0%), CGG-OBC-DOX (2.5%), CGG-OBC-DOX (5%), CGG-OBC-DOX (10%), and CGG-OBC-DOX (15%) hydrogel at pH=2.0, pH=5.5, and pH=7.4.

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

[0034] Figure 6 Statistical diagram of release effect of hydrogel loaded with different drugs obtained in Comparative Examples 5-7 on drugs, A, B, and C represent the release effect of β-carotene, curcumin, and levofloxacin, respectively.

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

[0036] Figure 8 Texture analysis diagram of blank hydrogel CGG-OBC (0%), CGG-OBC (2.5%), CGG-OBC (5%), CGG-OBC (10%), and CGG-OBC (15%), A-F represent hardness, cohesiveness, gumminess, chewiness, resilience, and springiness, respectively. DETAILED DESCRIPTION

[0037] The present application will be further described in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present application in any form. Unless otherwise specified, the reagents, methods, and equipment used in the present application are conventional reagents, methods, and equipment in the technical field.

[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] Common guar gum was purchased from Shanghai Maikelin Biochemical Technology Co., Ltd.

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

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

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

[0044] β-carotene was purchased from Shanghai Maikelin 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 5%)

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

[0048] 0.5 g of dry BC powder was added to 50 mL of 20% ethanol solution and homogenized for 2-3 min until it formed a homogeneous solution. NaI04solution was then added to the BC solution and stirred in the dark for 2 hours. Finally, 0.6 g of ethylene glycol solution was added to the reaction system and stirring was continued for 5 min to terminate the oxidation reaction, and the rotor was finally removed. The reaction was centrifuged and the supernatant was removed. Another 20 mL of water was added, vortexed for 2 min, centrifuged for 5 min, and the supernatant was removed and the operation was repeated until the solution pH was neutral. The resulting product was 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 (0.01 M, 7.4) solution, homogenized at 15000 rpm for 1 min, and 0.5 mg of DOX was weighed in advance in the mold, then 2 mL of OBC solution was weighed in the mold, stirred to disperse uniformly in the system, then 0.075 g of CGG was slowly added and stirred constantly to form a uniform hydrogel CGG-OBC-DOX (5%).

[0051] Example 2 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum (OBC concentration 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 resulting hydrogel is referred to as CGG-OBC-DOX (2.5%).

[0053] The blank hydrogel CGG-OBC (2.5%) is consistent with the other steps except that no doxorubicin is added.

[0054] Example 3 pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum (OBC concentration 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 resulting hydrogel is referred to as CGG-OBC-DOX (10%).

[0056] Blank hydrogel CGG-OBC (10%). Except that no doxorubicin was added, other steps were consistent.

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

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

[0059] Blank hydrogel CGG-OBC (15%). Except that no doxorubicin was added, other steps were consistent.

[0060] Comparative Example 1 Hydrogel based on cationic guar gum (OBC concentration was 0%)

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

[0062] Blank hydrogel The obtained hydrogel was referred to as CGG-OBC (0%). Except that no doxorubicin was added, other steps were consistent.

[0063] The difference from step (2) in Example 1 was that the oxidized bacterial cellulose therein was replaced with an equal amount of bacterial cellulose, and other conditions and parameters were 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 was that the cationic guar gum therein was replaced with an equal amount of ordinary guar gum, and other conditions and parameters were the same.

[0066] The obtained was a paste-like mixture and could not form a hydrogel. On this basis, increasing or decreasing the amount of ordinary guar gum could not 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 was that the cationic guar gum therein was replaced with an equal amount of chitosan, and other conditions and parameters were the same.

[0069] The obtained mixture was paste-like and could not form a hydrogel. Increasing or decreasing the amount of chitosan could not form a hydrogel. This is because a solid hydrogel needs to form a stable solid shape, and other wall materials added cannot form a stable bond with CGG, but instead destroy the hydrogen bonds of CGG itself, hindering the effect of gel formation. Therefore, Comparative Example 1 can form a stable hydrogel, and Comparative Examples 3 and 4 added unsuitable wall materials and could not form a hydrogel.

[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 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 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 other conditions and parameters are the same.

[0076] Appearance of hydrogels prepared with different OBC concentrations

[0077] The hydrogels prepared in Examples 1-4 and Comparative Example 1 were photographed, and the results are shown in Figures 1-2 Figure 1 From left to right 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 of the gel decrease with increasing OBC concentration, and the texture of the gel gradually becomes more firm.

[0078] Chemical structure of hydrogel

[0079] ​The blank hydrogel samples obtained in Examples 1-4 and Comparative Example 1 were pre-frozen in a refrigerator for 24 h and then freeze-dried in a freeze dryer for 48 h. The freeze-dried samples were analyzed by an infrared spectrometer with a scanning range of 4000-400 cm -1 , 16 scans and a resolution of 4 cm -1 . The infrared spectra of the hydrogel samples were obtained.

[0080] The results are shown in Figure 3 . The characteristic peak at about 2904 cm -1 was due to the stretching vibration of the internal alkyl chain segment -CH2-, the stretching vibration peak of the amide group C=O was at 1641 cm -1 , and the stretching vibration between N-H and O-H was at about 3308 cm -1 . Taking the blank hydrogel CGG-OBC (5%) prepared in Example 1 as an example, the stretching vibration peak of the amide group C=O was at 1641 cm -1 , and the stretching vibration between N-H and O-H was at about 3308 cm -1 , forming a hydrogen bond association, so the absorption peak was wide.

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

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

[0083] An equal amount of 0.2 g of the DOX-loaded hydrogels of Examples 1-4 and Comparative Example 1 was weighed, and an equal volume of 4 mL of an aqueous solution with pH = 2.0, pH = 5.5, and pH = 7.4 was added, respectively, and shaken at 37°C and 150 rpm. 200 μL was taken out at 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, and 6 h, and parallel settings were made, and the absorbance was measured, and then the corresponding volume of liquid was added back to the system. The absorbance of the liquid taken out at different times at 480 nm was recorded, and the drug release percentage was calculated, and the time-drug release curves at different pH were plotted.

[0084] The results are shown in Figure 4As shown, 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%), CGG-OBC-DOX (15%) hydrogels under different pH conditions. As can be seen from the figure, from the experimental results, the drug release of the hydrogel sample without OBC does not have good pH sensitivity, while the DOX drug release of the hydrogel with OBC has regularity, and with the increase of the environmental pH, the slow 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 sensitive characteristics, and can better release DOX in the environment of pH=2.0 and pH=5.5. In general, all the hydrogels with 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 under different pH

[0086] Accurately weigh 0.2 g of the hydrogel obtained in Example 1 and Comparative Example 2 in a glass bottle, respectively, and add 4 mL of solution with pH of 2.0, 5.5 and 7.4, respectively, and oscillate at 37°C and 150 rpm, and take out 200 vL at 1h, 2h, 3h, 4h, 5h, 6h, set parallel, and measure the absorbance of the corresponding different drugs at the corresponding strongest absorption wavelength, and then add the corresponding volume of liquid 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 under different pH.

[0087] The results are shown in Figure 5 As can be seen from the figure, the hydrogel formed by the oxidized OBC has obvious pH sensitive drug release properties, while the hydrogel formed by the unmodified BC has weak pH sensitive drug release properties and does not have good selective release. From the effect of drug slow release, the hydrogel formed by the oxidized OBC has excellent slow release effect, which can maintain the slow release effect for 6h, while the drug slow release effect of the hydrogel formed by the unmodified BC is poor, and the drug release rate is slowly weakened after 3-4h.

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

[0089] Accurately weigh 0.2 g of the drug-loaded hydrogel of Comparative Example 5-7 in a glass bottle, and add 4 mL of a solution with pH of 2.0, 5.5, and 7.4, respectively, and oscillate at 37°C and 150 rpm, and take out 200 μL at 1 h, 2 h, 3 h, 4 h, 5 h, and 6 h, set up parallel experiments, and measure the absorbance of the corresponding drug at the corresponding strongest absorption wavelength, and then add back the corresponding volume of liquid 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.

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

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

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

[0093] The results are shown in Figure 7 As shown in the above results, the cumulative release amount of DOX gradually increases with time when the hydrogel is placed in a medium with pH = 2.0 for 0-4 h, and the cumulative release amount of DOX also gradually increases with time when the hydrogel is placed in a liquid environment with pH = 7.4 for 4-8 h, but the increase is smaller. From the above results, it can be seen that the drug release amount and release rate of the hydrogel samples obtained in Examples 1-4 are significantly higher at low pH than at high pH, and have good pH sensitivity and slow release effect. Therefore, the gel can be used to prepare an intelligent drug release system, accurately control the release of drugs according to the pH value of the lesion site, improve the treatment effect, and reduce side effects. The OGG-DOX obtained in Comparative Example 1 does not have a slow release function under acidic conditions, and releases a large amount of drug at the beginning, with a release amount of more than 50% at 1 h.

[0094] Experimental Example 5: Texture test

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

[0096] The results are as follows Figure 8 As shown, hardness, cohesiveness, adhesiveness, chewiness, resilience, and elasticity can represent the mechanical properties of hydrogel samples. There is a close relationship between the textural data; the experimental results show that hardness is inversely proportional to elasticity, meaning that objects with high hardness have low elasticity. The hydrogel with 5% OBC exhibits the best elasticity, cohesiveness, and resilience, indicating good mechanical strength due to the adhesion of its internal structure. The blank hydrogel has higher values ​​for hardness, adhesiveness, and chewiness, indicating that greater stress is required to deform it to a certain extent.

[0097] The textural analysis results of the DOC-loaded hydrogel were basically the same as those of its corresponding blank hydrogel.

[0098] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. An oxidized bacterial cellulose / cationic guar-based pH-sensitive composite hydrogel, characterized in that, The gel wall material is oxidized bacterial cellulose and cationic guar gum, and the loaded drug is doxorubicin; the gel is crosslinked by Schiff base reaction between amine groups in the oxidized bacterial cellulose and aldehyde groups in the cationic guar gum; the mass ratio of the oxidized bacterial cellulose to the cationic guar gum is 1: (0.2-1.5).

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 from bacterial cellulose by oxidation.

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 the oxidized bacterial cellulose comprises the following steps: mixing bacterial cellulose and a solution containing an oxidizing agent in dark conditions, performing oxidation, adding ethylene glycol to terminate the oxidation, filtering to obtain a precipitate, washing the precipitate with water until neutral, and performing suction filtration; the obtained precipitate is the 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 oxidizing agent 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 an oxidized bacterial cellulose solution with doxorubicin, adding cationic guar gum thereto, and mixing uniformly to crosslink sufficiently.

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

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

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

9. Use of the pH-sensitive composite hydrogel based on oxidized bacterial cellulose / cationic guar gum according to any one of claims 1-4 in the preparation of an antitumor drug.

Images