A modified chitosan carrier and preparation and application and curcumin-loaded modified chitosan nanoparticles

Abstract

This invention belongs to the field of curcumin-loaded carrier technology, and discloses a modified chitosan carrier, its preparation and application, and modified chitosan nanoparticles loaded with curcumin. Preparation method: Under magnetic stirring in an ice-water bath, a modifier is added dropwise to a chitosan solution, and the reaction is carried out at room temperature with stirring to obtain a product liquid. This product liquid is mixed with glacial acetic acid, dialyzed, and filtered to obtain a clear and transparent solution. When the modifier is an aqueous solution of trimethylammonium chloride, the clear and transparent solution is concentrated by rotary evaporation and freeze-dried to obtain the modified chitosan carrier. When the modifier is an aqueous solution of acrylamide, the clear and transparent solution is concentrated by rotary evaporation and hydrolyzed to obtain a hydrolysate, which is mixed with glacial acetic acid, dialyzed, and freeze-dried to obtain the modified chitosan carrier. This invention significantly improves the encapsulation efficiency, drug loading, and delivery stability of curcumin in the modified chitosan nanoparticle carrier prepared by this invention.

Description

Technical Field

[0001] This invention belongs to the field of curcumin-loaded carrier technology, and more specifically, relates to a modified chitosan carrier, its preparation and application, and modified chitosan nanoparticles loaded with curcumin. Background Technology

[0002] Curcumin, a diketone compound extracted from ginger plants, possesses various biological activities such as anti-tumor, anti-inflammatory, and antioxidant effects. However, its poor water solubility, low photothermal stability, and low gastrointestinal absorption efficiency severely limit its application in the food and pharmaceutical fields. Currently, the key to improving the application value of curcumin lies in solving its water solubility and bioavailability issues, and nanocarrier technology provides an effective approach to addressing these problems. Chitosan, as a natural cationic polysaccharide, has good biocompatibility, biodegradability, and mucosal adhesion, and is often used as a drug carrier. However, existing research on curcumin-loaded chitosan nanoparticles mostly focuses on optimizing preparation methods and exploring preliminary drug loading performance. Moreover, existing chitosan nanoparticles mainly rely on electrostatic adsorption to load drugs, resulting in generally low encapsulation efficiency and drug loading capacity for hydrophobic molecules like curcumin (usually below 50%). Furthermore, uneven particle size distribution, easy aggregation and precipitation during storage, and poor sustained-release performance lead to unstable curcumin delivery and severe burst release.

[0003] Currently, there is a lack of in-depth research on modifying chitosan to improve curcumin loading efficiency, stability, and sustained-release properties. Therefore, there is an urgent need to propose a new modified chitosan carrier, its preparation method, and its application for loading curcumin. Summary of the Invention

[0004] The purpose of this invention is to address the shortcomings of existing technologies by proposing a modified chitosan carrier and the preparation, application, and loading of curcumin-modified chitosan nanoparticles. Through a systematically optimized chemical modification strategy, this invention significantly improves the encapsulation efficiency, drug loading, and delivery stability of curcumin in the modified chitosan nanoparticle carrier prepared according to this invention.

[0005] To achieve the above objectives, the first aspect of the present invention provides a method for preparing a modified chitosan carrier, wherein the modifier used in the preparation method is an aqueous solution of trimethylammonium chloride or an aqueous solution of acrylamide, and includes the following steps: S1: Under magnetic stirring in an ice-water bath, the modifier is added dropwise to the chitosan solution, and then reacted at room temperature with stirring to obtain a product solution; the product solution is mixed with glacial acetic acid, and after dialysis and filtration, a clear and transparent solution is obtained; S2: When the modifier is an aqueous solution of trimethylammonium chloride, the clear and transparent solution is concentrated by rotary evaporation and freeze-dried to obtain a modified chitosan carrier (white sponge-like). When the modifier is an aqueous solution of acrylamide, the clear and transparent solution is concentrated by rotary evaporation and hydrolyzed to obtain a hydrolysate. The hydrolysate is mixed with glacial acetic acid, dialyzed, and freeze-dried to obtain a modified chitosan carrier (white sponge-like).

[0006] According to the present invention, preferably, the method for preparing the chitosan solution includes: mixing and stirring chitosan with LiOH-KOH-urea aqueous solution (preferably, stirring time is 1-10 min), freezing (preferably, freezing in a -80°C freezer for 0.5-8 h) to obtain slush, dispersing and stirring the slush, and then performing a freezing (preferably, freezing in a -80°C freezer for 2-12 h)-thawing (preferably thawing at room temperature with stirring) process at least once (preferably 1-3 times), and centrifuging (to remove air bubbles and a small amount of insoluble matter) to obtain the chitosan solution.

[0007] According to the present invention, preferably, the mass ratio of chitosan to LiOH-KOH-urea aqueous solution is (1-10):100.

[0008] According to the present invention, preferably, in the LiOH-KOH-urea aqueous solution, the concentration of LiOH is 7-9 wt%, the concentration of KOH is 6-8 wt%, and the concentration of urea is 7-9 wt%.

[0009] According to the present invention, preferably, the chitosan concentration in the chitosan solution is 1-10 wt%.

[0010] According to the present invention, preferably, the molar ratio of chitosan glucose units to the modifier is 1:(1-5).

[0011] According to the present invention, preferably, in step S1: The dripping time is 0.5-2 hours; The room temperature is 20-25℃ (the room temperature in this invention refers to 20-25℃); the reaction time is 2-24 hours. When the modifier is an aqueous solution of trimethylammonium chloride, the product solution is mixed with glacial acetic acid until the pH of the resulting mixture is 5-6.5; When the modifier is an aqueous solution of acrylamide, the product solution is mixed with glacial acetic acid until the pH of the resulting mixture is 7-8.

[0012] In this invention, as a preferred embodiment, the modifier is added dropwise to the chitosan solution over 0.5-2 hours. During the addition, the glass cake containing the chitosan solution is placed in an ice-water bath, and magnetic stirring is turned on. After the addition is completed, the ice-water bath is removed, allowing the modifier and chitosan solution to react at room temperature (20-25°C) under stirring conditions for 2-24 hours to obtain the product liquid.

[0013] According to the present invention, preferably, in step S2: The hydrolysis agent used is a 1-8 mol / L sodium hydroxide aqueous solution, with a dosage of 150 mL, a hydrolysis time of 12 h, and a hydrolysis temperature of room temperature; The hydrolysate was mixed with glacial acetic acid until the pH of the resulting mixture was 7.5-9.

[0014] In this invention, the dialysis bag used for dialysis has a molecular weight cutoff of MWCO 3500 and is placed in water for dialysis for 5 days.

[0015] The second aspect of the present invention provides a modified chitosan carrier prepared by the aforementioned modified chitosan carrier preparation method.

[0016] The third aspect of this invention provides the application of the modified chitosan carrier loaded with curcumin.

[0017] The fourth aspect of the present invention provides a modified chitosan nanoparticle loaded with curcumin. The modified chitosan nanoparticle loaded with curcumin is prepared by mixing and stirring a modified chitosan carrier with water under light-protected conditions to obtain a modified chitosan solution. An anhydrous ethanol solution of curcumin and an aqueous solution of sodium tripolyphosphate are mixed and added dropwise to the modified chitosan solution, followed by stirring, reaction, centrifugation and washing. The modified chitosan carrier is the modified chitosan carrier described above.

[0018] According to the present invention, preferably, when preparing the modified chitosan nanoparticles loaded with curcumin, the mass ratio of the modified chitosan carrier, sodium tripolyphosphate and curcumin is (50-500):(9-450):10.

[0019] In this invention, as a preferred embodiment, the method for preparing the curcumin-loaded modified chitosan nanoparticles includes: Weigh 50-500 mg (preferably 100 mg) of the modified chitosan carrier and dissolve it in 200 mL of deionized water. Place the solution on a magnetic stirrer and stir at 500 r / min for 2 h to ensure complete dissolution and obtain the modified chitosan solution. Prepare 90 mL of a sodium tripolyphosphate (TPP) aqueous solution at a concentration of 0.1-5 mg / mL (preferably 0.4 mg / mL); Weigh 10 mg of curcumin and dissolve it in 10 mL of anhydrous ethanol under light-protected conditions to obtain an anhydrous ethanol solution of curcumin. After thoroughly mixing anhydrous ethanol solution of curcumin and aqueous solution of sodium tripolyphosphate (TPP), the mixture was added dropwise to the modified chitosan solution over a period of 0.5-2 hours, preferably 1 hour. After the addition was complete, the mixture was stirred at room temperature for 2-10 hours (preferably 2 hours) to allow for a complete reaction. After the reaction was completed, the mixture was centrifuged at 10,000 r / min for 20 minutes and washed three times to obtain modified chitosan nanoparticles loaded with curcumin. The nanoparticles were stored at 4°C and protected from light during the above process.

[0020] According to the present invention, preferably, the modified chitosan nanoparticles loaded with curcumin have a particle size of 200-300 nm, a potential of 9-13 mV, a polydispersity index of 0.7-1.0, an encapsulation efficiency of 85-95%, and a drug loading of 8-8.5%.

[0021] The beneficial effects of the technical solution of the present invention are as follows: This invention significantly improves the encapsulation efficiency, drug loading, and delivery stability of curcumin by the modified chitosan nanoparticle carrier prepared by this invention through a systematically optimized chemical modification strategy, providing diversified and precisely selectable industrial technology solutions for the efficient delivery of curcumin.

[0022] Existing curcumin carriers often serve only as "containers," failing to fully utilize the bioactivity of both the carrier material itself and curcumin. The modified chitosan carrier prepared in this invention possesses excellent biocompatibility and positive charge. When loaded with curcumin, the two exhibit a synergistic inhibitory effect on pathogenic bacteria such as *Escherichia coli* (i.e., chitosan has a certain inhibitory effect on pathogenic bacteria, relying on electrostatic adsorption and membrane disruption; curcumin can effectively disrupt bacterial cell membranes and cell walls, inhibiting biofilm formation. The two form a physical carrier + active molecule delivery system, achieving a synergistic effect), thus enhancing functionality to a "1+1>2" effect. This expands the application of curcumin-loaded modified chitosan nanoparticles in antibacterial materials and food preservation.

[0023] This invention also systematically studies the effects of different modifier feeding ratios on the structure and drug loading performance of the product (the modified chitosan carrier prepared by this invention), clarifying the quantitative relationship between the degree of modification and drug loading performance, and providing clear and repeatable technical parameters for constructing an efficient drug loading system.

[0024] This invention introduces functional groups into the chitosan molecule through chemical modification, improving its physicochemical properties: quaternization modification (trimethylammonium chloride, introducing quaternary ammonium salt groups into the chitosan molecule) enhances the positive charge and water solubility of chitosan, strengthens its interaction with negatively charged substances, and is beneficial for targeted release and antibacterial activity; carboxyethylation modification (acrylamide) improves the water solubility and pH responsiveness of chitosan, facilitating targeted release into the intestine. This invention uses an ionogel method to prepare nanoparticles, employing sodium tripolyphosphate (TPP) as a crosslinking agent. Nanoparticles are formed through the electrostatic interaction between modified chitosan and TPP. This method eliminates the need for toxic crosslinking agents and exhibits high biocompatibility.

[0025] Other features and advantages of the present invention will be described in detail in the following detailed description section. Attached Figure Description

[0026] The above and other objects, features and advantages of the present invention will become more apparent from the more detailed description of exemplary embodiments of the invention in conjunction with the accompanying drawings.

[0027] Figure 1 Transmission electron microscopy (TEM) images of the modified chitosan carrier (QAC-3) and the modified chitosan nanoparticles loaded with curcumin (QAC-3C) prepared in Example 4 of this invention are shown.

[0028] Figure 2 Transmission electron microscopy (TEM) images of the modified chitosan carrier (CEC-2) and the modified chitosan nanoparticles loaded with curcumin (CEC-2C) prepared in Example 7 of this invention are shown.

[0029] Figure 3 Scanning electron microscope images of modified chitosan carrier (QAC-3), modified chitosan nanoparticles loaded with curcumin (QAC-3C), modified chitosan carrier (CEC-2), and modified chitosan nanoparticles loaded with curcumin (CEC-2C) after co-culturing with Escherichia coli are shown. Detailed Implementation

[0030] Preferred embodiments of the invention will now be described in more detail. While preferred embodiments of the invention are described below, it should be understood that the invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that the invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0031] Example 1

[0032] This embodiment provides a method for preparing a modified chitosan carrier. The modifier used in the preparation method is an aqueous solution of trimethylammonium chloride, and the method includes the following steps: (1) Preparation of chitosan solution Chitosan (2.0 g) was rapidly dispersed in 100 g of an 8 wt% LiOH-7 wt% KOH-8 wt% urea aqueous solution and stirred for 5 min. Then, it was placed in a -80℃ freezer and frozen for 0.5 h to obtain slush. The slush was dispersed and stirred, and then the freezing (freezing in a -80℃ freezer for 12 h) and thawing (thawing at room temperature with stirring) cycle was repeated twice. After centrifugation (to remove air bubbles and a small amount of insoluble matter), a clear and transparent chitosan solution (with a chitosan concentration of 2 wt%) was obtained.

[0033] (2) The modifier is added dropwise to 100g of the chitosan solution obtained in step (1) over 0.5h. During the addition, the glass cake (500mL) containing the chitosan solution is placed in an ice-water bath, and magnetic stirring is turned on. The molar ratio of chitosan glucose units to modifier is 1:1. After the addition is completed, the ice-water bath is removed, and the modifier and chitosan solution are reacted at room temperature (20-25℃) and under stirring conditions for 12h to obtain the product solution. The product solution is mixed with glacial acetic acid until the pH of the resulting mixture is 5.5. Then it is placed in a dialysis bag with a molecular weight cutoff of MWCO 3500, dialyzed in water for 5 days, filtered, and a clear and transparent solution is obtained.

[0034] (3) The clear and transparent solution was concentrated by rotary evaporation and freeze-dried to obtain a white sponge-like modified chitosan carrier (QAC-1).

[0035] This embodiment also utilizes the modified chitosan carrier obtained in this embodiment to load curcumin, thereby obtaining a modified chitosan nanoparticle (QAC-1C) loaded with curcumin. The method includes: Weigh 100 mg of the modified chitosan carrier obtained in this example and dissolve it in 200 mL of deionized water. Place it on a magnetic stirrer and stir at 500 r / min for 2 h to fully dissolve it, thus obtaining a modified chitosan solution. Prepare 90 mL of a 0.4 mg / mL sodium tripolyphosphate (TPP) aqueous solution; Weigh 10 mg of curcumin and dissolve it in 10 mL of anhydrous ethanol under light-protected conditions to obtain an anhydrous ethanol solution of curcumin. Anhydrous ethanol solution of curcumin and aqueous solution of sodium tripolyphosphate (TPP) were thoroughly mixed and then added dropwise to modified chitosan solution over 2 hours. After the addition was complete, the mixture was stirred at room temperature for 2 hours to allow for a complete reaction. After the reaction was completed, the mixture was centrifuged at 10,000 r / min for 20 min and washed 3 times to obtain modified chitosan nanoparticles loaded with curcumin. The nanoparticles were stored at 4°C and protected from light during the above process.

[0036] Example 2

[0037] This embodiment provides a method for preparing a modified chitosan carrier, wherein the modifier used in the preparation method is an aqueous solution of acrylamide, and includes the following steps: (1) The preparation of chitosan solution is the same as in Example 1.

[0038] (2) Using an aqueous solution of acrylamide, the same as in Example 1, a product solution was obtained; the product solution was mixed with glacial acetic acid until the pH of the resulting mixture was 8, and then placed in a dialysis bag with a molecular weight cutoff of MWCO 3500, and dialyzed in water for 5 days. After filtration, a clear and transparent solution was obtained.

[0039] (3) The clear and transparent solution was concentrated by rotary evaporation to obtain acrylamide-modified cellulose; the acrylamide-modified cellulose was mixed with 150 mL of 4 mol / L sodium hydroxide aqueous solution at room temperature and under stirring conditions, and hydrolyzed for 12 h to obtain hydrolysate; the hydrolysate was mixed with glacial acetic acid until the pH of the resulting mixture was 8, and then placed in a dialysis bag with a molecular weight cutoff of MWCO3500, and dialyzed in water for 5 days, and then freeze-dried to obtain modified chitosan carrier (CEC-1).

[0040] In this embodiment, the modified chitosan carrier obtained in this embodiment is used to load curcumin to obtain a modified chitosan nanoparticle loaded with curcumin (CEC-1C), and the method is the same as in Example 1.

[0041] To address the shortcomings of existing technologies where research on different modification strategies is fragmented and lacks horizontal comparison, this invention, for the first time, constructs a unified and systematic research platform. Using the same raw material activation technology, drug loading process, and evaluation standards, it conducts parallel studies on two strategies: quaternization modification and carboxyethylation modification. This scientifically reveals for the first time the differentiated performance advantages of these two modification strategies, providing a quantifiable, comparable, and selectable scientific basis for the efficient delivery of curcumin. To address the shortcomings of existing modification methods, which are often arbitrary and lack quantitative standards, this invention establishes a quantitative relationship between the degree of modification and drug loading performance through systematic molar ratio gradient experiments (QAC: 1:1-1:5; CEC: 1:1-1:5), thereby screening out the optimal "golden ratio" and making the technical solution reproducible and deterministic. To address the low loading efficiency of traditional chitosan nanoparticles for curcumin, this invention achieves a significant improvement in encapsulation efficiency through systematically optimized chemical modification, realizing a qualitative leap in drug loading performance.

[0042] Examples 3-6

[0043] The only difference between Example 3 and Example 1 is that the molar ratio of chitosan glucose units to modifier is 1:2, resulting in the corresponding modified chitosan carrier (QAC-2) and modified chitosan nanoparticles loaded with curcumin (QAC-2C).

[0044] The only difference between Example 4 and Example 1 is that the molar ratio of chitosan glucose units to modifier is 1:3, resulting in the corresponding modified chitosan carrier (QAC-3) and modified chitosan nanoparticles loaded with curcumin (QAC-3C).

[0045] The only difference between Example 5 and Example 1 is that the molar ratio of chitosan glucose units to modifier is 1:4, resulting in the corresponding modified chitosan carrier (QAC-4) and modified chitosan nanoparticles loaded with curcumin (QAC-4C).

[0046] The only difference between Example 6 and Example 1 is that the molar ratio of chitosan glucose units to modifier is 1:5, resulting in the corresponding modified chitosan carrier (QAC-5) and modified chitosan nanoparticles loaded with curcumin (QAC-5C).

[0047] Examples 7-10

[0048] The only difference between Example 7 and Example 2 is that the molar ratio of chitosan glucose units to modifier is 1:2, resulting in the corresponding modified chitosan carrier (CEC-2) and modified chitosan nanoparticles loaded with curcumin (CEC-2C).

[0049] The only difference between Example 8 and Example 2 is that the molar ratio of chitosan glucose units to modifier is 1:3, resulting in the corresponding modified chitosan carrier (CEC-3) and modified chitosan nanoparticles loaded with curcumin (CEC-3C).

[0050] The only difference between Example 9 and Example 2 is that the molar ratio of chitosan glucose units to modifier is 1:4, resulting in the corresponding modified chitosan carrier (CEC-4) and modified chitosan nanoparticles loaded with curcumin (CEC-4C).

[0051] The only difference between Example 10 and Example 2 is that the molar ratio of chitosan glucose units to modifier is 1:5, resulting in the corresponding modified chitosan carrier (CEC-5) and modified chitosan nanoparticles loaded with curcumin (CEC-5C).

[0052] Test case

[0053] This test example evaluates the particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency, drug loading, microstructure, and antibacterial activity of the modified chitosan nanoparticles loaded with curcumin obtained in the above examples.

[0054] 1. Nanoparticle size and zeta potential analysis

[0055] Take 1 mL of sample and dilute it with 9 mL of deionized water. Then add the solution to be tested into the sample cell and insert it into the instrument to test the particle size, polydispersity index (PDI) and zeta potential.

[0056] 2. Microscopic morphology analysis of nanoparticles

[0057] After diluting the samples, they were dropped onto an ultrathin carbon support film, allowed to air dry, and then observed using a JEOL JEM 2010 FEF transmission electron microscope.

[0058] 3. Testing of drug loading and encapsulation efficiency of nanoparticles

[0059] First, a standard curve was established by measuring the UV absorbance of curcumin at 426 nm using a UV spectrophotometer. 10.0 mg of curcumin was accurately weighed and dissolved in a 10:1 mixture of acetonitrile and water to a final volume of 10 mL, preparing a 1 mg / mL curcumin stock solution. The stock solution was serially diluted to a predetermined concentration gradient, and the UV absorbance at 426 nm was measured for each concentration to establish the standard curve. A certain amount of the sample to be tested was weighed and its absorbance was measured under the same conditions as the standard curve determination. The curcumin content in the sample was then calculated using the standard curve. The encapsulation efficiency (the percentage of drug loaded in the nanoparticles relative to the initial total drug amount, reflecting the carrier's drug loading efficiency) and drug loading (the percentage of drug mass loaded in the nanoparticles relative to the total mass of the nanoparticles, reflecting the carrier's drug carrying capacity) can be calculated using formulas.

[0060] 4. Antibacterial effect evaluation

[0061] Adjust the E. coli concentration to 10 7 CFU / mL was added to modified chitosan carriers (CEC-2, QAC-3) and drug-loaded nanoparticles (CEC-2C, QAC-3C), and co-cultured with bacterial culture for 7 days. The cultured bacteria were collected, fixed with 2.5% glutaraldehyde, dehydrated by ethanol gradient, sputter-coated with gold, and the morphological changes of the bacteria were observed by scanning electron microscopy.

[0062] The test results are as follows.

[0063] Table 1

[0064] As shown in Table 1, both modification strategies exhibit an optimal molar ratio. Encapsulation efficiency increases with increasing quaternization degree, but particle size and PDI reach an optimal balance at QAC-3C. The encapsulation efficiency of carboxyethyl chitosan-loaded nanoparticles peaks at CEC-2C (92.1%). Under the QAC modification method, the nanoparticles exhibit strong positive charge, which is beneficial for targeting / antibacterial activity, and a more uniform particle size distribution. In contrast, CEC-modified nanoparticles show higher encapsulation efficiency / drug loading and smaller particle size. This demonstrates a clear quantitative relationship between the degree of modification and drug loading performance, and the existence of an optimal golden ratio, providing a scientific basis for the reproducibility of the technical solution.

[0065] like Figure 1 and 2 As shown, this invention obtains key information such as morphology, structure, size, and dispersibility at the nanoscale using transmission electron microscopy. Specifically: Transmission electron microscopy images of QAC-3 and curcumin-loaded nanoparticles QAC-3C ( Figure 1 In the blank nanoparticles, all were spherical nanoparticles with relatively uneven size (around 246.8 nm), while the size of QAC-3C was slightly increased (around 260.9 nm). Transmission electron microscopy images of CEC-2 and curcumin-loaded nanoparticles CEC-2C ( Figure 2 In the blank nanoparticles, all are relatively uniform in size (around 207 nm) and are spherical nanoparticles, while the size of CEC-2C is slightly increased (around 224.2 nm).

[0066] like Figure 3 As shown, this invention aims to evaluate the antibacterial activity of carriers (CEC-2, QAC-3) and their drug delivery systems (CEC-2C, QAC-3C) against *Escherichia coli* using scanning electron microscopy (SEM), exploring their antibacterial effect and possible mechanism of action. SEM observation revealed that the bacterial membranes treated with unloaded carriers exhibited rough wrinkles but maintained a normal morphology; the bacteria in the drug-loaded group lost their original shape and were difficult to identify. This indicates that curcumin has a strong bactericidal effect against *Escherichia coli*, especially the QAC-3C-treated group. This may be due to the interaction between cationic nanoparticles and the negatively charged bacterial membrane, disrupting the cell membrane and thus exhibiting a stronger antibacterial effect.

[0067] The various embodiments of the present invention have been described above. These descriptions are exemplary and not exhaustive, nor are they limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments.

Claims

1. A method for preparing a modified chitosan carrier, characterized in that, The preparation method uses trimethylammonium chloride aqueous solution or acrylamide aqueous solution as the modifier, and includes the following steps: S1: Under magnetic stirring in an ice-water bath, the modifier is added dropwise to the chitosan solution, and then reacted at room temperature with stirring to obtain a product solution; the product solution is mixed with glacial acetic acid, and after dialysis and filtration, a clear and transparent solution is obtained; S2： When the modifier is an aqueous solution of trimethylammonium chloride, the clear and transparent solution is concentrated by rotary evaporation and freeze-dried to obtain a modified chitosan carrier; When the modifier is an aqueous solution of acrylamide, the clear and transparent solution is concentrated by rotary evaporation and hydrolyzed to obtain a hydrolysate. The hydrolysate is mixed with glacial acetic acid, dialyzed, and freeze-dried to obtain a modified chitosan carrier.

2. The method for preparing the modified chitosan carrier according to claim 1, wherein, The method for preparing the chitosan solution includes: mixing and stirring chitosan with LiOH-KOH-urea aqueous solution, freezing to obtain slush, dispersing and stirring the slush, then performing a freeze-thaw process at least once, and centrifuging to obtain the chitosan solution.

3. The method for preparing the modified chitosan carrier according to claim 2, wherein, The mass ratio of chitosan to LiOH-KOH-urea aqueous solution is (1-10):100; In the LiOH-KOH-urea aqueous solution, the concentration of LiOH is 7-9 wt%, the concentration of KOH is 6-8 wt%, and the concentration of urea is 7-9 wt%. The chitosan concentration in the chitosan solution is 1-10 wt%.

4. The method for preparing the modified chitosan carrier according to claim 1, wherein, The molar ratio of chitosan glucose units to the modifier is 1:(1-5).

5. The method for preparing the modified chitosan carrier according to claim 1, wherein, In step S1: The dripping time is 0.5-2 hours; The room temperature is 20-25℃; the reaction time is 2-24 hours. When the modifier is an aqueous solution of trimethylammonium chloride, the product solution is mixed with glacial acetic acid until the pH of the resulting mixture is 5-6.5; When the modifier is an aqueous solution of acrylamide, the product solution is mixed with glacial acetic acid until the pH of the resulting mixture is 7-8; In step S2: The hydrolyzing agent used is a 1-8 mol / L sodium hydroxide aqueous solution; The hydrolysate was mixed with glacial acetic acid until the pH of the resulting mixture was 7.5-9.

6. The modified chitosan carrier prepared by the method for preparing the modified chitosan carrier according to any one of claims 1-5.

7. The application of curcumin loaded on the modified chitosan carrier as described in claim 6.

8. A modified chitosan nanoparticle loaded with curcumin, characterized in that, The modified chitosan nanoparticles loaded with curcumin were prepared by mixing and stirring the modified chitosan carrier with water under light-protected conditions to obtain a modified chitosan solution. An anhydrous ethanol solution of curcumin and an aqueous solution of sodium tripolyphosphate were mixed and added dropwise to the modified chitosan solution. The mixture was then stirred, reacted, centrifuged, and washed to obtain the final product. The modified chitosan carrier is the modified chitosan carrier according to claim 6.

9. The modified chitosan nanoparticles loaded with curcumin according to claim 8, wherein, When preparing the modified chitosan nanoparticles loaded with curcumin, the mass ratio of the modified chitosan carrier, sodium tripolyphosphate, and curcumin is (50-500):(9-450):

10.

10. The modified chitosan nanoparticles loaded with curcumin according to claim 8, wherein, The modified chitosan nanoparticles loaded with curcumin have a particle size of 200-300 nm, a potential of 9-13 mV, a polydispersity index of 0.7-1.0, an encapsulation efficiency of 85-95%, and a drug loading of 8-8.5%.

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