A modified chitosan / layered double hydroxide composite material, a preparation method and application thereof
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-20
- Publication Date
- 2026-08-11
AI Technical Summary
然而，这些方法或是仅从单一维度改善壳聚糖的性能，或是对药物释放行为的调控效果有限，仍难以从根本上解决壳聚糖基载体药物释放可控性不足的问题
（1）结构与性能协同增强
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Figure CN122537541A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical materials technology, specifically to a modified chitosan / layered double metal hydroxide composite material and its preparation method, as well as the application of this composite material in drug delivery carriers. Background Technology
[0002] Chitosan is a natural cationic polysaccharide obtained from chitin through deacetylation. It possesses excellent biocompatibility, biodegradability, and low immunogenicity, attracting widespread attention in biomedical fields such as drug delivery systems, tissue engineering, and wound repair. The chitosan molecular chain contains abundant amino and hydroxyl functional groups, readily enabling the construction of three-dimensional network structures through chemical cross-linking or physical interactions to form hydrogel materials, thereby facilitating drug loading and delivery.
[0003] However, single chitosan-based materials still face several key technical bottlenecks in practical drug delivery applications. First, chitosan itself has poor solubility in neutral or alkaline aqueous solutions, limiting the uniform loading and effective release of drugs. Second, chitosan-based hydrogels generally have low mechanical strength, making them prone to structural collapse or premature degradation in physiological environments, leading to burst release of drugs and making it difficult to achieve long-term sustained release. In addition, the encapsulation efficiency of pure chitosan-based materials is limited, resulting in insufficient drug utilization and restricting their clinical application prospects as efficient drug carriers.
[0004] To address these shortcomings, researchers have explored various modification strategies. For instance, introducing hydrophilic groups such as carboxymethyl groups into the chitosan molecular structure disrupts the strong hydrogen bonds between molecules, thus improving its solubility and processability to some extent. Another example is the physical blending of chitosan with inorganic materials such as cellulose nanocrystals and hydroxyapatite, which produces composite hydrogels with improved mechanical strength and thermal stability. However, these methods either only improve chitosan's properties from a single dimension or have limited effects on regulating drug release behavior, failing to fundamentally solve the problem of insufficient controllability of drug release from chitosan-based carriers. Therefore, developing a novel chitosan-based composite material with both good mechanical properties and controllable drug release capability has become a key research focus and urgent need in this field.
[0005] Layered double hydroxides (LDHs) are a class of two-dimensional layered inorganic materials with a hydrotalcite-like structure. Among various LDH materials, zinc-aluminum layered double hydroxides (ZnAl-LDH) have attracted much attention due to their good biocompatibility and excellent anion exchange performance. Based on this, this invention aims to provide a composite material in which ZnAl-LDH is introduced into a modified chitosan matrix. Through the interfacial synergistic effect and interlayer ion exchange mechanism between the two materials, drug release behavior can be regulated to achieve long-acting sustained release and high drug utilization, providing a superior carrier material for drug release. Summary of the Invention
[0006] The technical problem to be solved by the present invention is to provide a modified chitosan / layered double metal hydroxide composite material and its preparation method, as well as the application of the composite material in drug release carriers, in order to address the shortcomings of the prior art.
[0007] Preferably, the composite material comprises a carboxymethyl chitosan-grafted polyacrylic acid polymer and an oleate-modified zinc-aluminum layered bimetallic hydroxide.
[0008] Preferably, the oleate-modified zinc-aluminum layered bimetallic hydroxide is dispersed in an intercalated form in a carboxymethyl chitosan-grafted polyacrylic acid polymer.
[0009] More preferably, the oleate-modified zinc-aluminum layered bimetallic hydroxide is a potassium oleate-modified zinc-aluminum layered bimetallic hydroxide.
[0010] In this invention, the hydroxyl groups on the surface of the oleate-modified zinc-aluminum layered bimetallic hydroxide form a hydrogen bond network with the carboxyl and amino groups on the surface of the carboxymethyl chitosan grafted with polyacrylic acid. The two are composited together in situ. Some polymer chain segments are intercalated between the layers of the oleate-modified zinc-aluminum layered bimetallic hydroxide to form an intercalated nanocomposite structure. This structure has high thermal stability and can effectively improve the drug release ability.
[0011] This invention also proposes a method for preparing a modified chitosan / layered double metal hydroxide composite material, the preparation method comprising: Oleate-modified zinc-aluminum layered bimetallic hydroxide and carboxymethyl chitosan were dispersed in an aqueous solution, and then acrylic acid neutralizing solution was added. Under the action of an initiator and a crosslinking agent, an in-situ polymerization reaction was carried out to obtain the composite material.
[0012] In this invention, the acrylic acid neutralization solution is an acrylic acid solution neutralized to pH=7 with alkali.
[0013] Preferably, the preparation method of the oleate-modified zinc-aluminum layered bimetallic hydroxide includes: dissolving potassium oleate, sodium carbonate and sodium hydroxide in deionized water, adding AlCl3·6H2O and ZnCl2 in sequence, stirring continuously to react, cooling to room temperature, filtering to obtain the precipitated solid, washing with deionized water 3-5 times, and finally vacuum drying to obtain the oleate-modified zinc-aluminum layered bimetallic hydroxide.
[0014] Preferably, the molar ratio of potassium oleate, sodium carbonate and sodium hydroxide is 1:5:60; the molar ratio of potassium oleate:AlCl3·6H2O:ZnCl2 is 1:10:20.
[0015] Preferably, the stirring reaction temperature is 60-90℃ and the stirring reaction time is 1-3h.
[0016] Preferably, the in-situ polymerization reaction is carried out under an inert atmosphere, the reaction temperature is 50-80℃, and the reaction time is 10-20h.
[0017] Preferably, the mass ratio of carboxymethyl chitosan to acrylic acid is 1:2-10.
[0018] Preferably, the mass ratio of the oleate-modified zinc-aluminum layered bimetallic hydroxide to carboxymethyl chitosan is 1:10-50.
[0019] The present invention also proposes the application of the above-mentioned composite material or the composite material obtained by the above-mentioned preparation method in drug release.
[0020] Beneficial effects of this invention: (1) Synergistic enhancement of structure and performance Modified ZnAl-LDH was uniformly embedded into a three-dimensional network of carboxymethyl chitosan grafted with polyacrylic acid via an in-situ composite method, achieving molecular-scale composite of organic and inorganic components. The LDH sheets, acting as physical cross-linking points, significantly enhanced the material's mechanical strength and thermal stability, overcoming the shortcomings of poor mechanical properties and excessive swelling inherent in single organic hydrogels. Simultaneously, the organic polymer network endowed the material with excellent flexibility and plasticity, solving the problems of high brittleness and inability to self-support molding in purely inorganic LDH materials. The resulting composite material possesses both strength and toughness, achieving a synergistic improvement in overall performance. (2) The drug controlled release capability is significantly optimized. The composite material constructs a dual drug storage and transport system of "polymer network physical encapsulation" and "LDH interlayer ion intercalation", which improves the drug loading capacity and realizes stable and long-lasting gradient sustained release of diclofenac sodium. The composite material has both pH response (polymer carboxyl ionization) and ionic strength response (LDH interlayer competitive replacement) dual release mechanisms, which can autonomously adjust the drug release rate according to different physiological microenvironments to achieve precise release. (3) Excellent biocompatibility and degradation safety The main component, carboxymethyl chitosan, is derived from natural polysaccharides and possesses excellent biocompatibility, degradability, and inherent mucosal adhesion, which helps prolong the in vivo retention time and improve drug bioavailability. LDH exhibits low biotoxicity at a controllable nanoscale, and its lamellar metal ions are slowly dissolved as the polymer network gradually degrades, avoiding biotoxicity caused by sudden increases in local metal ion concentration. The final degradation products are safe and non-toxic, and can be absorbed or metabolized and excreted in vivo. (4) The preparation process is simple and the product structure is stable. The one-pot in-situ polymerization process is simple, has mild conditions, is easy to operate, and is suitable for large-scale production.
[0021] In summary, this patent provides a novel composite material for drug delivery carriers that has good biocompatibility, stable mechanical properties, and long-lasting release, and the process for this composite material is simple. Attached Figure Description
[0022] Figure 1 Infrared spectra of Example 1, Comparative Example 1, and modified ZnAl-LDH; Figure 2 X-ray diffraction patterns of Example 1, Comparative Example 1, and modified ZnAl-LDH; Figure 3 The images shown are scanning electron microscope (SEM) images of Example 1 and Comparative Example 1, wherein... Figure 3 (a) is a scanning electron microscope image of the hydrogel in Comparative Example 1. Figure 3 (b) is a scanning electron microscope image of the composite material in Example 1; Figure 4 This is a transmission electron microscope image of Example 1; Figure 5 The figures are thermal analysis curves for Example 1 and Comparative Example 1, where... Figure 5 (a) TG plots of Example 1 and Comparative Example 1; Figure 5 (b) DTG diagrams of Example 1 and Comparative Example 1; Figure 6 The figures show the mechanical property test results for Examples 1, 2, and 1, where... Figure 6 (a) is the stress-strain curve. Figure 6 (b) represents Young's modulus and tensile strength; Figure 7 Example 1: Particle size distribution before and after loading LDH / OCMCS-g-PAA, where... Figure 7 (a) is the particle size distribution diagram of LDH / OCMCS-g-PAA in Example 1. Figure 7 (b) is the particle size distribution diagram of DCF / LDH / OCMCS-g-PAA; Figure 8 The figures show the drug release curves for Example 1, Comparative Example 1, and modified ZnAl-LDH. Detailed Implementation
[0023] To facilitate understanding of the present invention, a more comprehensive description will be given below with reference to specific embodiments. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a more thorough and complete understanding of the disclosure of the present invention.
[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.
[0025] The technical solution of the present invention will now be described more clearly and completely with reference to specific embodiments and comparative examples.
[0026] In this invention, the synthesis steps of each embodiment and the subsequent performance comparison require the use of modified ZnAl-LDH. In order to control variables, a batch of modified ZnAl-LDH will be prepared for the series of experiments of this invention. Preparation process of modified ZnAl-LDH: Weigh out potassium oleate, sodium carbonate and sodium hydroxide in a molar ratio of 1:5:60, dissolve them in 250 mL of deionized water, stir well, and then add 100 mmol of AlCl3·6H2O and 200 mmol of ZnCl2 in sequence. After stirring at 80 °C for 2 h, cool to room temperature and filter. Wash the filter residue with deionized water 3-5 times and then vacuum dry for 48 h. The obtained product is called modified ZnAl-LDH.
[0027] Example 1
[0028] This embodiment proposes a composite material, the preparation method of which includes the following steps: 5% (by mass) of modified ZnAl-LDH was placed in a flask, deionized water was added, and the mixture was stirred at room temperature for 24 hours under nitrogen protection to obtain a homogeneous solution. The solution with a concentration of 0.06... A g / mL carboxymethyl chitosan solution was added to a modified ZnAl-LDH solution and stirred at room temperature for 3 h. Then, acrylic acid solution (pH=7) was neutralized with 6 mol / L NaOH, where the mass ratio of carboxymethyl chitosan to acrylic acid was 1:6. After stirring at 60 °C for 10 min, 0.5 wt% potassium persulfate was added and stirred for 30 min. Then, 1.0 wt% N,N-methylenebisacrylamide was added and stirred until homogeneous to obtain a mixture. The mixture was centrifuged and placed in a nitrogen atmosphere at 60 °C for 16 h. After the reaction was complete, it was cooled to room temperature to obtain a monolithic hydrogel. The monolithic hydrogel was cut into small pieces and immersed in water for 3-5 days to remove soluble byproducts. These gel pieces were then transferred to a methanol solution for thorough dehydration. The samples were dried under vacuum to constant weight to obtain the ZnAl-LDH / OCMCS-g-PAA composite material. The drug loading of the composite material for DCF was measured to be 18.1%, and the encapsulation efficiency was 92.7%.
[0029] Example 2
[0030] This embodiment proposes a composite material, the preparation method of which includes the following steps: 8% (by mass) of modified ZnAl-LDH was placed in a flask, deionized water was added, and the mixture was stirred at room temperature for 24 hours under nitrogen protection to obtain a homogeneous solution. A 0.06 g / mL carboxymethyl chitosan solution was added to the modified ZnAl-LDH solution, and the mixture was stirred at room temperature for 3 hours. Then, a solution containing 6... Acrylic acid solution (pH=7) was neutralized with mol / L NaOH, wherein the mass ratio of carboxymethyl chitosan to acrylic acid was 1:6. After stirring at 60℃ for 10 minutes, 0.5wt% of potassium persulfate was added and stirred for 30 minutes. Then, 1.0wt% of N,N-methylenebisacrylamide was added and stirred until homogeneous to obtain a mixture. The mixture was centrifuged and placed in a nitrogen atmosphere and reacted at 60℃ for 16 hours. After the reaction was completed, it was cooled to room temperature to obtain a monolithic hydrogel. The monolithic hydrogel was cut into small pieces and immersed in water for 3-5 days to remove soluble byproducts. These gel pieces were then transferred to methanol solution for thorough dehydration. The samples were dried under vacuum to constant weight to obtain the composite material. The drug loading of the composite material for DCF was measured to be 18.6%, and the encapsulation efficiency was 93.1%.
[0031] Example 3
[0032] This embodiment proposes a composite material, the preparation method of which includes the following steps: 5% (by mass) of modified ZnAl-LDH was placed in a flask, deionized water was added, and the mixture was stirred at room temperature for 24 hours under nitrogen protection to obtain a homogeneous solution. A 0.06 g / mL carboxymethyl chitosan solution was added to the modified ZnAl-LDH solution, and the mixture was stirred at room temperature for 3 hours. Then, a solution containing 6... Acrylic acid solution (pH=7) was neutralized with mol / L NaOH, wherein the mass ratio of carboxymethyl chitosan to acrylic acid was 1:6. After stirring at 60℃ for 10 minutes, 0.3wt% of potassium persulfate was added and stirred for 30 minutes. Then, 1.0wt% of N,N-methylenebisacrylamide was added and stirred until homogeneous to obtain a mixture. The mixture was centrifuged and placed in a nitrogen atmosphere and reacted at 60℃ for 16 hours. After the reaction was completed, it was cooled to room temperature to obtain a monolithic hydrogel. The monolithic hydrogel was cut into small pieces and immersed in water for 3-5 days to remove soluble byproducts. These gel pieces were then transferred to methanol solution for thorough dehydration. The samples were dried under vacuum to constant weight to obtain the composite material. The drug loading of the composite material for DCF was measured to be 16.3%, and the encapsulation efficiency was 90.6%.
[0033] Example 4
[0034] This embodiment proposes a composite material, the preparation method of which includes the following steps: 5% (by mass) of modified ZnAl-LDH was placed in a flask, deionized water was added, and the mixture was stirred at room temperature for 24 hours under nitrogen protection to obtain a homogeneous solution. A 0.06 g / mL carboxymethyl chitosan solution was added to the modified ZnAl-LDH solution, and the mixture was stirred at room temperature for 3 hours. Then, a solution containing 6... Acrylic acid solution (pH=7) was neutralized with mol / L NaOH, wherein the mass ratio of carboxymethyl chitosan to acrylic acid was 1:6. After stirring at 60℃ for 10 minutes, 0.5wt% of potassium persulfate was added and stirred for 30 minutes. Then, 0.25wt% of N,N-methylenebisacrylamide was added and stirred until homogeneous to obtain a mixture. The mixture was centrifuged and placed in a nitrogen atmosphere and reacted at 60℃ for 16 hours. After the reaction was completed, it was cooled to room temperature to obtain a monolithic hydrogel. The monolithic hydrogel was cut into small pieces and immersed in water for 3-5 days to remove soluble byproducts. These gel pieces were then transferred to methanol solution for thorough dehydration. The samples were dried under vacuum to constant weight to obtain a composite material. The drug loading of the composite material for DCF was measured to be 16.5%, and the encapsulation efficiency was 92.1%.
[0035] Example 5
[0036] This embodiment proposes a composite material, the preparation method of which includes the following steps: 5% (by mass) of modified ZnAl-LDH was placed in a flask, deionized water was added, and the mixture was stirred at room temperature for 24 hours under nitrogen protection to obtain a homogeneous solution. A 0.06 g / mL carboxymethyl chitosan solution was added to the modified ZnAl-LDH solution, and the mixture was stirred at room temperature for 3 hours. Then, a solution containing 6... Acrylic acid solution (pH=7) was neutralized with mol / L NaOH, wherein the mass ratio of carboxymethyl chitosan to acrylic acid was 1:4. After stirring at 60℃ for 10 minutes, 0.5wt% of potassium persulfate was added and stirred for 30 minutes. Then, 1.0wt% of N,N-methylenebisacrylamide was added and stirred until homogeneous to obtain a mixture. The mixture was centrifuged and placed in a nitrogen atmosphere and reacted at 60℃ for 16 hours. After the reaction was completed, it was cooled to room temperature to obtain a monolithic hydrogel. The monolithic hydrogel was cut into small pieces and immersed in water for 3-5 days to remove soluble byproducts. These gel pieces were then transferred to methanol solution for thorough dehydration. The samples were dried under vacuum to constant weight to obtain the composite material. The drug loading of the composite material for DCF was measured to be 15.8%, and the encapsulation efficiency was 91.4%.
[0037] Example 6
[0038] This embodiment proposes a composite material, the preparation method of which includes the following steps: 5% (by mass) of modified ZnAl-LDH was placed in a flask, deionized water was added, and the mixture was stirred at room temperature for 24 hours under nitrogen protection to obtain a homogeneous solution. A 0.06 g / mL carboxymethyl chitosan solution was added to the modified ZnAl-LDH solution, and the mixture was stirred at room temperature for 3 hours. Then, a solution containing 6... Acrylic acid solution (pH=7) was neutralized with mol / L NaOH, wherein the mass ratio of carboxymethyl chitosan to acrylic acid was 1:6. After stirring at 60℃ for 10 minutes, 0.5wt% of potassium persulfate was added and stirred for 30 minutes. Then, 1.0wt% of N,N-methylenebisacrylamide was added and stirred until homogeneous to obtain a mixture. The mixture was centrifuged and placed in a nitrogen atmosphere and reacted at 40℃ for 16 hours. After the reaction was completed, it was cooled to room temperature to obtain a monolithic hydrogel. The monolithic hydrogel was cut into small pieces and immersed in water for 3-5 days to remove soluble byproducts. These gel pieces were then transferred to methanol solution for thorough dehydration. The samples were dried under vacuum to constant weight to obtain the composite material. The drug loading of the composite material for DCF was measured to be 15.3%, and the encapsulation efficiency was 90.6%.
[0039] Example 7
[0040] This embodiment proposes a composite material, the preparation method of which includes the following steps: 5% (by mass) of modified ZnAl-LDH was placed in a flask, deionized water was added, and the mixture was stirred at room temperature for 24 hours under nitrogen protection to obtain a homogeneous solution. A 0.06 g / mL carboxymethyl chitosan solution was added to the modified ZnAl-LDH solution, and the mixture was stirred at room temperature for 3 hours. Then, a solution containing 6... Acrylic acid solution (pH=7) was neutralized with mol / L NaOH, wherein the mass ratio of carboxymethyl chitosan to acrylic acid was 1:6. After stirring at 60℃ for 10 minutes, 0.5wt% of potassium persulfate was added and stirred for 30 minutes. Then, 1.0wt% of N,N-methylenebisacrylamide was added and stirred until homogeneous to obtain a mixture. The mixture was centrifuged and placed in a nitrogen atmosphere and reacted at 60℃ for 4 hours. After the reaction was completed, it was cooled to room temperature to obtain a monolithic hydrogel. The monolithic hydrogel was cut into small pieces and immersed in water for 3-5 days to remove soluble byproducts. These gel pieces were then transferred to methanol solution for thorough dehydration. The samples were dried under vacuum to constant weight to obtain the composite material. The drug loading of the composite material for DCF was measured to be 13.6%, and the encapsulation efficiency was 90.4%.
[0041] Comparative Example 1 This comparative example presents a hydrogel, the preparation method of which includes the following steps: First, carboxymethyl chitosan was dissolved in water to form a solution with a concentration of 0.06 g / mL. Acrylic acid (pH=7) neutralized with 6 mol / L NaOH was added, with a mass ratio of carboxymethyl chitosan to acrylic acid of 1:6. The mixture was stirred at 60℃ for 10 minutes. Then, 0.5 wt% of potassium persulfate was added and stirred for 30 minutes. Finally, 1.0 wt% of N,N-methylenebisacrylamide was added and stirred until homogeneous to obtain a mixture. The mixture was centrifuged and reacted at 60℃ for 16 hours under a nitrogen atmosphere. After the reaction was completed, the mixture was cooled to room temperature to form a hydrogel. The hydrogel was cut into small pieces and immersed in water for 3-5 days to remove soluble byproducts. The gel pieces were then transferred to a methanol solution for thorough dehydration. The sample was dried under vacuum to constant weight to obtain OCMCS-g-PAA. The drug loading of this material to DCF was measured to be 11.3%, and the encapsulation efficiency was 93.5%.
[0042] Characterization test Figure 1 The infrared spectra of Example 1, Comparative Example 1, and modified ZnAl-LDH are shown below. Figure 1 It can be seen that the 3400 to 3600 cm⁻¹ of the composite material ZnAl-LDH / OCMCS-g-PAA is... -1 The -OH stretching vibration peak in the region becomes broader and thicker, indicating that a hydrogen bond network is formed between the hydroxyl groups on the surface of the ZnAl-LDH laminate and the carboxyl and amino groups on the hydrogel backbone, at 1620 cm⁻¹. -1 The position of the peak reflects NH4+ Extensive vibration, at 1410cm -1 The peak belongs to The stretching vibration indicates that there is ionic cross-linking between amino and some carboxyl groups, that is, ZnAl-LDH was successfully complexed in OCMCS-g-PAA through the synergistic effect of hydrogen bonding and electrostatic attraction; Figure 2 The X-ray diffraction patterns of Example 1, Comparative Example 1, and modified ZnAl-LDH are shown below. Figure 2 It can be seen that the diffraction pattern of the modified ZnAl-LDH has multiple sharp peaks, indicating that it has a highly ordered structure. Furthermore, potassium oleate modification reduces the aggregation of ZnAl-LDH particles. The spectrum of ZnAl-LDH / OCMCS-g-PAA clearly shows that the composite material retains both the amorphous diffuse peaks of the polymer matrix and the characteristic diffraction peaks of the modified ZnAl-LDH, confirming that the layered structure of the modified ZnAl-LDH is effectively maintained in the hydrogel matrix. No new sharp diffraction peaks appear in the composite material spectrum, indicating that no new crystalline phase is generated during the composite process. The modified ZnAl-LDH and the polymer are mainly bonded through interaction. Observations show that the (003) diffraction peak of the modified ZnAl-LDH in the composite material is relatively smaller than that of the pure ZnAl-LDH. The angle moves to a lower direction, according to Bragg's equation. It can be known that The decrease in d and the increase in d indicate that during the composite process, some polymer chains were intercalated between the modified ZnAl-LDH layers, forming an intercalated nanocomposite structure. The XRD diffraction pattern results confirmed from the structural level that the modified ZnAl-LDH was dispersed in OCMCS-g-PAA hydrogel in an intercalated form. Figure 3 The images shown are scanning electron microscope (SEM) images of Example 1 and Comparative Example 1, wherein... Figure 3 (a) is a scanning electron microscope image of the hydrogel in Comparative Example 1. Figure 3(b) is a scanning electron microscope image of the composite material in Example 1. In image (a), it can be observed that OCMCS-g-PAA has a typical three-dimensional structure, exhibiting a layered stacked morphology with a large polymer structure on the surface, uneven pore distribution, relatively loose structure, and a large specific surface area. The relatively smooth pore walls indicate that there is good compatibility between OCMCS and PAA branches, forming a relatively uniform polymer matrix. In image (b), the microstructure of the composite material ZnAl-LDH / OCMCS-g-PAA has undergone significant changes. Significant changes were observed, exhibiting a denser and more uniform granular packing morphology. The pore wall surface was no longer smooth, showing a noticeable roughness. This was mainly because the modified ZnAl-LDH had been successfully distributed in the polymer matrix. This trend towards a denser structure confirmed that the modified ZnAl-LDH enhanced the crosslinking density of the network through the electrostatic attraction between its positively charged lamellars and the negatively charged polymer chains. SEM images confirmed from the microscopic morphology that the modified ZnAl-LDH had been successfully embedded in the OCMCS-g-PAA hydrogel network. Figure 4 The image shown is a transmission electron microscope (TEM) image of Example 1. The two-dimensional sheet-like structure is clearly visible in Figure a, which is a typical TEM morphology of ZnAl-LDH. This indicates that the composite process did not destroy the layered crystal structure of LDH. The lateral dimensions of the sheets are about 20-60 nm. The dark sheets in the image are ZnAl-LDH, and the light gray ones are OCMCS-g-PAA. The LDH nanosheets are uniformly wrapped by the light gray OCMCS-g-PAA. The edges of the sheets and the polymer phase interface are blurred, and there is no obvious phase separation boundary, indicating that there is a strong interaction between the two and excellent interfacial compatibility.
[0043] Figure 5 The figures are thermal analysis curves for Example 1 and Comparative Example 1, where... Figure 5 (a) TG plots of Example 1 and Comparative Example 1; Figure 5 (b) DTG diagrams for Example 1 and Comparative Example 1, derived from... Figure 5 It can be seen that, due to the complete dehydroxylation reaction and decomposition of interlayer anions in inorganic layers at high temperatures, the weight loss process is more sustained in the high-temperature region than in pure polymers. By comparing the two curves, it can be clearly found that the introduction of modified ZnAl-LDH slightly improves the thermal stability of the material. Modified ZnAl-LDH and OCMCS-g-PAA network achieve good composite. The layer barrier effect of modified ZnAl-LDH delays the thermal degradation behavior of the polymer.
[0044] Figure 6 The figures show the mechanical property test results for Examples 1, 2, and 1, where... Figure 6 (a) is the stress-strain curve. Figure 6(b) Young's modulus and tensile strength; OCMCS-g-PAA exhibits typical flexible polymer behavior with an elongation at break of up to 230%, but its tensile strength is only 2.1 MPa and its Young's modulus is 2.0 MPa; after the introduction of ZnAl-LDH, the tensile strength and Young's modulus of the composite system are significantly improved, while the elongation at break decreases. This is mainly because the ZnAl-LDH layer, as a rigid reinforcing phase, is uniformly dispersed in the matrix and transfers stress through interfacial hydrogen bonds and ionic bonds, thereby improving the strength of the composite material.
[0045] Figure 7 (a) is the particle size distribution diagram of LDH / OCMCS-g-PAA in Example 1. Figure 7 (b) is the particle size distribution diagram of DCF / LDH / OCMCS-g-PAA; the peak of the unloaded system (a) is narrow and high, indicating that the particles are uniformly dispersed and there is no obvious agglomeration, which corresponds completely to the morphology observed by TEM; the peak of the drug-loaded system (b) is slightly wider but still maintains a single peak. The increase in particle size is mainly attributed to the adsorption of DCF drug molecules on the surface of the composite particles. The single peak distribution of the drug-loaded system indicates that the drug loading process did not cause serious agglomeration of the particles. The composite material loaded with DCF drug in the examples is referred to as DCF / LDH / OCMCS-g-PAA.
[0046] Drug release application Drug release tests were conducted on Example 1 and Comparative Example 1, as detailed below: 276 nm was selected as the wavelength for subsequent standard curve establishment and quantitative detection of diclofenac (DCF) concentration in in vitro release experiments. A standard curve for DCF in PBS buffer solution at pH 7.4 was established, and the resulting fitting equation was: y = 0.0041 + 0.0312x, R0 2 =0.9997, DCF in vitro simulated drug release test was conducted, where, Figure 8 The figures show the drug release curves for Example 1, Comparative Example 1, and modified ZnAl-LDH.
[0047] Depend on Figure 8It can be seen that the modified ZnAl-LDH exhibits the fastest release rate and the highest cumulative release amount, with a significant burst release phenomenon occurring within the first 50 minutes, and a cumulative release rate of approximately 75%. When placed in the release medium, the medium molecules readily exchange with the drug, causing the drug molecules to rapidly detach from the LDH backbone, thus triggering an early burst release. In Comparative Example 1, the release rate of the pure OCMCS-g-PAA gel reached approximately 55%, and its initial burst release was significantly reduced compared to the modified ZnAl-LDH. In contrast, the release of the ZnAl-LDH / OCMCS-g-PAA composite material was the most gradual and slow, effectively suppressing the initial rapid release, with a cumulative release rate of approximately 48%. The results indicate that the ZnAl-LDH / OCMCS-g-PAA composite material, through the combination of modified ZnAl-LDH and carboxymethyl chitosan grafted polyacrylic acid polymer, successfully overcomes the excessively rapid burst release defect of modified ZnAl-LDH in drug delivery, achieving a more ideal and stable sustained drug release.
[0048] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.
Claims
1. A modified chitosan / layered double hydroxide composite material, characterized by, The composite material comprises a carboxymethyl chitosan-grafted polyacrylic acid polymer and an oleate-modified zinc-aluminum layered bimetallic hydroxide.
2. The modified chitosan / layered double hydroxide composite material according to claim 1, wherein The oleate-modified zinc-aluminum layered bimetallic hydroxide is dispersed in an intercalated form in a carboxymethyl chitosan-grafted polyacrylic acid polymer.
3. A method for preparing the modified chitosan / layered double hydroxide composite material according to claim 1 or 2, characterized by, The preparation method includes: Oleate-modified zinc-aluminum layered bimetallic hydroxide and carboxymethyl chitosan were dispersed in an aqueous solution, and then acrylic acid neutralizing solution was added. Under the action of an initiator and a crosslinking agent, an in-situ polymerization reaction was carried out to obtain the composite material.
4. The method for preparing the modified chitosan / layered bimetallic hydroxide composite material according to claim 3, characterized in that, The preparation method of the oleate-modified zinc-aluminum layered bimetallic hydroxide includes: dissolving potassium oleate, sodium carbonate and sodium hydroxide in deionized water, adding AlCl3·6H2O and ZnCl2 in sequence, stirring continuously to react, cooling to room temperature, filtering to obtain the precipitated solid, washing with deionized water 3-5 times, and finally vacuum drying to obtain the oleate-modified zinc-aluminum layered bimetallic hydroxide.
5. The method for preparing the modified chitosan / layered double hydroxide composite material according to claim 4, characterized in that, The molar ratio of potassium oleate, sodium carbonate and sodium hydroxide is 1:5:60; the molar ratio of potassium oleate:AlCl3·6H2O:ZnCl2 is 1:10:
20.
6. The method for preparing the modified chitosan / layered double hydroxide composite material according to claim 4 or 5, characterized in that, The stirring reaction temperature is 60-90℃, and the stirring reaction time is 1-3h.
7. The method for preparing the modified chitosan / layered double hydroxide composite material according to any one of claims 3-6, characterized in that, The in-situ polymerization reaction is carried out under an inert atmosphere, the reaction temperature is 50-80℃, and the reaction time is 10-20h.
8. The method for preparing the modified chitosan / layered double hydroxide composite material according to any one of claims 3-7, characterized in that, The mass ratio of carboxymethyl chitosan to acrylic acid is 1:2-10.
9. The method for preparing the modified chitosan / layered double hydroxide composite material according to any one of claims 3-8, characterized in that, The mass ratio of the oleate-modified zinc-aluminum layered bimetallic hydroxide to carboxymethyl chitosan is 1:10-50.
10. The application of the modified chitosan / layered bimetallic hydroxide composite material according to claim 1 or 2, or the modified chitosan / layered bimetallic hydroxide composite material prepared by the preparation method according to any one of claims 3-9, in drug release.