A zinc-adenine coordination assembled curcumin antibacterial dressing and a preparation method thereof

Abstract

This invention relates to the field of biomedical materials technology, specifically to a zinc-adenine coordination group-loaded curcumin antibacterial dressing and its preparation method. It constructs an antibacterial and enhanced dressing system through the triple synergistic effect of zinc, curcumin, and methacrylamide hyaluronic acid (HAMA) hydrogel.

Description

Technical Field

[0001] This invention relates to the field of biomedical materials technology, specifically to a zinc-adenine coordination group-loaded curcumin antibacterial dressing and its preparation method. Background Technology

[0002] Photocurable hydrogels have become mainstream materials in biomedical dressings and tissue engineering scaffolds due to their advantages such as rapid room-temperature molding, precise and controllable structure, and excellent biocompatibility. Among them, methacryloyl hyaluronic acid (HAMA) is one of the most representative photocurable matrices. It is obtained by modifying hyaluronic acid (HA) through methacrylation, retaining HA's high hydrophilicity, biodegradability, and cell affinity, while also endowing it with photoinitiated free radical cross-linking capabilities. In recent years, HAMA hydrogels have been widely used in wound repair and drug delivery systems; however, pure HAMA systems suffer from inherent limitations such as low porosity, limited functionality, and relatively weak mechanical properties.

[0003] To overcome functional limitations, metal-organic framework (MOF) composite hydrogels have become a research hotspot. Zinc-based MOFs (such as ZIF-8) are particularly important due to the presence of zinc (Zn). 2+ Zn-adenine's antibacterial activity and high drug loading potential have led to its widespread application. However, traditional Zn-adenine ligands, using 2-methylimidazole as a ligand, rely on high concentrations of 2-methylimidazole for coordination reactions (e.g., a molar ratio of 2-methylimidazole to metal ions greater than 10:1). This presents risks of cytotoxicity and requires high temperature and pressure (high-temperature solvothermal method, 80-140℃) for preparation, creating significant technical barriers when converting them into clinical medical products. Recently, research has shifted towards the endogenous ligand adenine to construct Zn-adenine MOFs, significantly improving biocompatibility.

[0004] Furthermore, curcumin, as a natural polyphenol, possesses broad-spectrum antibacterial, anti-inflammatory, and antioxidant activities, and is often used as a functional drug loaded onto MOF carriers. However, the traditional ZIF-8 high-temperature, high-pressure preparation method also leads to thermal degradation of the heat-sensitive drug curcumin, reducing its activity and drug loading efficiency.

[0005] Existing technologies also disclose the direct dispersion of traditional ZIF-8 nanoparticles in a hydrogel matrix to prepare wound dressings with antibacterial functions. For example, ZIF-8 is used as a carrier to load curcumin, silver ions, or antibiotics, and then combined with natural polymer hydrogels such as sodium alginate and gelatin, and the dressing is prepared through casting, electrospinning, or simple mixing processes. However, traditional hydrogel molding processes such as casting and electrospinning are difficult to precisely control (e.g., HAMA) the internal pore structure, resulting in poor exudate absorption capacity and cell infiltration efficiency of the dressing, as well as poor molding precision and structural controllability. When traditional ZIF-8 powder is macroscopically molded, it is prone to agglomeration leading to pore blockage, resulting in poor air permeability, weak exudate absorption capacity, and difficulty in matching the contours of irregular wounds, resulting in poor adherence.

[0006] Therefore, developing a novel dressing that is mild in preparation, structurally controllable, and possesses highly efficient synergistic antibacterial activity has become an urgent need in the industry. Summary of the Invention

[0007] The first aspect of this invention provides a method for in-situ synthesis of metal ion-adenine coordination group-loaded curcumin (Cur@Metal-Adenine) particles via coprecipitation, comprising a one-step drug loading via coprecipitation: rapid coordination precipitation of metal ions and adenine at room temperature, simultaneously encapsulating curcumin, comprising the following steps:

[0008] a) Prepare an ethanolic solution of curcumin (Cur) at a concentration of 0.5-10 mg / mL, preferably 1-5 mg / mL, for example 2 mg / mL;

[0009] b) Prepare an aqueous solution of adenine at a concentration of 1-50 mM, preferably 5-20 mM, for example 10 mM;

[0010] c) Prepare aqueous solutions of 1-100 mM, preferably 20-50 mM, metal ion salts;

[0011] d) Using neutral PBS or ultrapure water as the reaction substrate, adenine aqueous solution, metal ion solution and curcumin ethanol solution were added dropwise sequentially or simultaneously under room temperature and constant stirring conditions.

[0012] e) The reaction is carried out under constant temperature and continuous stirring for 1-3 hours. The coordination between metal ions and adenine rapidly leads to a co-precipitation reaction, which encapsulates curcumin in situ, forming a uniform Cur@Metal-Adenine particle suspension.

[0013] f) After washing and drying, Cur@Metal-Adenine particles are obtained.

[0014] In one embodiment, the metal ion is selected from Zn. 2+ Cu2+ or Mg 2+ wait.

[0015] In one implementation, after the reaction in step e) is completed, the precipitate is collected by centrifugation and repeatedly washed with deionized water or PBS to remove uncoordinated free ions, residual ligands and free curcumin.

[0016] The metal ion-adenine coordination group loaded curcumin (Cur@Metal-Adenine) particles of the first aspect of the present invention can be zinc-adenine coordination group loaded curcumin (Cur@Zn-Adenine) particles.

[0017] In one embodiment, the method for in-situ synthesis of zinc-adenine coordination group-loaded curcumin (Cur@Zn-Adenine) particles via coprecipitation in the first aspect includes a one-step drug loading via coprecipitation: rapid coordination precipitation of zinc with adenine at room temperature, simultaneously encapsulating curcumin, comprising the following steps:

[0018] a) Prepare an ethanolic solution of curcumin (Cur) at a concentration of 0.5-10 mg / mL, preferably 1-5 mg / mL, for example 2 mg / mL;

[0019] b) Prepare an aqueous solution of adenine at a concentration of 1-50 mM, preferably 5-20 mM, for example 10 mM;

[0020] c) Prepare 1-100 mM, preferably 20-50 mM, Zn-containing solutions. 2+ Solution;

[0021] d) Using neutral PBS or ultrapure water as the reaction substrate, under constant stirring conditions at room temperature, add dropwise sequentially or simultaneously the adenine aqueous solution prepared in step b) and the Zn-containing solution prepared in step c). 2+ The solution is the curcumin ethanol solution prepared in step a);

[0022] e) The reaction is carried out under constant temperature and continuous stirring for 1-3 hours. The coordination between zinc ions and adenine rapidly occurs in a co-precipitation reaction, which encapsulates curcumin in situ, forming a uniform Cur@Zn-Adenine particle mixed suspension.

[0023] f) After washing and drying, Cur@Zn-Adenine particles are obtained.

[0024] In one implementation scheme, Zn is included. 2+ The solutions were selected from Zn(NO3)2·6H2O solution, Zn(CH3COO)2·2H2O solution, ZnCl2 solution, and ZnSO4·7H2O solution.

[0025] In one embodiment, the curcumin loading of the zinc-adenine coordination group-loaded curcumin particles prepared in the first aspect of the present invention is ≥10%, preferably ≥15%, more preferably ≥20%, for example 24.2%.

[0026] In one embodiment, the curcumin used in the first aspect of the present invention may be replaced with antibacterial and anti-inflammatory drugs such as resveratrol, berberine, quercetin, gallic acid, chlorogenic acid, epigallocatechin gallate (EGCG), and kaempferol, as needed.

[0027] In one implementation, adenine may be replaced by other endogenous bases such as guanine, cytosine, or bioactive peptides such as arginylglycylaspartate peptide (RGD).

[0028] A second aspect of the present invention provides a method for loading a curcumin antibacterial dressing with a zinc-adenine coordination group, comprising the following steps:

[0029] 1) A method for in-situ synthesis of zinc-adenine coordination group-loaded curcumin particles by co-precipitation according to the first aspect of the present invention;

[0030] 2) The zinc-adenine coordination group-loaded curcumin particles synthesized in situ by coprecipitation in step 1) are uniformly dispersed in a solution of methacrylamide hyaluronic acid (HAMA).

[0031] 3) A zinc-adenine coordination group-loaded curcumin antibacterial dressing was prepared by photocuring crosslinking.

[0032] In one embodiment, the solvent in the methacryloyl hyaluronic acid (HAMA) solution is PBS buffer or sterile ultrapure water.

[0033] In one embodiment, the HAMA solution also contains a phenyl (2,4,6-trimethylbenzoyl) lithium phosphate photoinitiator (LAP photoinitiator).

[0034] In one embodiment, the concentration of the zinc-adenine coordination group-loaded curcumin particles in the HAMA solution is 0.1-10 mg / mL, preferably 0.5-5 mg / mL, more preferably 0.6-2 mg / mL, for example 1 mg / mL.

[0035] In one implementation, zinc-adenine coordination groups loaded with curcumin particles serve as physical fillers to expand the pores in the HAMA network, thereby achieving a structurally stable three-dimensional structure.

[0036] Beneficial effects:

[0037] 1) Achieve mild and efficient preparation: Use the adenine system to replace toxic ligands for curcumin loading, and combine room temperature precipitation with compounding. The reaction conditions are room temperature and normal pressure, without the need for high temperature and high pressure, which simplifies the process and reduces costs.

[0038] 2) Significantly improve structural stability: Construct a porous composite structure and combine it with 3D printing technology to provide a structured and precise dressing preparation process;

[0039] 3) Establish a powerful and synergistic antibacterial effect: Utilizing the triple synergistic effect of zinc ions, curcumin and hydrogel, it can kill pathogenic bacteria such as Staphylococcus aureus more quickly and efficiently, and promote tissue repair at the same time, covering the entire process from anti-infection to promoting healing.

[0040] definition

[0041] In this article, the term "metal ion-adenine coordination group loaded curcumin particles" can be abbreviated as "Cur@Metal-Adenine".

[0042] In this article, the terms "zinc-adenine coordination group loaded curcumin particles" have the same meaning as "Zn-adenine coordination group loaded curcumin particles", "Cur@Zn-Adenine", "Cur@Zn-Adenine particles", and "Cur@Zn-Adenine functional particles".

[0043] In this article, the terms "Zn-Adenine Coordination Group Loaded Curcumin Antibacterial Dressing" have the same meaning as "Zn-Adenine Coordination Group Loaded Curcumin Antibacterial Dressing", "Curcumin-Zn-Adenine-Methacrylamide Hyaluronic Acid Antibacterial Dressing", "Curcumin-Zn-Adenine-HAMA Antibacterial Dressing", "Cur@Zn-Adenine / HAMA Antibacterial Dressing", and "Cur@Zn-Adenine / HAMA". Attached Figure Description

[0044] Figure 1 The standard curve of curcumin concentration versus absorbance is shown (Y=0.1656-0.0048).

[0045] Figure 2 A macroscopic photograph of the curcumin-zinc-adenine-HAMA 3D-printed antibacterial dressing prepared in Example 2 is shown.

[0046] Figure 3 SEM images of the curcumin-zinc-adenine-HAMA 3D printed antibacterial dressing (b) prepared in Example 2 and the pure HAMA hydrogel antibacterial dressing (a) of Comparative Example 1 are shown.

[0047] Figure 4The antibacterial effects of the curcumin-zinc-adenine-HAMA 3D-printed antibacterial dressing prepared in Example 2 and various comparative materials are shown.

[0048] Figure 5 A schematic diagram of the preparation process of curcumin-zinc-adenine-HAMA 3D printed antibacterial dressing is shown. Detailed Implementation

[0049] The technical solutions in the examples of this invention will be clearly and completely described below. The specific embodiments listed below are only descriptions of the principles and features of this invention. The examples are only a part of this invention. All other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0050] Example 1: Preparation of Zinc-Adenine Coordination Group-Loaded Curcumin Particles by Coprecipitation Method

[0051] a) Solution preparation:

[0052] Preparation of curcumin (Cur) ethanol solution (2 mg / mL): Weigh 16 mg of curcumin powder using an analytical balance and transfer it to a centrifuge tube; add 8 mL of anhydrous ethanol and stir until the curcumin is completely dissolved to obtain a 2 mg / mL curcumin ethanol solution for subsequent drug loading. Aliquot as needed, wrap in aluminum foil / store in brown bottles at 4°C protected from light.

[0053] Preparation of adenine aqueous solution (10 mM): Accurately weigh 0.135 g of adenine powder using an analytical balance; pour the powder into a 100 mL beaker and add about 80 mL of ultrapure water; while stirring, add a small amount of 1 M HCl dropwise to aid dissolution; gently heat in a water bath at 40-50℃ and stir to accelerate dissolution; after complete dissolution and cooling to room temperature, transfer to a 100 mL volumetric flask and dilute to volume with ultrapure water; store at 4℃ for later use.

[0054] b) In-situ synthesis of zinc-adenine coordination group-loaded curcumin (Cur@Zn-Adenine) particles via coprecipitation method

[0055] Add 8 mL of adenine aqueous solution prepared in step a), 8 mL of curcumin ethanol solution prepared in step a), and 8 mL of Zn(NO3)2·6H2O solution (concentration 0.05 mol / L) in a volume ratio of 1:1:1, and then add 40 mL of PBS buffer. Stir at room temperature for 30 min. Purification and collection: Centrifuge at 800 rpm for 2 h, discard the supernatant; wash three times with deionized water to remove free ions and unencapsulated drug. Dry in a vacuum drying oven for 24 h to obtain 31.6 mg of Cur@Zn-Adenine solid powder, which is uniformly orange-yellow in color.

[0056] Determination of curcumin loading and encapsulation efficiency: First, a series of curcumin standard solutions of various concentrations were prepared using 95% ethanol as solvent. The absorbance was measured at 425 nm using a full-wavelength microplate reader to obtain the standard curve. Figure 1 (Y = 0.1656-0.0048), curcumin showed a good linear relationship with absorbance in the concentration range of 1 μg / mL-6 μg / mL. Subsequently, 10 mg of Cur@Zn-Adenine solid powder was taken and 10 mL of 95% ethanol was added. Curcumin was completely extracted by vortexing and sonication. After centrifugation and filtration, the sample was diluted 100 times with 95% ethanol and the absorbance was measured. The absorbance value was 0.3960. Substituting into the standard curve, the concentration of curcumin in the sample was calculated to be 2.42 μg / mL. Then, the drug loading (%) was calculated as 24.2% by the formula: (total mass of curcumin in zinc-adenine coordination group-loaded curcumin (Cur@Zn-Adenine) particles / total dry weight of particles) × 100%.

[0057] Example 2: Preparation of a zinc-adenine coordination group-loaded curcumin antibacterial dressing

[0058] a) Preparation of HAMA solution containing phenyl (2,4,6-trimethylbenzoyl) lithium phosphate photoinitiator (LAP photoinitiator)

[0059] Take 1 mL of PBS buffer and add it to a small centrifuge tube containing 2.5 mg of LAP photoinitiator; place it in a 40°C water bath for 15 min, shaking several times during this period to ensure complete dissolution of LAP, to obtain a 2.5 mg / mL LAP standard solution for later use. Weigh 20 mg of HAMA-150K (molecular weight 150K) powder and add it to the above LAP standard solution, mix well, to obtain a HAMA (2% (w / v), 20 mg / mL) solution containing LAP;

[0060] b) Prepare HAMA working solution containing Cur@Zn-Adenine

[0061] Add 1 mg of Cur@Zn-Adenine powder (mass ratio HAMA: Cur@Zn-Adenine = 20:1) in batches to 1 ml of HAMA solution containing LAP obtained in step a) to obtain a HAMA working solution of Cur@Zn-Adenine with a concentration of 1 mg / mL. Mix well and sonicate for 30 min until uniformly dispersed.

[0062] c) 3D printing photopolymerization

[0063] c-1: Equipment Inspection: Inspect the EFL-BP8601 Pro printer's power supply, light source (405nm blue light), lifting platform, and release film in the printing tray to ensure there is no damage or stains. Power on the printer to complete the self-test and enter biomedical printing mode, preheating for 5 minutes. Clean the printing tray and printing platform: wipe with anhydrous ethanol, rinse with sterile PBS, and allow to air dry for later use.

[0064] c-2: Equipment parameter settings and slicing: Open the EFL dedicated slicing software, import the hydrogel dressing STL model, center it, print layer thickness: 0.1mm, light source intensity: 12mW / cm², first layer exposure time: 25s (to enhance platform adhesion), normal layer exposure time: 12s, platform peeling speed: 8mm / min, platform lifting height: 2.5mm. After slicing, export the print file and transfer it to the EFL-BP8601 Pro printer.

[0065] c-3: Printing Operation Procedure: Select the automatic leveling mode. After completion, test the gap between the platform and the release film using A4 paper. Uniform resistance is acceptable. Slowly pour the prepared HAMA working solution containing Cur@Zn-Adenine into the material tank, ensuring the liquid surface covers the release film by 1-2mm with no air bubbles remaining. Retrieve the slice file, verify the parameters are correct, and then click "One-Click Print." Maintain the entire process with the door closed to avoid light. Observe the first layer's curing and adhesion, as well as the platform's lifting and peeling status. If any abnormalities occur, immediately pause and handle the issue. Printing Completion: The equipment automatically completes printing, the platform rises to its highest position, and the light source and lifting system are turned off.

[0066] c-4: Post-processing: Using a sterile plastic scraper, gently peel the hydrogel product from the edge of the printing platform, avoiding tearing and deformation. Immerse the gel in sterile PBS for 15 minutes, gently agitate and rinse, changing the PBS three times to remove uncured ink and residual initiator. Irradiate with 405nm blue light for 60 seconds to improve the cross-linking degree and mechanical stability of the hydrogel. Immerse in sterile PBS for 24 hours, changing the PBS every 6 hours to ensure sufficient swelling equilibrium. Store in sterile PBS at 4℃.

[0067] By following the steps above, you can obtain the curcumin-zinc-adenine-HAMA antibacterial dressing (Cur@Zn-Adenine / HAMA).

[0068] Comparative Example 1: Pure HAMA hydrogel antibacterial dressing

[0069] As a control material, a pure HAMA hydrogel antibacterial dressing was prepared.

[0070] The working solution used in the photocuring step is a HAMA (2% (w / v), 20 mg / mL) solution containing LAP, and the other steps remain unchanged.

[0071] Test Example 1: Appearance

[0072] The dressing has a regular three-dimensional structure, with a uniform pale yellow semi-transparent appearance. The surface is smooth, without obvious particle agglomeration or damage. It is soft and has a certain degree of elasticity, allowing it to bend slightly without breaking. The size of the dressing can be customized according to clinical needs (the sample size used in this experiment is 1cm×1cm×0.5cm). The edges are regular and burr-free, allowing it to closely conform to the contour of the wound. Its appearance is uniform, with no obvious delamination, bubbles, or impurities, which directly reflects the stability of the preparation process and the uniformity of the materials, meeting the appearance quality requirements of medical dressings. Figure 2 Macroscopic photographs of the curcumin-zinc-adenine-HAMA three-dimensional (3D) printed antibacterial dressing prepared in Example 2 are shown, demonstrating that the present invention can prepare medical antibacterial dressings with complete structure and regular morphology through 3D printing technology, solving the technical pain point that pure HAMA hydrogel is difficult to maintain complex three-dimensional structure.

[0073] Test Example 2: Microstructure

[0074] The microstructure of the curcumin-zinc-adenine-HAMA antibacterial dressing prepared in Example 2 and the pure HAMA hydrogel antibacterial dressing prepared in Comparative Example 1 were characterized, with three parallel samples for each sample.

[0075] For sample pretreatment, both types of samples were first cut into 1cm×1cm×0.5cm cubes and placed in a freeze dryer. They were freeze-dried at -80℃ and 10Pa vacuum for 48 hours until all moisture was removed. Fresh fracture surfaces were then obtained by brittle fracture under liquid nitrogen cooling. These fracture surfaces were fixed to the SEM sample stage with conductive adhesive and then sputter-coated with gold (15mA current, 80s time, gold thickness 5–10nm). For SEM observation, the SEM was preheated for 30 minutes to complete the self-test. The sample stage was then placed in the sample chamber and evacuated to a vacuum level ≥1×10⁻⁶. - For the ³Pa test, a secondary electron imaging mode was used, with an accelerating voltage of 5kV and a working distance of 8mm. Clear, artifact-free SEM images were captured at least three different fields of view for each sample at magnifications of 100× and 500×, and the images were saved in a standardized manner. For porosity determination, the 500× magnified SEM images were imported into ImageJ software. After desaturation, noise reduction, contrast adjustment, and binarization segmentation, the effective analysis area was selected, and the pore area was calculated in conjunction with the total image area. The porosity was then calculated using the formula, and the average value of the three fields of view for each sample was taken as the final result.

[0076] As attached Figure 3 As shown, compared with the pure HAMA hydrogel of Comparative Example 1 (see attached diagram) Figure 3 a) Cur@Zn-Adenine / HAMA composite hydrogel after compounding and pore-forming (with) Figure 3The SEM images of (b) show significantly superior microstructure and pore characteristics: the three-dimensional structure is clear and complete, forming a regular mesh network, with uniformly distributed internal pores and good pore connectivity, enabling the reaction of curcumin and Zn. 2+ With its three-dimensional loading, Cur@Zn-Adenine particles are uniformly dispersed in the mesh pores and framework, providing channels for sustained drug release.

[0077] Porosity measurements showed that the composite hydrogel had a porosity as high as 84.41% ± 0.29%. The core reason for the significant increase in porosity is that Cur@Zn-Adenine particles, acting as a physical filler, are uniformly dispersed in the HAMA crosslinking network, forming "support points" inside the hydrogel. This effectively expands the space between the HAMA molecular chains, avoiding structural shrinkage and collapse during the pretreatment process of pure HAMA hydrogels. At the same time, compared with pure HAMA hydrogels, Cur@Zn-Adenine particles form a weak interaction with the HAMA molecular chains, further stabilizing the three-dimensional network structure, ultimately forming a three-dimensional structure with high porosity and high connectivity.

[0078] Test Example 3: Antibacterial Performance

[0079] This embodiment evaluates the antibacterial activity of Cur@Zn-Adenine / HAMA-related samples against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) using the agar plate counting method. The specific experimental procedure is as follows:

[0080] Sample preparation: Sample A was 1 ml PBS (300 μl); Sample B was 2% HAMA solution (20 mg / ml, 300 μl); Sample C was 1 mg / ml Cur@Zn-Adenine PBS solution (300 μl); Sample D was Cur@Zn-Adenine / HAMA (containing 1 mg / ml 2% HAMA solution, 300 μl).

[0081] Escherichia coli and Staphylococcus aureus were inoculated separately into LB broth liquid medium to a final bacterial concentration of 10⁻⁶. 5 CFU·mL -1 Then, the sample addition operation was performed, taking 300 μl of samples A, B, C, and D respectively, and immersing them into 3 mL of the corresponding flat-top test tube with a concentration of 10. 5 CFU·mL -1The bacterial suspension was prepared as follows: The flat-topped test tubes containing the sample were placed in a shaker and incubated at 37°C and 120 rpm for 12 hours. After incubation, 100 μl of bacterial suspension from each group was evenly spread onto LB agar plates. The plates were then inverted and placed in an incubator at 37°C for 24 hours. Colonies on the plates were counted and photographed, and ImageJ software was used for image processing and analysis to evaluate the antibacterial properties of each sample.

[0082] like Figure 4 As shown, for the *Escherichia coli* group, the antibacterial rate of HAMA hydrogel was 74.67%, the antibacterial rate of Cur@Zn-Adenine particles was 62.49%, while the antibacterial rate of Cur@Zn-Adenine / HAMA was 94.21%. For the *Staphylococcus aureus* group, the antibacterial rate of HAMA hydrogel was 44.84%, the antibacterial rate of Cur@Zn-Adenine particles was 71.30%, while the antibacterial rate of Cur@Zn-Adenine / HAMA was 93.85%, showing a more significant synergistic antibacterial effect. These experimental results demonstrate that the antibacterial performance of the Cur@Zn-Adenine / HAMA composite hydrogel is significantly improved, confirming a significant synergistic antibacterial effect between the HAMA hydrogel matrix and the Cur@Zn-Adenine functional particles.

[0083] The above results indicate that the three-dimensional hydrogel network structure can effectively load and sustain the release of antibacterial active substances, significantly enhancing the inhibitory effect of the composite material on Escherichia coli and Staphylococcus aureus. This modification strategy effectively improves the antibacterial limitations of single materials, providing experimental support for its application in fields such as anti-infection wound repair and medical protective materials.

Claims

1. A method for in-situ synthesis of metal ion-adenine coordination group-loaded curcumin (Cur@Metal-Adenine) particles via coprecipitation, comprising a one-step drug loading via coprecipitation: rapid coordination precipitation of metal ions and adenine at room temperature, simultaneously encapsulating curcumin, comprising the following steps: a) Prepare an ethanolic solution of curcumin (Cur) at a concentration of 0.5-10 mg / mL, preferably 1-5 mg / mL, for example 2 mg / mL; b) Prepare an aqueous solution of adenine at a concentration of 1-50 mM, preferably 5-20 mM, for example 10 mM; c) The solutions prepared in steps a) and b) and the solutions containing metal ions are used to synthesize metal ion-adenine coordination group-loaded curcumin particles in situ by co-precipitation.

2. A method for in-situ synthesis of zinc-adenine coordination group-loaded curcumin (Cur@Zn-Adenine) particles via co-precipitation, comprising a co-precipitation drug loading step: Zn at room temperature 2+ Rapid coordination precipitation with adenine, simultaneously encapsulating curcumin, includes the following steps: a) Prepare an ethanolic solution of curcumin (Cur) at a concentration of 0.5-10 mg / mL, preferably 1-5 mg / mL, for example 2 mg / mL; b) Prepare an aqueous solution of adenine at a concentration of 1-50 mM, preferably 5-20 mM, for example 10 mM; c) Combine the solutions prepared in steps a) and b) with the Zn-containing solution. 2+ Zinc-adenine coordination group-loaded curcumin particles were synthesized in situ from the solution via co-precipitation.

3. The method according to claim 2, wherein step c) contains Zn. 2+ Zn in solution 2+ The concentration is 0.01-1.0 mol / L, preferably 0.02-0.5 mol / L, for example 0.05 mol / L.

4. The method according to claim 2 or 3, wherein the coprecipitation method in step c) includes a step of stirring the reaction at room temperature.

5. The method according to any one of claims 2-4, wherein the curcumin loading of the zinc-adenine coordination group-loaded curcumin particles is ≥10%, preferably ≥15%, more preferably ≥20%, for example 24.2%.

6. The method according to any one of claims 2-4, wherein it contains Zn 2+ The solutions were selected from Zn(NO3)2·6H2O solution, Zn(CH3COO)2·2H2O solution, ZnCl2 solution, and ZnSO4·7H2O solution.

7. A method for loading a zinc-adenine coordination group onto a curcumin antibacterial dressing, comprising the following steps: 1) The method for in-situ synthesis of zinc-adenine coordination group-loaded curcumin particles by co-precipitation according to claim 1; 2) The zinc-adenine coordination group-loaded curcumin particles synthesized in situ by coprecipitation in step 1) are uniformly dispersed in a solution of methacrylamide hyaluronic acid (HAMA). 3) A zinc-adenine coordination group-loaded curcumin antibacterial dressing was prepared by photocuring crosslinking.

8. The method according to claim 7, wherein the HAMA solution in step 2) further contains a phenyl (2,4,6-trimethylbenzoyl) lithium phosphate photoinitiator (LAP photoinitiator).

9. The method according to claim 7 or 8, wherein in step 2), the concentration of the zinc-adenine coordination group-loaded curcumin particles in the HAMA solution is 0.1-10 mg / mL, preferably 0.5-5 mg / mL, more preferably 0.6-2 mg / mL, for example 1 mg / mL.

10. The method according to any one of claims 7-9, wherein the photocuring in step 3) is performed by three-dimensional printing.

Images