Photothermal antibacterial hydrogel dressing for NIR-Ⅱ and preparation method and application thereof

Abstract

This invention provides a photothermal antibacterial hydrogel dressing for NIR-II, its preparation method, and its application. The preparation method involves mixing a 10%–15% PVA aqueous solution with an equal volume of other solutions, then mixing this mixture with CMCS and sodium tetraborate solution, stirring, and centrifuging to obtain the PBCM hydrogel. Each 1 ml of PVA solution corresponds to 40 mg of CMCS. The mass ratio of CMCS to sodium tetraborate solute is 10:1, and the solution concentration is greater than 0 μg / ml and less than or equal to 300 μg / ml. The hydrogel dressing prepared using this method exhibits mechanical strength, high swelling ratio (up to 798.45%), self-healing properties, and biocompatibility. Under low-power near-infrared II laser irradiation, it demonstrates a high antibacterial rate.

Description

Technical Field

[0001] This invention relates to the field of skin repair, specifically to a photothermal antibacterial hydrogel dressing for NIR-II (near-infrared 2nd zone), its preparation method, and its application. Background Technology

[0002] As the largest organ in the human body, the skin is highly susceptible to injury and bacterial infection, which can hinder the healing process. Therefore, minimizing the impact of infection is crucial. Current wound healing dressings, such as gauze, bandages, and hydrogels, often incorporate antibiotics to enhance healing. Hydrogels, with their three-dimensional structure, can absorb exudate, keep the wound moist, and reduce the risk of infection. While antibiotics are indispensable for treating bacterial infections, overuse can lead to antibiotic resistance. Therefore, there is an urgent need for an antibiotic-free hydrogel dressing that can modulate the wound microenvironment, absorb tissue exudate, and adapt to the dynamic wound surface to promote skin healing. Summary of the Invention

[0003] The technical problem to be solved by the present invention is to overcome the defects of existing hydrogel dressings containing antibiotics, and to provide a photothermal antibacterial hydrogel dressing for NIR-II (near-infrared 2nd region) and its preparation method and application. The hydrogel dressing can be used within the NIR-II window and has mechanical strength, high swelling ratio, self-healing properties, biocompatibility and excellent antibacterial properties.

[0004] The present invention solves the above-mentioned technical problems through the following technical solution: This invention provides a method for preparing a photothermal antibacterial hydrogel dressing for NIR-II, comprising: Mix 10%~15% PVA aqueous solution with an equal volume The solution is obtained by mixing the mixed solution with CMCS and sodium tetraborate solution, stirring, and centrifuging. Hydrogel; Each 1 ml of the PVA solution corresponds to 40 mg of the CMCS; The mass of the CMCS and the solute in the sodium tetraborate solution ( The mass ratio of (excluding water of crystallization) is 10:1; The The mass concentration of the solution is greater than 0 μg / ml and less than or equal to 300 μg / ml.

[0005] In this invention, the The solution can be prepared according to conventional methods in the art. Preferably, the... It is formed through electrostatic self-assembly, and the specific process is as follows: (1) Add 1.6 ml of 1 mg / ml mPEG-SH solution to 40 ml of AuNRs solution, stir for 24 hours, wash with deionized water, and then disperse the solution in 40 ml of deionized water to obtain solution A.

[0006] (2) Mix 5 ml of ethanol and 7 ml of deionized water with 3 ml of Nb2C solution, then add 300 μl of APTES, stir for 24 hours, wash the mixture and disperse it in 3 ml of deionized water to obtain solution B.

[0007] (3) Add 0.5 ml of solution B to 40 ml of solution A, stir for 2 hours, sonicate for 20 minutes, and then centrifuge at 7000 rpm to remove the supernatant, obtaining .

[0008] Among them, the It can be obtained in the manner conventional in the art, for example, by Obtained by hydrofluoric acid etching and TMAOH layering.

[0009] The AuNRs can be obtained through conventional methods in the art, for example, the specific preparation steps are as follows: (1) Under 35 ℃ conditions, take 0.5 mM Mix 5 mL of the solution thoroughly with 0.2 mM hexadecyltrimethylammonium bromide (CTAB) solution; add 1 mL of 6 μM [agent / concentrate] to the mixture. The solution was aged at 35 ℃ and allowed to stand for more than 0.5 h.

[0010] (2) Dissolve 3.5 g CTAB in 90 mL of water; dissolve 0.617 g sodium oleate (NaOL) in 35 mL of deionized water, then mix thoroughly with CTAB for 5 min; subsequently, add 12 mL of 4 mM silver nitrate to the mixed solution at 35 °C. The solution was left to stand for 15 minutes before being added. (125 ml, 0.001 M), and stirred at 800 rpm for 90 min. Then, 2.4 ml of concentrated hydrochloric acid was added and stirred evenly for 15 min. After that, 0.625 ml of 64 μM ascorbic acid AA solution and 200 μL of solution from step (1) were added every 0.5 min. The solution was then centrifuged and washed three times at 7000 rpm and stored at 4 ℃ in the dark.

[0011] In this invention, the PVA solution can be obtained in accordance with conventional methods in the art, for example, by dissolving PVA in deionized water and stirring at 600 rpm for 2 hours at 92 °C to obtain a 10%~15% PVA aqueous solution. Preferably, the concentration of the PVA aqueous solution is 12%.

[0012] In this invention, the The preferred mass concentration of the solution is 50 μg / ml, 100 μg / ml, 200 μg / ml or 300 μg / ml.

[0013] In this invention, the preferred method for preparing the hydrogel dressing is as follows: Mix 1 ml of 12% PVA solution with 1 ml of different concentrations The solutions were mixed, then 40 mg of CMCS was added to the resulting mixture and dissolved, followed by 400 μl of... Sodium tetraborate solution was used as a crosslinking agent. The mixture was stirred thoroughly to ensure uniform distribution, and then centrifuged to remove air bubbles, thus obtaining PBCM hydrogel.

[0014] The present invention also provides a hydrogel dressing prepared by the above-described preparation method for photothermal antibacterial hydrogel dressings for NIR-II.

[0015] In this invention, the Nb2C-AuNRs content in the hydrogel dressing is preferably 200 μg / ml.

[0016] The present invention also provides the application of the above-mentioned photothermal antibacterial hydrogel dressing for NIR-II in the preparation of dressings for treating drug-resistant bacterial infections.

[0017] In this invention, preferably, the dressing has a compatibility power of [missing information] during use. or NIR-II laser irradiation.

[0018] The positive and progressive effects of this invention are as follows: In this application, the PBCM hydrogel enhances its self-healing ability through the introduction of borate ester bonds. The PBCM hydrogel possesses mechanical strength, high swelling ratio (up to 798.45%), self-healing properties, and biocompatibility, promoting wound healing by regulating reactive oxygen species and adapting to dynamic surfaces. Under low-power near-infrared II laser irradiation, the PBCM hydrogel exhibits high antibacterial rates against *Escherichia coli* (up to 98.65%), extended-spectrum β-lactamase *Escherichia coli* (up to 97.21%), *Staphylococcus aureus* (up to 98.49%), and methicillin-resistant *Staphylococcus aureus* (up to 99.44%). Attached Figure Description

[0019] Figure 1 : Transmission electron microscope images and EDS elemental distribution images; Figure 2 Fourier transform infrared spectra of different hydrogel materials; Figure 3 : Photothermal temperature rise diagram of PBCM hydrogel; Figure 4 Statistical chart of the antibacterial activity of PBCM gel against methicillin-resistant Staphylococcus aureus. Detailed Implementation

[0020] The present invention will be further illustrated by way of embodiments below, but the present invention is not limited to the scope of the following embodiments.

[0021] The main reagents and materials used in the embodiments of this invention are as follows: Polyvinyl alcohol (PVA 1799) and carboxymethyl chitosan (CMCS) were purchased from McLean Technology Co., Ltd. (Purity ≥ 99%, 400 mesh) Purchased from Foshan Xinxi Technology Co., Ltd. Other reagents and materials not mentioned can be purchased in accordance with the conventional methods in this field.

[0022] Example 1 Synthesis

[0023] Exhibiting a dense multilayer structure, after 48 hours of hydrofluoric acid etching, the Al layer was removed, forming a multilayer structure with gaps. Then, by layering with TMAOH for 24 hours combined with ultrasonic vibration, a thinner layer with fewer layers was obtained. Nanosheets.

[0024] AuNRs, on the other hand, are synthesized using a conventional seed growth method in this field. The specific preparation steps are as follows: (1) Under 35 ℃ conditions, take 0.5 mM Mix 5 mL of the solution thoroughly with 0.2 mM hexadecyltrimethylammonium bromide (CTAB) solution; add 1 mL of 6 μM [agent / concentrate] to the mixture. The solution was aged at 35 ℃ and allowed to stand for more than 0.5 h.

[0025] (2) Dissolve 3.5 g CTAB in 90 mL of water; dissolve 0.617 g sodium oleate (NaOL) in 35 mL of deionized water, then mix thoroughly with CTAB for 5 min; subsequently, add 12 mL of 4 mM silver nitrate (NaOL) to the mixed solution at 35 °C. The solution was left to stand for 15 minutes before being added. (125 mL, 0.001 M), and stirred at 800 rpm for 90 min. Then, 2.4 mL of concentrated hydrochloric acid was added and stirred evenly for 15 min. After that, 0.625 mL of 64 μM ascorbic acid AA solution and 200 μL of solution from step (1) were added every 0.5 min. The solution was then centrifuged and washed three times at 7000 rpm and stored at 4 ℃ in the dark. AuNRs exhibited a rod-like structure with a length of 111.83 nm, a width of 18.94 nm, and an aspect ratio of 5.93 (e.g., ...). Figure 1 ).

[0026] It is formed through electrostatic self-assembly, and the specific process is as follows: (1) Add 1.6 ml of 1 mg / ml mPEG-SH solution to 40 ml of AuNRs solution, stir for 24 hours, wash with deionized water, and then disperse the solution in 40 ml of deionized water to obtain solution A.

[0027] (2) Mix 5 ml of ethanol and 7 ml of deionized water with 3 ml of... The solutions were mixed, and then 300 μl of APTES was added. After stirring for 24 hours, the mixture was washed and dispersed in 3 ml of deionized water to obtain solution B.

[0028] (3) Add 0.5 ml of solution B to 40 ml of solution A, stir for 2 hours, sonicate for 20 minutes, and then centrifuge at 7000 rpm to remove the supernatant, obtaining .

[0029] All of the above washing processes keep the resulting material solution near neutral.

[0030] Preparation of hydrogels (1) Dissolve PVA in deionized water and stir at 600 rpm for 2 hours at 92 °C to obtain a 12% PVA aqueous solution.

[0031] (2) Mix 1 ml of 12% PVA solution with 1 ml of 200 μg / ml PVA solution. The solutions were mixed. Then, 40 mg of CMCS was added to the resulting mixture and dissolved. Next, 400 μl of sodium tetraborate solution was added (…). Using [a specific agent] as a crosslinking agent, the mixture is thoroughly stirred to ensure uniform distribution, and then centrifuged to remove air bubbles. The final product obtained is the PBCM hydrogel, in which... The concentration in the hydrogel is 25 μg / ml.

[0032] Effect Example

[0033] I. Material Characterization TEM and EDS analyses confirmed that AuNRs in Uniform dispersion on the surface successfully prepared Composite materials ( Figure 1 ).

[0034] like Figure 2 As shown, PVA in The broad peak at that point is attributed to the stretching vibration of OH. PVA in The peak at 820°C is attributed to the stretching vibration of COC, and this peak weakens after condensation with borax (PB). PB at 820°C and... The changes in the peak value are attributed to the effects of BO stretching vibrations and the asymmetric stretching vibrations of the BOC bond. The addition of CMCS (PBC) affects... The changes in OH and NH peaks, PBC at 1600 and The peak at that point is caused by the asymmetric and symmetric stretching vibrations of -COOH. The functional groups (-OH, -F, and -O-) present on the surface can react with PVA and CMCS to form hydrogen bonds. However, The introduction of [the substance] did not significantly alter the FTIR spectrum of the PBCM hydrogel, indicating that it did not disrupt the PBC structure. [The following appears to be unrelated and possibly a separate sentence fragment:] In the composite material The addition of hydrophilic CMCS with carboxyl and amino groups also increases hydrophilic hydrogen bonds, thereby improving the swelling properties of the hydrogel.

[0035] After soaking in PBS buffer solution, the swelling percentage of the corresponding hydrogel increased from 510.86% (PB) to 794.72% (PBC40). However, after two hours of swelling, the CMCS content was... The PBC hydrogel (PBC40) exhibits structural instability due to its excessively large pore size. The CMCS content is... The hydrogel (PBC20) has a swelling ratio of 761.86%, exhibits structural stability, and can be used for subsequent experiments. PBCM has an average swelling ratio of 798.45%, exceeding that of PBC20 and PBC40. This enhanced swelling ratio facilitates the absorption of wound tissue fluid, thereby promoting healing.

[0036] II. Photothermal Properties of Materials (1) Add 0.5 ml of the solution to a small glass vial and irradiate it vertically with a 1064 nm laser. Analyze the solution using an infrared thermal imager (GUIDE, PS400) at the same concentration and laser power. AuNRs and .

[0037] At the same concentration ( Under the same power of 1.5 W and 1064 nm laser irradiation, It heats up to 62.2°C within 8 minutes. Its heating effect is higher than that of H2O (29.8°C). (53.5°C) and AuNRs (57.8°C). The enhanced photothermal conversion capability is attributed to Synergistic effect with AuNRs. Incorporating composite materials into PVA-CMCS enhances the photothermal properties of gel materials.

[0038] (2) Measure the heating effect under the same power density, when concentration hour( Figure 3 ), PBCM in It can rapidly heat to 54.5°C at a safe power level, demonstrating photothermal stability suitable for subsequent photothermal antibacterial research. Under the same conditions, The solution temperature only rose to 37.7°C after 8 minutes. This study demonstrates that PBCM materials exhibit good photothermal properties at low laser power.

[0039] III. Antibacterial Properties This study used Escherichia coli (E. coli), extended-spectrum β-lactamase Escherichia coli (ESB1-E. coli), Staphylococcus aureus (S. aureus), and methicillin-resistant Staphylococcus aureus (MRSA) to investigate the in vitro antibacterial activity of PBCM hydrogel materials.

[0040] The experiment included four groups: a blank control group, a PB group, a PBC group, and a PBCM group. The blank control group used physiological saline for the experimental procedures. Both sides of the hydrogel materials (PB, PBC, PBCM) were sterilized in water under UV light for 30 minutes inside centrifuge tubes, and then placed at the bottom of 2 ml centrifuge tubes. 500 μl of a solution with a concentration of [missing information] was added to the centrifuge tubes. The bacterial suspension was incubated with shaking at 250 rpm for 10 minutes, and then... The plates were irradiated with a 1064 nm laser at a certain power for 10 minutes. Afterward, they were incubated for 12-18 hours. Finally, the bacterial count was recorded by photographing. Each group was repeated three times.

[0041] This hydrogel material was used for photothermal antibacterial applications. Within 10 minutes, the sterilization effects of the blank control group, PB hydrogel, and PBC hydrogel were relatively limited under both laser irradiation and no irradiation conditions, with bacterial survival rates exceeding 90%. The observed higher bacterial survival rate in the experimental group compared to the blank control group is likely attributed to the hydrogel matrix providing nutrients to maintain bacterial viability. After being incorporated into the hydrogel, it exhibited a significant bactericidal effect even under conditions without laser irradiation. This effect can be attributed to the physical damage caused to bacteria by Nb2C and its influence on the microenvironment. The composite material also possesses photothermal properties, enabling it to kill bacteria at approximately 54°C. Results showed that... Under laser irradiation intensity, the antibacterial rates against *Escherichia coli*, extended-spectrum β-lactamase *Escherichia coli*, *Staphylococcus aureus*, and methicillin-resistant *Staphylococcus aureus* reached 98.65%, 97.21%, 98.49%, and 99.44%, respectively. Figure 4 These results indicate that PBCM hydrogels possess highly efficient bactericidal properties.

[0042] While specific embodiments of the present invention have been described above, those skilled in the art should understand that these are merely illustrative examples, and the scope of protection of the present invention is defined by the appended claims. Those skilled in the art can make various changes or modifications to these embodiments without departing from the principles and essence of the present invention, but all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A method for preparing a photothermal antibacterial hydrogel dressing for NIR-II, characterized in that, It includes: Mix 10%~15% PVA aqueous solution with an equal volume The PBCM hydrogel is obtained by mixing the mixed solution with CMCS and sodium tetraborate solution, stirring, and centrifuging. Each 1 ml of the PVA solution corresponds to 40 mg of the CMCS; The mass ratio of the CMCS to the sodium tetraborate solution solute is 10:

1. The The mass concentration of the solution is greater than 0 μg / ml and less than or equal to 300 μg / ml.

2. The method for preparing the photothermal antibacterial hydrogel dressing for NIR-II as described in claim 1, characterized in that, The It is formed through electrostatic self-assembly, and the specific process is as follows: (1) Add 1.6 ml of 1 mg / ml mPEG-SH solution to 40 ml of AuNRs solution, stir for 24 hours, wash with deionized water, and then disperse the solution in 40 ml of deionized water to obtain solution A; (2) Mix 5 ml of ethanol and 7 ml of deionized water with 3 ml of... The solutions were mixed, and then 300 μl of APTES was added. After stirring for 24 hours, the mixture was washed and dispersed in 3 ml of deionized water to obtain solution B. (3) Add 0.5 ml of solution B to 40 ml of solution A, stir for 2 hours, sonicate for 20 minutes, and then centrifuge at 7000 rpm to remove the supernatant, obtaining .

3. The method for preparing the photothermal antibacterial hydrogel dressing for NIR-II as described in claim 2, characterized in that, The The method to obtain it is: Obtained by hydrofluoric acid etching and TMAOH layering.

4. The method for preparing the photothermal antibacterial hydrogel dressing for NIR-II as described in claim 1, characterized in that, The PVA solution was obtained as follows: PVA was dissolved in deionized water and stirred at 600 rpm for 2 hours at 92 °C to obtain a 10%~15% PVA aqueous solution.

5. The method for preparing the photothermal antibacterial hydrogel dressing for NIR-II as described in claim 4, characterized in that, The concentration of the PVA aqueous solution is 12%.

6. The method for preparing the photothermal antibacterial hydrogel dressing for NIR-II as described in claim 1, characterized in that, The The mass concentration of the solution is 50 μg / ml, 100 μg / ml, 200 μg / ml or 300 μg / ml.

7. The method for preparing the photothermal antibacterial hydrogel dressing for NIR-II as described in claim 1, characterized in that, The preparation method of the hydrogel dressing is as follows: Mix 1 ml of 12% PVA solution with 1 ml of different concentrations The solutions were mixed, then 40 mg of CMCS was added to the resulting mixture and dissolved, followed by 400 μl of... Sodium tetraborate solution was used as a crosslinking agent. The mixture was stirred thoroughly to ensure uniform distribution, and then centrifuged to remove air bubbles, thus obtaining PBCM hydrogel.

8. A hydrogel dressing prepared by the method for preparing photothermal antibacterial hydrogel dressing for NIR-II according to any one of claims 1 to 7.

9. The use of the photothermal antibacterial hydrogel dressing for NIR-II as described in claim 8 in the preparation of dressings for treating drug-resistant bacterial infections.

10. The application of the photothermal antibacterial hydrogel dressing for NIR-II as described in claim 9 in the preparation of dressings for treating drug-resistant bacterial infections, characterized in that, The dressing has a compatibility power of [missing information] during use. or NIR-II laser irradiation.

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