An antibacterial dressing driven by photothermal effect and a preparation method thereof

Abstract

The application discloses a kind of photothermal driven antibacterial dressings and preparation method thereof, belong to medical material technical field.The antibacterial dressing includes: with hyaluronic acid hydrogel as carrier, load MXene / metal ion nanoparticles, the MXene / metal ion nanoparticles are formed by single sheet MXene and metal ion mixed zeta potential close to neutral nanoparticles.The antibacterial dressing provided by the application is hydrogel dosage form, depends on the photo-thermal conversion performance of MXene / metal ion nanoparticles, can effectively convert near infrared light into heat, rapidly heats up, sterilization is carried out by the temperature of wound place, safe and no side effect;And hydrogel can effectively form protective layer at wound place, block the adverse effects of external environment on wound surface, and the antiseptic and antibacterial performance is good.The antibacterial dressing preparation method is simple, easy to mass production.

Description

Technical Field

[0001] This invention relates to the field of medical materials technology, specifically to a photothermal effect-driven antibacterial dressing and its preparation method. Background Technology

[0002] As the largest organ and first line of defense in the human body, the skin plays a vital role in protecting the internal environment from external damage. Once the skin is damaged and loses its original defensive function, the subcutaneous tissue becomes susceptible to microbial invasion, leading to infection and seriously affecting people's lives and health. If the patient has underlying diseases, such as diabetes, it is prone to chronic wounds, and repeated treatments can easily lead to the emergence of drug-resistant bacteria.

[0003] Currently, the treatment of infected wounds primarily involves debridement dressings. Traditional dressings typically have a loose, sponge-like lower layer that absorbs exudate and promotes tissue regeneration, while the upper layer uses polyurethane to isolate external irritants and prevent microbial invasion. However, traditional skin dressings generally lack antibacterial properties, allowing residual bacteria in the wound to proliferate and create intractable wounds. To achieve antibacterial properties, some dressings incorporate antibiotics, nano-silver, and other antibacterial agents. However, the overuse of these antibacterial agents often carries a degree of biotoxicity, and antibiotic abuse has led to the prevalence of drug-resistant bacteria. Therefore, developing antibiotic-free antibacterial dressings is crucial for wound protection and infection control.

[0004] MXenes (a collective term for transition metal carbides and nitrides) are a new type of two-dimensional nanomaterials with the general formula M. n+ 1X n T x (n = 1 to 3), where M is a pre-transition metal element, X is carbon or nitrogen, and T refers to active functional groups such as fluorine, hydroxyl, or oxygen groups bonded to the surface of the material. These materials possess ultrathin structures and excellent physicochemical (electronic, optical, magnetic, etc.) properties. Currently, MXene's applications in the biomedical field are gradually expanding, mainly due to its large surface area and strong absorption in the near-infrared region, coupled with its ability to be easily modified and combined with various molecules or nanoparticles.

[0005] Patent document CN 112915251 A discloses a biopolymer fiber wound dressing, which uses polycaprolactone, polylactic acid or polyvinyl alcohol as a carrier to load MXene, chitosan and anti-inflammatory drugs to form a biopolymer fiber wound dressing with antibacterial and anti-inflammatory properties. This dressing combines the photothermal and photodynamic bactericidal effect of the two-dimensional material MXene with the bacterial adsorption effect of biopolymer fibers to reduce the risk of bacterial infection of wounds.

[0006] Patent document CN 114344544 A discloses a photoactivated antibacterial dressing, the preparation method of which includes: S1, etching MAX ceramic into MXene nanosheets; S2, preparing MXene / Ag3PO4 heterojunctions or MXene / AgS heterojunctions; S3, modifying the heterojunctions with polydopamine; S4, dissolving, mixing and forming a film between polycaprolactone particles and polydopamine-modified MXene / Ag3PO4 or MXene / AgS heterojunctions to obtain a nanofiber membrane.

[0007] The existing reports on the preparation process of antibacterial dressings using MXene two-dimensional materials are relatively complex, requiring advanced film-forming equipment, which is not conducive to industrial production. Summary of the Invention

[0008] The purpose of this invention is to provide an antibacterial dressing that is simple to prepare and suitable for large-scale production. This antibacterial dressing can effectively convert near-infrared light into heat, rapidly raise the temperature for sterilization, and has good antiseptic and antibacterial properties.

[0009] To achieve the above objectives, the present invention adopts the following technical solution:

[0010] This invention provides a photothermal effect driven antibacterial dressing, the antibacterial dressing comprising: MXene / metal ion nanoparticles loaded on a hyaluronic acid hydrogel as a carrier, wherein the MXene / metal ion nanoparticles are nanoparticles with a zeta potential close to electroneutrality (-1.5mV≤zeta potential≤+1.5mV) formed by mixing monolayer MXene with metal ions.

[0011] This invention reveals that monolayer MXene two-dimensional materials aggregate with metal ions through electrostatic adsorption, forming nanoparticles. The increased particle size of these nanoparticles enhances their absorption of near-infrared light, rapidly converting it into heat for fast photothermal sterilization. The zeta potential of the MXene nanoparticles fully loaded with metal ions is close to electroneutrality.

[0012] The metal ions can be copper ions, manganese ions, iron ions, ferrous ions, silver ions, etc.

[0013] Preferably, the metal ion is a copper ion. Cu 2+ Electrostatic adsorption onto the MXene surface; during the contact between the nanoparticles and the skin, Cu... 2+ It can be slowly released onto the skin wound, promoting blood vessel regeneration and thus promoting skin regeneration and repair.

[0014] This invention uses hyaluronic acid hydrogel as a carrier for loading MXene / metal ion nanoparticles, and the prepared antibacterial dressing is a hydrogel formulation. Hyaluronic acid is an acidic mucopolysaccharide with good biocompatibility. When used as a skin dressing, it protects the skin. The hydrogel can effectively form a protective layer at the wound site, blocking the adverse effects of the external environment on the wound.

[0015] The present invention also provides a method for preparing the above-mentioned photothermal driven antibacterial dressing, the method comprising the following steps:

[0016] (1) MAX ceramic is etched into a single layer of MXene, and then dispersed in water to obtain an MXene aqueous solution. Metal ion solution is added dropwise under stirring, and the precipitate is collected to obtain MXene / metal ion nanoparticles.

[0017] (2) MXene / metal ion nanoparticles were added to oxidized hyaluronic acid solution and hydrazide-grafted hyaluronic acid solution respectively, and the two mixtures were then mixed to form a gel to obtain the antibacterial dressing.

[0018] In step (1), MAX ceramic is immersed in an etching solution and continuously stirred at room temperature to etch it into a monolayer material. Then, the monolayer MXene two-dimensional material is ultrasonically dispersed in water, metal ions are added, and the metal ions are electrostatically adsorbed on the MXene surface. At the same time, the monolayer aggregates to form nanoparticles with a diameter of 1000-2000 nm.

[0019] The MAX ceramic can be Ti3AlC2, Ti2AlC, Ta4AlC3, etc.

[0020] Preferably, the MAX ceramic is etched into a single layer of MXene using a lithium fluoride / hydrochloric acid (LiF / HCl) etching method.

[0021] Specifically: Ti3AlC2 is soaked in lithium fluoride / hydrochloric acid solution and stirred continuously for 48-96 hours. The precipitate is collected and washed with water until neutral. The precipitate is then added to water, nitrogen gas is bubbled in, and the mixture is sonicated at 50-150 kHz for 5-20 minutes. The sonicated solution is then centrifuged at 2000-4000 rpm for 0.5-1.5 hours. The supernatant is collected and dried to obtain monolayer MXene.

[0022] Preferably, the metal ion solution is a copper chloride solution with a concentration of 2-6M. More preferably, the copper chloride solution has a concentration of 5M.

[0023] Preferably, 0.4 mL of 5M copper chloride solution is added to every 50 mg of monolayer MXene, and the mixture is then centrifuged at 3500 rpm for 10 min to collect the precipitate.

[0024] In step (2), MXene / metal ion nanoparticles are uniformly dispersed at equal concentrations in oxidized hyaluronic acid solution and hydrazide-grafted hyaluronic acid solution, respectively. The two mixtures are then combined, and a cross-linking reaction is achieved between the aldehyde groups of oxidized hyaluronic acid and the hydrazide groups of hydrazide-grafted hyaluronic acid to form a hydrogel. The MXene / metal ion nanoparticles are uniformly distributed in the hydrogel.

[0025] Preferably, the method for preparing the oxidized hyaluronic acid includes: using a 5×10⁻⁶ molecular weight hyaluronic acid... 5 Hyaluronic acid is dissolved in water, sodium periodate is added, and the mixture is stirred in the dark for 2-6 hours. After dialysis, oxidized hyaluronic acid is obtained.

[0026] The mass ratio of hyaluronic acid to sodium periodate was 1:5. After the reaction was completed, dialysis was performed using a dialysis bag with a molecular weight cutoff of 3500 to remove excess sodium periodate.

[0027] Preferably, the preparation method of the hydrazide-grafted hyaluronic acid includes: using a hydrazide with a molecular weight of 1×10⁻⁶ to graft hyaluronic acid onto a hydrazide grafted ... 5 Hyaluronic acid was dissolved in MES buffer, and excess adipic acid dihydrazide was added. After the reaction was complete, the mixture was dialyzed to obtain hydrazide-grafted hyaluronic acid.

[0028] The mass ratio of hyaluronic acid to adipic acid dihydrazide was 1:5, and the reaction was allowed to proceed for 24 hours. After the reaction was complete, dialysis was performed using a dialysis bag with a molecular weight cutoff of 3500 to remove excess salt.

[0029] Preferably, in the gelation reaction system, MXene / Cu 2+ The final concentration of nanoparticles was 150 μg / mL, the final concentration of oxidized hyaluronic acid was 1%, and the final concentration of hydrazide-grafted hyaluronic acid was 4%. The hydrogel prepared under the above ratio conditions exhibited good mechanical strength.

[0030] The photothermal effect driven antibacterial dressing provided by this invention exerts a phototherapy effect under near-infrared light irradiation, and therefore can be developed into a near-infrared photothermal therapy preparation.

[0031] The beneficial effects of this invention are as follows:

[0032] (1) The antibacterial dressing provided by the present invention relies on the photothermal conversion performance of MXene / metal ion nanoparticles, which can effectively convert near-infrared light into heat, rapidly raise the temperature, and sterilize by raising the temperature of the wound, which is safe and has no side effects.

[0033] (2) The antibacterial dressing provided by the present invention is an injectable hydrogel formulation, which can be used as needed, is clean, hygienic and convenient, and the hydrogel can effectively form a protective layer on the wound, blocking the adverse effects of the external environment on the wound surface, and has good antiseptic and antibacterial properties.

[0034] (3) The method for preparing antibacterial dressings provided by the present invention is simple and easy to mass-produce. Attached Figure Description

[0035] Figure 1 This is a transmission electron microscope image of the MXene monolayer in Example 1.

[0036] Figure 2 This is a particle size distribution diagram of the MXene monolayer prepared in Example 1.

[0037] Figure 3 MXene / Cu prepared in Example 1 2+ Zeta potential diagram of nanoparticles.

[0038] Figure 4 MXene / Cu prepared in Example 1 2+ Scanning electron microscope image of nanoparticles.

[0039] Figure 5 MXene / Cu prepared in Example 1 2+ Particle size distribution diagram of nanoparticles.

[0040] Figure 6 The rheological results are shown for the gels formed by mixing oxidized hyaluronic acid solution and hydrazide-grafted hyaluronic acid solution at different concentrations. H2O1, H3O1, and H4O1 represent the gel groups formed by mixing 2% oxidized hyaluronic acid solution and 4%, 6%, and 8% hydrazide-grafted hyaluronic acid solutions at a volume ratio of 1:1.

[0041] Figure 7 Contains 150 μg / mL MXene / Cu 2+ Rheological results of hydrogels containing nanoparticles.

[0042] Figure 8 For different concentrations of MXene / Cu 2+ Photothermal conversion efficiency of hydrogels containing nanoparticles.

[0043] Figure 9 Contains 150 μg / mL MXene / Cu 2+ Photothermal cycling results of nanoparticle hydrogels.

[0044] Figure 10 The figure shows the Tyndall effect detection results for MXene dispersions. From left to right, the figures are MXene / Cu. 2+ Nanoparticle suspension, monolayer MXene suspension, deionized water.

[0045] Figure 11 Contains 150 μg / mL MXene / Cu 2+The antibacterial effect of nanoparticle hydrogels on Escherichia coli and Staphylococcus aureus. Detailed Implementation

[0046] The present invention will be further described below with reference to specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Any modifications or substitutions made to the methods, steps, or conditions of the present invention without departing from the spirit and essence of the invention are within the scope of the invention.

[0047] Unless otherwise specified, the experimental methods used in the following examples are conventional methods; the materials and reagents used are commercially available unless otherwise specified.

[0048] Example 1

[0049] I. Preparation of Antibacterial Dressings

[0050] 1. MXA etching produces monolayer MXene.

[0051] The etching method using lithium fluoride / hydrochloric acid (LiF / HCl) was as follows: 2g of LiF powder was added to 30mL of 5-8M hydrochloric acid solution. After it was completely dissolved, 2g of Ti3AlC2 was slowly added and the mixture was stirred with strong magnetic force at room temperature for 48 hours.

[0052] After the reaction was complete, the mixture was centrifuged at 3500 rpm for 5 min, the precipitate was collected, washed with water, and repeated several times until the supernatant was neutral, and the precipitate was collected again. The precipitate was added to 30 mL of deionized water, nitrogen gas was bubbled in, and the mixture was sonicated at 100 kHz for 10 min. Finally, the sonicated solution was centrifuged at 3500 rpm for 1 hour, and the supernatant was collected and freeze-dried. The resulting blackish-green solid was a monolayer MXene material.

[0053] like Figure 1 As shown, TEM results indicate that MXene is a monolayer. The particle size of the MXene sheets is approximately 240 nm. Figure 2 ).

[0054] 2. MXene / Cu 2+ Preparation of nanoparticles

[0055] 50 mg of monolayer MXene was redispersed in 20 mL of deionized water by sonication. 5 M CuCl2 solution was added dropwise under magnetic stirring at room temperature. After adding 0.1 mL, 0.2 mL, 0.3 mL, 0.4 mL, and 0.5 mL of CuCl2 solution, the solution was centrifuged at 3500 rpm for 10 minutes. The precipitate was collected and analyzed for zeta potential (corresponding to zeta potentials of -34.1 mV, -18.3 mV, -6.6 mV, -0.7 mV, and +5.2 mV).

[0056] The results are as follows Figure 3 As shown, the group with the zeta potential closest to electroneutrality was selected as the optimal group (0.4 mL group), and the precipitate obtained from this group was MXene / Cu. 2+ Nanoparticles were freeze-dried and stored for later use.

[0057] like Figure 4 As shown, the SEM results indicate that Cu 2+ / MXene consists of nano-aggregate particles. Particle size analysis shows that Cu 2+ / MXene particle size is approximately 1200nm ( Figure 5 This result indicates that Cu 2+ It effectively promotes the aggregation of MXene, which is beneficial to the photothermal effect.

[0058] 3. Preparation of oxidized hyaluronic acid

[0059] 1g of hyaluronic acid (molecular weight of 500,000) is completely dissolved in 50mL of deionized water. After adding 5g of sodium periodate, the mixture is stirred magnetically for 2-6 hours in the dark. The reaction solution is then placed in a dialysis bag with a molecular weight cutoff of 3500 Da. After dialysis with deionized water for 1-3 days, the solution is freeze-dried to obtain oxidized hyaluronic acid.

[0060] 4. Preparation of hyaluronic acid grafted with hydrazide

[0061] 1g of hyaluronic acid (molecular weight of 100,000) was completely dissolved in 100mL of 2-morpholinoethanesulfonic acid (MES) buffer, and 5g of adipic acid dihydrazide powder was added. The mixture was allowed to react for 24 hours. The reaction solution was then placed in a dialysis bag with a molecular weight cutoff of 3500 Da. After dialysis with deionized water for 1-3 days, the solution was freeze-dried to obtain hydrazide-grafted hyaluronic acid.

[0062] 5. Preparation of antibacterial dressing hydrogel

[0063] 5.1 Prepare a 2% oxidized hyaluronic acid solution and 4%, 6%, and 8% hydrazide-grafted hyaluronic acid solutions. Mix the two solutions at a volume ratio of 1:1 using a dual-chamber syringe and inject them into the mold to form a gel. Perform rheological tests.

[0064] The results are as follows Figure 6 As shown, the H4O1 group (a mixture of 2% oxidized hyaluronic acid solution and 8% hydrazide-grafted hyaluronic acid) exhibited the best mechanical strength and was the preferred candidate for subsequent MXene / Cu gel formation. 2+ Loading platform for nanoparticles.

[0065] 5.2 Preparation of MXene / Cu containing 150 μg / mL 2+ 2% oxidized hyaluronic acid solution of nanoparticles and MXene / Cu containing 150 μg / mL 2+ An 8% hydrazide-grafted hyaluronic acid solution containing nanoparticles was used. The two solutions were then mixed at a 1:1 volume ratio and injected into a mold using a dual-chamber syringe to form a gel. The resulting antibacterial dressing hydrogel contained MXene / Cu. 2+ The final concentration of nanoparticles was 150 μg / mL, the final concentration of oxidized hyaluronic acid was 1%, and the final concentration of hydrazide-grafted hyaluronic acid was 4%.

[0066] II. Performance Characterization

[0067] 1. Rheological results

[0068] like Figure 7 As shown, the results indicate that MXene / Cu 2+ The loading of nanoparticles can improve the mechanical properties of this hydrogel to some extent. Rheological results show that the resulting hydrogel dressing has a stable structure.

[0069] 2. Photothermal conversion

[0070] For different MXene / Cu loading concentrations 2+ The hyaluronic acid hydrogel with nanoparticles was subjected to a 1.2 W / cm² reaction. 2 The hydrogel was irradiated with 808nm near-infrared light, and the temperature changes were recorded in real time.

[0071] The results are as follows Figure 8 As shown, with MXene / Cu 2+ The photothermal conversion efficiency of the hydrogel increases with the increase in the amount of nanoparticles added.

[0072] Photothermal conversion results showed that 1 mL of hydrogel had a thermal efficiency of 1.2 W / cm². 2 After 10 minutes of NIR, the temperature rose significantly, increasing by 38 degrees Celsius (DT) from room temperature within 10 minutes. This demonstrates excellent heat generation, resulting in a good antibacterial effect.

[0073] 3. Photothermal cycle

[0074] Choose MXene / Cu containing 150 μg / mL 2+ The nanoparticle hydrogel was used as the experimental group, and it was subjected to 1.2 w / cm for 10 min.2 After being irradiated with 808nm near-infrared light, the hydrogel was naturally cooled to room temperature, and the temperature change of the hydrogel was recorded in real time. Three cycles of testing were conducted to observe the stability of the photothermal conversion of the hydrogel.

[0075] The results are as follows Figure 9 As shown, the hydrogel exhibits a good heating process under near-infrared light irradiation, can cool down rapidly after the near-infrared light is removed, and has good cycling stability.

[0076] The photothermal cycling results show that the material has good photothermal conversion efficiency and stability.

[0077] 4. Tyndall effect in MXene dispersions

[0078] MXene / Cu irradiated with laser 2+ Nanoparticle suspensions, monolayer MXene suspensions, and deionized water were used to observe whether a clear optical path could be observed when the laser passed through the solution. If a clear optical path was observed, it indicated that there were uniformly dispersed nanoparticles in the solution.

[0079] The results are as follows Figure 10 As shown, the Tyndall effect was observed in the MXene dispersion, exhibiting typical colloidal solution characteristics, which is conducive to the uniform distribution of substances.

[0080] 5. Determination of the antibacterial activity of the antibacterial hydrogel

[0081] Antibacterial dressing hydrogel was spread on a 96-well plate and incubated with Escherichia coli solution or Staphylococcus aureus for 1–3 hours. After irradiation with NIR for 6 minutes, 2–5 μL of the solution was diluted with PBS buffer and spread evenly on LB solid culture plates containing agar. After incubation at 37°C for 16–18 hours, bacterial colony growth was observed.

[0082] like Figure 11 As shown, when the antibacterial hydrogel was co-incubated with Escherichia coli solution or Staphylococcus aureus solution, no bacterial colonies appeared, indicating that the antibacterial hydrogel has excellent activity against Gram-negative bacteria and Gram-positive bacteria.

Claims

1. A photothermal effect driven antibacterial dressing, characterized in that, The antibacterial dressing comprises hyaluronic acid hydrogel as a carrier, loaded with MXene / metal ion nanoparticles, the MXene / metal ion nanoparticles are nanoparticles with zeta potential ≥-1.5 mV and ≤+1.5 mV formed by mixing single-layer MXene and metal ions; the metal ion is copper ion; The preparation method of the antibacterial dressing comprises the following steps: (1) etching MAX ceramic into single-layer MXene, then dispersing in water to obtain MXene aqueous solution, adding metal ion solution under stirring condition, collecting precipitate, which is MXene / metal ion nanoparticles; (2) adding MXene / metal ion nanoparticles into oxidized hyaluronic acid solution and hydrazide grafted hyaluronic acid solution respectively, then mixing the two mixed liquids, and forming gel to obtain the antibacterial dressing; in the gel reaction system, the final concentration of MXene / metal ion nanoparticles is 150 μg / mL; the final concentration of oxidized hyaluronic acid is 1%, and the final concentration of hydrazide grafted hyaluronic acid is 4%; The method for preparing the oxidized hyaluronic acid comprises: dissolving hyaluronic acid with a molecular weight of 5×10 5 in water, stirring in the dark for 2-6 hours after adding sodium periodate, dialyzing, and obtaining the oxidized hyaluronic acid. The method for preparing the hydrazide grafted hyaluronic acid comprises: dissolving hyaluronic acid with a molecular weight of 1×10 5 in MES buffer, adding excessive adipic acid dihydrazide, fully reacting, and dialyzing to obtain hydrazide grafted hyaluronic acid.

2. The photothermally driven antibacterial dressing of claim 1, wherein, In step (1), MAX ceramic is etched into single-layer MXene by lithium fluoride / hydrochloric acid etching method.

3. The photothermally effected driven antibacterial dressing of claim 2, wherein, Ti3AlC2 is immersed in lithium fluoride / hydrochloric acid solution, and continuous stirring is carried out for 48-96 hours, then the precipitate is collected and washed with water to neutral; then the precipitate is added into water, nitrogen is blown in, ultrasonic treatment is carried out under the condition of 50-150 KHz for 5-20 minutes, then the ultrasonic treated solution is centrifuged under the condition of 2000-4000 rpm for 0.5-1.5 hours, the supernatant is collected, and drying is carried out to obtain single-layer MXene.

4. The photothermally effected driven antibacterial dressing of claim 1, wherein, In step (1), the metal ion solution is copper chloride solution with a concentration of 2-6 M.

5. The photothermally effected driven antibacterial dressing of claim 4, wherein, In step (1), 0.4 mL of 5 M copper chloride solution is added to every 50 mg of single-layer MXene, and then the mixed solution is centrifuged to collect the precipitate.

6. Application of the photothermal effect driven antibacterial dressing according to any one of claims 1-5 in the preparation of near-infrared photothermal treatment preparation.

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