Temperature self-limiting controllable drug release light-heat hydrogel film and preparation method thereof

Abstract

The invention discloses a temperature self-limiting type controllable drug release light-heat hydrogel film and a preparation method thereof, and relates to the field of light-heat hydrogel films, the method comprises the following steps: S1, packaging a phase change material and a drug in three-dimensional ordered macroporous carbon together to obtain OMCP; s2, modifying the OMCP by adopting a dopamine substance, so as to obtain OMCPA; and S3, mixing the OMCPA with acrylamide, a cross-linking agent and an initiator, adding an accelerant, and carrying out cross-linking polymerization reaction in an ice-water bath to obtain the temperature self-limited controllable drug release photo-thermal hydrogel film. According to the three-dimensional ordered macroporous carbon, the photo-thermal stability is remarkably improved, the leakage risk is avoided, the three-dimensional ordered macroporous structure provides stable framework support for the three-dimensional ordered macroporous carbon, the three-dimensional ordered macroporous carbon serves as a photo-thermal material, the photo-thermal performance does not need to be maintained by depending on the chemical structure stability of a traditional photosensitizer, and the three-dimensional ordered macroporous carbon can be used as a photo-thermal material. And the problem that the photo-thermal stability is reduced due to chemical degradation or structural damage of photosensitizer molecules in photo-thermal circulation is avoided.

Description

Technical Field

[0001] This invention relates to the field of photothermal hydrogel membranes, specifically a temperature-self-limiting, controllable drug release photothermal hydrogel membrane and its preparation method. Background Technology

[0002] As the outermost protective barrier of the human body, the skin effectively resists various external stimuli. Once its integrity is compromised, leading to acute or chronic wounds, its protective function is lost. In clinical treatment, wound infections still heavily rely on systemic antibiotic administration. However, the unique environment of chronic wounds and the overuse of antibiotics easily promote the formation of biofilms and the growth of drug-resistant bacteria at the wound site. Although antibiotics play an irreplaceable role in clinically necessary scenarios such as sepsis and transplantation surgery, controlling their usage and developing new strategies to circumvent drug resistance mechanisms have become critical issues that urgently need to be addressed in the field of wound care.

[0003] Traditional local drug delivery systems (such as hydrogels, nanofibers, and liposomes) deliver drugs directly to the wound site, reducing antibiotic resistance to some extent and providing a feasible solution for infection control. Among them, drug delivery systems that can respond to external stimuli to trigger drug release further improve drug delivery conditions and are widely used in the treatment of infected wounds.

[0004] Photothermal therapy, with its advantages of being non-invasive, allowing for high-precision spatiotemporal control, and selectively killing diseased tissues, exhibits antibiotic-free characteristics, opening up a new pathway for addressing drug-resistant bacterial infections, especially suitable for biofilm infections. High temperatures can disrupt the three-dimensional structure of the extracellular polysaccharide matrix, synergistically enhancing the killing effect on deep bacteria, showing great potential in the field of antibacterial therapy. However, the clinical application of traditional photothermal therapy faces two key problems: First, the performance of photothermal conversion materials has stringent requirements for structural design (such as particle size, surface charge, and light absorption peak matching), and is easily affected by physiological environments (such as protein crown formation and tissue scattering), leading to poor treatment repeatability. For example, the SPR peak of gold nanorods needs to be precisely matched with commonly used lasers (808nm or 980nm), and even small size deviations can significantly reduce thermal conversion efficiency; second, prolonged light exposure (usually >5min) and uncontrolled heat diffusion can easily cause thermal damage. High temperatures can not only damage diseased tissues but may also damage the DNA of surrounding healthy cells or induce vascular endothelial damage, increasing the risk of scar formation. In addition, when some photosensitizers (such as ICG) are delivered via liposome encapsulation, their bilayer membrane structure is easily cleared by macrophages in the bloodstream, leading to insufficient local drug accumulation or sudden release, which exacerbates systemic toxicity.

[0005] Chinese invention patent CN115501382B discloses a sustained-release hydrogel wound dressing and its preparation method. Although the sustained-release hydrogel wound dressing proposed in this patent is composed of hydrogel, halloysite nanotubes, phase change materials, drugs and organic photosensitizers, it has excellent biocompatibility, can provide a moist environment for wound healing, and can release drugs under light to accelerate wound healing. However, the dressing has the problem of poor photothermal stability. During the photothermal cycle, the photosensitizer will leak, which will lead to the inability to effectively control the subsequent drug release. Summary of the Invention

[0006] The present invention aims to provide a temperature-self-limiting, controllable drug release photothermal hydrogel membrane and its preparation method, in order to solve the technical problems of poor photothermal stability of hydrogel dressings with added photosensitizers in the prior art, leakage of photosensitizers during photothermal cycling, and uncontrollable subsequent release.

[0007] To solve the above technical problems, the specific solution adopted by the present invention is as follows: a method for preparing a temperature-self-limiting, controllable drug release photothermal hydrothermal gel membrane, comprising the following steps:

[0008] S1. Phase change materials and drugs are co-encapsulated in three-dimensional ordered macroporous carbon to obtain OMCP;

[0009] S2. OMCP was modified with dopamine-like substances to obtain OMCPA;

[0010] S3. Mix OMCPA with acrylamide, crosslinking agent and initiator, add accelerator, and carry out crosslinking polymerization reaction under ice water bath to obtain the temperature self-limiting controllable drug release photothermal gel membrane.

[0011] As a further optimization of the above technical solution, step S1 is as follows: dissolve the phase change material and the drug in an organic solvent to obtain solution A; then dissolve the three-dimensional ordered macroporous carbon in an organic solvent to obtain solution B; mix solution A and solution B and then vacuum at 45°C. After the vacuum is removed, perform an ice-water bath to separate the solid and freeze-dry it to obtain OMCP.

[0012] As a further optimization of the above technical solution, in step S1, the phase change material is a mixture of lauric acid and stearic acid, and the mass ratio of lauric acid to stearic acid is 3.5:1-4:1.

[0013] As a further optimization of the above technical solution, in step S1, the three-dimensional ordered macroporous carbon is obtained by calcining ZIF-8 in an inert atmosphere.

[0014] As a further optimization of the above technical solution, in step S2, the dopamine substance is dopamine hydrochloride, polydopamine, or dopamine powder.

[0015] As a further optimization of the above technical solution, in step S3, OMCPA is modified with dopamine and then mixed with acrylamide, crosslinking agent and initiator.

[0016] As a further optimization of the above technical solution, step S3 is as follows: dissolve DA powder in Tris buffer to obtain PDA chain solution, then mix OMCPA into PDA chain solution, and then add acrylamide, crosslinking agent, initiator and accelerator. Perform crosslinking polymerization reaction under ice water bath to obtain the temperature self-limiting controllable drug release photothermal hydrogel membrane.

[0017] As a further optimization of the above technical solution, in step S3, the crosslinking agent is N,N'-methylenebisacrylamide or polyethylene glycol diacrylate, the initiator is ammonium persulfate or potassium persulfate, and the accelerator is tetramethylethylenediamine.

[0018] As a further optimization of the above technical solution, the ratio of OMCPA to acrylamide is 13:1000-18:1000; the mass ratio of acrylamide to ammonium persulfate is 5:1-10:1; the mass ratio of acrylamide to N,N'-methylenebisacrylamide is 300:1-500:1; and the mass ratio of acrylamide to DA is 150:1-400:1.

[0019] The temperature-controlled drug-releasing photothermal gel membrane prepared by the above method is an example of a temperature-limited, controllable drug-releasing photothermal gel membrane.

[0020] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0021] The three-dimensional ordered macroporous carbon used in this invention achieves significantly improved photothermal stability without leakage risk due to its unique structural characteristics. Its three-dimensional ordered macroporous structure not only provides stable skeletal support, but also, as a photothermal material, it does not rely on the chemical structural stability of traditional photosensitizers to maintain photothermal performance. This avoids the problem of decreased photothermal stability caused by chemical degradation or structural damage of photosensitizer molecules during photothermal cycling. Furthermore, the three-dimensional ordered macroporous carbon itself acts as both a carrier and a photothermal material, eliminating the need for additional photosensitizers and enabling controlled drug release: under light irradiation, the temperature rises, the phase change material melts, and the encapsulated drug is released; when the light irradiation is removed, the temperature drops below the melting point of the phase change material, the phase change material solidifies, and drug release is interrupted, thus achieving a controllable release.

[0022] This invention utilizes a fatty acid eutectic mixture as a phase change material, co-encapsulating it with a drug within an OMC obtained by ZIF-8 carbonization. A DA modification is then used to construct a drug release platform responsive to sunlight. The resulting OMCPA is then doped with an acrylamide solution, and a polydopamine chain solution is added. This is followed by BIS crosslinking and ice-water bath gelation to form a gel. This process achieves multiple beneficial effects: DA modification not only leverages the numerous hydrophilic groups (phenolic hydroxyl and amino groups) in the polydopamine molecule to form strong hydrogen bonds with water molecules, breaking the hydrophobic properties of the three-dimensional ordered macroporous carbon, significantly improving the hydrophilicity and dispersibility of OMCPA and enhancing its photothermal properties, but also effectively limits the loss of phase change material. Simultaneously, during hydrogel preparation, OMCPA forms chemical bonds with the PAM chains rather than simple physical embedding. Furthermore, the macroporous carbon-modified PDA chains are connected to the PAM network through the interaction of catechol groups and PAM amino groups, ensuring uniform dispersion within the hydrogel network. This avoids problems such as material inhomogeneity and loading leakage that may result from physical embedding, ensuring greater material stability during long-term repeated use.

[0023] In this invention, by controlling the mass ratio of lauric acid to stearic acid to be 3.5:1-4:1, the photothermal temperature of the prepared hydrogel film is consistently maintained above 42°C and stable above the melting point of the fatty acid eutectic mixture. This ensures effective heat-triggered drug release while avoiding thermal damage to the surrounding tissues due to excessive temperature. Simultaneously, the combined photothermal and sustained-release treatment effectively prevents bacterial resistance, achieving precise and safe control of drug release. Attached Figure Description

[0024] Figure 1 Scanning electron microscope (SEM) and transmission electron microscope (TEM) images of OMC / OMCP;

[0025] Figure 2 The changes in photothermal properties before and after DA modification;

[0026] Figure 3 The change in dispersion before and after DA modification;

[0027] Figure 4 Simulation of drug release from photothermal hydrogel membranes;

[0028] Figure 5 The photothermal properties of the photothermal hydrogel membrane;

[0029] Figure 6 To improve the photothermal stability of the photothermal hydrogel membrane;

[0030] Figure 7 This describes the drug release behavior of a photothermal hydrogel membrane. Detailed Implementation

[0031] The technical solution of the present invention will be further described in detail below with reference to specific embodiments. Parts not described or disclosed in detail in the following embodiments of the present invention should be understood as prior art known or should be known by those skilled in the art.

[0032] This invention discloses a method for preparing a temperature-self-limiting, controllable drug release photothermal gel membrane, comprising the following steps:

[0033] S1. Phase change materials and drugs are co-encapsulated in three-dimensional ordered macroporous carbon to obtain OMCP;

[0034] Preparation of S101, three-dimensional ordered macroporous carbon (OMC)

[0035] S1011. Dissolve 8-8.5 g Zn(NO3)2 and 6.5-7 g dimethylimidazole in 20-25 ml of methanol respectively, and mix them to obtain a precursor solution. Immerse a polystyrene (PS) template in the precursor solution, vacuum for 15-20 min, and then dry the PS precursor at 60 °C for one day. Afterward, soak the PS@precursor in a mixed solution of methanol and ammonia for 12-15 h in a water bath, and then dry it at 60 °C for 12-15 h (the product is denoted as @PS). The volume ratio of methanol to ammonia is 1:1-1:4. Finally, soak the dried @PS in DMF to remove the PS template. After soaking, centrifuge (2500-3000 rpm, 5-10 min, n=3-5), collect the precipitate, wash with a sufficient amount of dichloromethane to obtain a crystalline composite material, and then dry it to obtain ZIF-8.

[0036] S1012. ZIF-8 was calcined at 800°C for 6 hours under a nitrogen atmosphere to obtain OMC.

[0037] Preparation of S102 and OMCP

[0038] S1021. Dissolve lauric acid and stearic acid in 10-20 ml of methanol to obtain solution A; wherein the mass ratio of lauric acid to stearic acid is 3.5:1-4:1.

[0039] S1022. Dissolve 100-160 mg OMC in 5-10 ml methanol and sonicate for 10-20 min to obtain solution B;

[0040] S1023. Mix solution A and solution B, transfer the mixture to a vacuum apparatus, and evacuate at 45°C for 30-60 minutes. Repeat the loading process three times to improve loading efficiency. After vacuuming, remove the OMC from the ice-water bath for 5-10 minutes. The ice-water bath causes fatty acids to solidify, leaving the drug in the pores of the OMC. Wash the drug-loaded OMC three times with deionized water to remove excess drug, and then freeze-dry to obtain OMCP.

[0041] S2. OMCP was modified with dopamine-like substances to obtain OMCPA.

[0042] Dopamine-like substances include dopamine hydrochloride, polydopamine, or dopamine powder.

[0043] When the dopamine substance is dopamine hydrochloride, step S2 is as follows:

[0044] Dissolve 100-200 mg of dopamine hydrochloride in 5-10 ml of Tris buffer, then add 50-100 mg of OMCP, sonicate for 5-10 min, then shake at 25 °C for 3-6 h, then centrifuge the mixture at 6000 rpm for 10 min, wash with deionized water, and freeze dry. The obtained product is denoted as OMCPA.

[0045] S3. Mix OMCPA with acrylamide, crosslinking agent, and initiator, add accelerator, and carry out crosslinking polymerization reaction under ice-water bath to obtain the temperature-self-limiting controllable drug release photothermal gel membrane (hereinafter referred to as photothermal gel membrane). The ratio of OMCPA to acrylamide added is 13:1000-18:1000.

[0046] The crosslinking agent is N,N'-methylenebisacrylamide or polyethylene glycol diacrylate, the initiator is ammonium persulfate or potassium persulfate, and the accelerator is tetramethylethylenediamine.

[0047] To provide OMCPA with more free catechol groups for sufficient chemical bonding during subsequent hydrogel formation, OMCPA was first modified with dopamine and then mixed with acrylamide, a crosslinking agent, and an initiator.

[0048] Specifically, firstly, DA powder is dissolved in Tris buffer (pH = 8-929), and then self-polymerized in the dark under air atmosphere for 15-20 minutes to obtain a PDA chain solution. Then, OMCPA powder is mixed into the PDA chain solution and sonicated for 1-5 minutes to obtain a PDA-OMCPA solution.

[0049] Acrylamide (AM), N,N'-methylenebisacrylamide (BIS), and ammonium persulfate (APS) were mixed with the above PDA-OMCPA solution and stirred in an ice-water bath. Then, 20-40 μl of tetramethylethylenediamine (TMEDA) was added dropwise. After stirring for 5-10 min, the ice-water bath was removed, and crosslinking polymerization was carried out at room temperature to form a composite hydrogel. The mixture was washed several times with deionized water to remove excess reactants, yielding the photothermal hydrogel membrane.

[0050] The mass ratio of acrylamide to ammonium persulfate is 10:1-15:1; the mass ratio of acrylamide to N,N'-methylenebisacrylamide is 300:1-500:1; and the mass ratio of acrylamide to DA is 150:1-400:1.

[0051] Example 1

[0052] A method for preparing a temperature-self-limiting, controllable drug release photothermal gel membrane includes the following steps:

[0053] S1. Phase change materials and drugs are co-encapsulated in three-dimensional ordered macroporous carbon to obtain OMCP;

[0054] S1011. First, dissolve 8.15g Zn(NO3)2 and 6.75g dimethylimidazole in 25mL and 20mL methanol respectively, and mix them to obtain a precursor solution. Place a certain amount of dried PS template in the above precursor solution and let it stand for 1 hour, then vacuum for 15 minutes to fill the template wells with the precursor solution (denoted as PS@precursor). Subsequently, dry the PS precursor at 60°C for 12 hours to remove methanol. Then, soak the PS@precursor in a 1:1 methanol and ammonia solution. Then, place it under vacuum for 5 minutes, followed by crystallization in a 25°C water bath for 12 hours to allow crystals to grow in the template wells, and then dry it at 60°C for 12 hours (the product is denoted as @PS). Finally, soak the dried @PS in DMF to remove the PS template, changing the DMF every 6 hours for 3 days. After soaking, centrifuge (2500 rpm, 5 min, n=3), collect the precipitate, wash the obtained crystalline composite material with a sufficient amount of dichloromethane, and then dry to obtain ZIF-8.

[0055] S1012. ZIF-8 was calcined at high temperature (800℃) in a nitrogen atmosphere for 6 hours to obtain OMC.

[0056] Preparation of S102 and OMCP

[0057] Dissolve 256 mg of lauric acid, 64 mg of stearic acid, and 12 mg of vancomycin in 10 ml of water and stir well to obtain solution A.

[0058] Dissolve 160 mg of OMC in 5 ml of methanol and sonicate for 5 min to obtain solution B.

[0059] Solution A and solution B were mixed, and the mixture was transferred to a vacuum apparatus. Vacuum was applied at 45°C for 30 minutes, maintaining the vacuum level below -0.05 MPa. After 30 minutes of vacuum treatment, a small amount of methanol was added, and vacuum treatment continued until the methanol was evaporated. This loading process was repeated three times. After vacuum treatment, the mixture was removed and placed in an ice-water bath for 1 minute. Excess drug was removed by washing three times with deionized water, and then freeze-dried to obtain the drug-loaded OMC, denoted as OMCP.

[0060] S2. Modify OMCP to obtain OMCPA.

[0061] Dissolve 200 mg of dopamine hydrochloride in 10 ml of Tris buffer, add 100 mg of OMCP, sonicate for 1 min, then shake at 25 °C for 3 h, then centrifuge the mixture at 6000 rpm for 10 min, wash with deionized water, and freeze dry to obtain the product OMCPA.

[0062] S3. Preparation of photothermal hydrogel membrane.

[0063] First, 5 mg of DA powder was dissolved in 2 ml of Tris buffer (pH = 8.5), and the mixture was shaken in air under dark conditions for 20 min to obtain a PDA chain solution. Then, 220 mg of OMCPA powder was mixed into the PDA chain solution and sonicated for 1 min to obtain a PDA-OMCPA solution.

[0064] 1.5 g AM, 5 mg BIS, and 125 mg APS were mixed with the above PDA-OMCPA solution, 3 ml of water was added, and the mixture was stirred in an ice-water bath. Then, 20 μl of TMEDA was added dropwise. After stirring for 5 min, the ice-water bath was removed, and the mixture was cross-linked and polymerized in a circular template (10 mm in diameter and 1 mm in thickness) to form a composite hydrogel. The mixture was washed several times with deionized water to remove excess reactants, yielding a photothermal hydrogel membrane.

[0065] Example 2

[0066] The overall steps in this embodiment are the same as in Embodiment 1, except that in this embodiment:

[0067] The amount of lauric acid added is 224 mg, the amount of stearic acid added is 64 mg, and the mass ratio of lauric acid to stearic acid is 3.5:1.

[0068] Example 3

[0069] This embodiment is the same as steps S1 and S2 in embodiment 1, except that step S3 in this embodiment is as follows:

[0070] First, 5 mg of DA powder was dissolved in 2 ml of Tris buffer (pH = 8.5), and the mixture was shaken and self-polymerized in air for 20 min under dark conditions to obtain a PDA chain solution. Then, 195 mg of OMCPA powder was mixed into the PDA chain solution and sonicated for 1 min to obtain a PDA-OMCPA solution.

[0071] 1.5 g AM, 5 mg BIS, and 125 mg APS were mixed with the above PDA-OMCPA solution, 3 ml of water was added, and the mixture was stirred in an ice-water bath. Then, 20 μl of TMEDA was added dropwise. After stirring for 5 min, the ice-water bath was removed, and the mixture was cross-linked and polymerized in a circular template (10 mm in diameter and 1 mm in thickness) to form a composite hydrogel. The mixture was washed several times with deionized water to remove excess reactants, yielding a photothermal hydrogel membrane.

[0072] Comparative Examples 1-4

[0073] The difference between this comparative example and Example 1 is the amount of OMCPA added.

[0074] Comparative Example 1: No OMCPA added, i.e., OMCPA content is 0.

[0075] Comparative Example 2: The amount of OMCPA added was adjusted to make the content of OMCPA in the hydrogel 5 wt.%.

[0076] Comparative Example 3: The amount of OMCPA added was adjusted so that the content of OMCPA in the hydrogel was 10 wt.%.

[0077] Comparative Example 4: The amount of OMCPA added was adjusted so that the content of OMCPA in the hydrogel was 20 wt.%.

[0078] The performance of the intermediate products OMC and OMCP prepared in Example 1 and Comparative Examples 1-4, as well as the prepared photothermal hydrothermal gel membranes, was then tested:

[0079] <Scanning electron microscope and transmission electron microscope images>

[0080] Figure 1 The images shown are scanning electron microscope (SEM) and transmission electron microscope (TEM) images of the intermediate products OMC and OMCP prepared in Example 1.

[0081] Photothermal Properties of Photothermal Gel Membranes

[0082] The photothermal gel membrane sample prepared in Example 1 was immersed in 200 μL of deionized water and subjected to sunlight (1 kW / m²). 2 The wound was irradiated for 8 minutes, mimicking a semi-moist environment. Temperature and corresponding thermal images were recorded.

[0083] Meanwhile, the content of OMCPA in the hydrogel in Example 1 was 15 wt.%. To verify the photothermal stability of the photo-thermal hydrogel film prepared in Example 1, the photo-thermal hydrogel films prepared in Example 1 and Comparative Examples 1-4 were respectively placed in the wells of a 48-well plate containing 200 μL of deionized water, and irradiated under one sun (1 kW / m 2 ) to record their temperature changes and corresponding thermal images.

[0084] Result analysis: As Figure 5 shown, as the content of OMCPA increased, the temperature of the photo-thermal hydrogel film increased. The temperatures of the hydrogels containing 10, 15, and 20 wt.% OMCPA reached 40.6, 44.2, and 50.6 °C respectively. The final temperature of the hydrogel containing 10 wt.% OMCPA was 40.6 °C, lower than the melting temperature of the PCM, and the drug could not be released under sunlight irradiation. When the OMCPA content was 20 wt.%, the hydrogel could reach 45 °C within 2 min, with too fast temperature increase. The final temperature of the hydrogel containing 15 wt.% OMCPA was 44.6 °C, which was sufficient to completely melt the PCM and release the payload from OMC. More importantly, the temperature of the hydrogel at this content reached an equilibrium state of 44 °C within 4 min, which effectively prevented the skin from being scalded.

[0085] <Changes in photothermal properties before and after DA modification>

[0086] First, 1 mL of the OMCP suspension (50 mg / ml) before and after modification was respectively introduced into the wells of a 48-well plate. Subsequently, the above suspension was irradiated under one sun (1 kW / m2) for 8 minutes. With the help of a handheld infrared thermal imager, the temperature changes and corresponding thermal images were recorded.

[0087] As Figure 2 shown, under the irradiation of one sun (1 kW / m 2 ), compared with the temperature change curve of the original OMCP, the final temperature of OMCPA after DA modification increased by about 2 °C, indicating that the modification of DA promoted the photothermal effect of OMCP.

[0088] <Changes in dispersibility before and after DA modification>

[0089] As Figure 3 shown by the infrared spectrum, in the spectrum of OMCPA, the two peaks between 1250 and 1520 cm -1 came from the bending and stretching vibrations of phenolic C-OH; the peak appearing around 1462 cm -1 was the N-H shear vibration of the amide group. The above results all indicated the successful modification of DA. Compared with OMCP, the dispersibility of OMCPA after DA modification in water was significantly improved.

[0090] Photothermal stability of photothermal gel membranes

[0091] To ensure that the PCM can melt and release the drug during long-term cyclic use, and to prevent skin burns, the photothermal hydrogel membrane was subjected to cyclic light irradiation, and the temperature changes of the photothermal hydrogel membrane were observed.

[0092] like Figure 6 As shown, in 24 rounds of "on-off" experiments, the temperature change of the photothermal hydrogel membrane showed similar curves, with the temperature stabilizing at around 44℃, remaining above the melting point of PCM, and preventing thermal damage to the wound skin tissue caused by excessive temperature.

[0093] Controlled drug release from photothermal hydrogel membranes

[0094] Four parallel photothermal hydrogel membranes were placed in the wells of a 48-well plate containing 200 μL of deionized water. The plate was then irradiated with a solar simulator, and the temperature was monitored and maintained above 42°C for 5 min. The irradiated liquid was collected and analyzed using a UV-Vis spectrophotometer. Then, 200 μL of deionized water was added to the irradiated hydrogel, and the plate was incubated at room temperature for 5 min. The supernatant was collected and analyzed using a UV-Vis spectrophotometer. The photothermal hydrogel membranes were placed under sunlight (1 kW / m²). 2 The gel was repeatedly irradiated until vancomycin was no longer detectable in the supernatant of the hydrogel after irradiation.

[0095] Results analysis: Drug release was maintained for 6 rounds, from... Figure 7 It can be seen that the drug release is triggered by light irradiation, with minimal release upon interruption of light exposure. After the first round of light irradiation, a vancomycin concentration of 7.4 μg / mL was detected, sufficient to inhibit the proliferation of Staphylococcus aureus. After 2, 3, 4, 5, and 6 rounds of light irradiation, the cumulative drug concentrations released were 14.6, 24.2, 36, 46.8, and 56.6 μg / mL, respectively. Therefore, under light irradiation, the drug can be released from the hydrogel, which is difficult to achieve with other drug delivery systems based on diffusion or matrix degradation.

[0096] <Controlled Release from Photothermal Gel Membrane>

[0097] 256 mg lauric acid, 64 mg stearic acid, 160 mg OMC, and 120 mg rhodamine B were dissolved in 20 ml methanol and sonicated for 5 min. The solution was then transferred to a vacuum apparatus and vacuum-treated at 45 °C for 1 h. After vacuum treatment, the solution was removed and placed in an ice-water bath for 1 min to obtain CPBA. DA powder was then dissolved in Tris buffer (pH 8.5), and the mixture was aerobically shaken in the dark for 30 min to obtain PDA solution. CPBA, AM, BIS, APS, and TMEDA were then mixed into the PDA solution and stirred in an ice-water bath to form a gel. The resulting hydrogel was then placed into the wells of a 48-well plate, 400 μL of deionized water was added, and the plate was then irradiated with sunlight and kept stable. The changes in the area covered by rhodamine B in the hydrogel and surrounding environment under illumination over time were observed using a fluorescence inverted microscope.

[0098] Results analysis: Figure 4 Fluorescence imaging showed that local fluorescence was present on the surface of the hydrogel before irradiation. After irradiation, when the temperature reached above the melting point of PCM, the model drug Rhodamine B began to be released. With the continuous release of Rhodamine B, the fluorescent area gradually increased and the fluorescence intensity gradually increased.

[0099] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a temperature-self-limiting, controllable drug release photothermal gel membrane, characterized in that, Includes the following steps: S1. Phase change materials and drugs are co-encapsulated in three-dimensional ordered macroporous carbon to obtain OMCP; S2. OMCP was modified with dopamine-like substances to obtain OMCPA; S3. Mix OMCPA with acrylamide, crosslinking agent and initiator, add accelerator, and carry out crosslinking polymerization reaction under ice water bath to obtain the temperature self-limiting controllable drug release photothermal gel membrane.

2. The method for preparing a temperature-self-limiting, controllable drug release photothermal gel membrane according to claim 1, characterized in that, Step S1 specifically involves: dissolving the phase change material and the drug in an organic solvent to obtain solution A; then dissolving the three-dimensional ordered macroporous carbon in an organic solvent to obtain solution B; mixing solutions A and B and then evacuating them at 45°C; after the vacuum is removed, performing an ice-water bath to separate the solids and freeze-drying them to obtain OMCP.

3. The method for preparing a temperature-self-limiting, controllable drug-release photothermal gel membrane according to claim 1, characterized in that, In step S1, the phase change material is a mixture of lauric acid and stearic acid, with a mass ratio of lauric acid to stearic acid of 3.5:1-4:

1.

4. The method for preparing a temperature-self-limiting, controllable drug release photothermal gel membrane according to claim 1, characterized in that, In step S1, the three-dimensional ordered macroporous carbon is prepared by calcining ZIF-8 in an inert atmosphere.

5. The method for preparing a temperature-self-limiting, controllable drug release photothermal gel membrane according to claim 1, characterized in that, In step S2, the dopamine-like substance is dopamine hydrochloride, polydopamine, or dopamine powder.

6. The method for preparing a temperature-self-limiting, controllable drug release photothermal gel membrane according to claim 1, characterized in that, In step S3, OMCPA is further modified with dopamine and then mixed with acrylamide, crosslinking agent, and initiator.

7. The method for preparing a temperature-self-limiting, controllable drug-release photothermal gel membrane according to claim 6, characterized in that, Step S3 specifically involves dissolving DA powder in Tris buffer to obtain a PDA chain solution, then mixing OMCPA into the PDA chain solution, and adding acrylamide, crosslinking agent, initiator, and accelerator. The crosslinking polymerization reaction is carried out under an ice-water bath to obtain the photothermal hydrogel membrane.

8. The method for preparing a temperature-self-limiting, controllable drug release photothermal gel membrane according to claim 7, characterized in that, In step S3, the crosslinking agent is N,N'-methylenebisacrylamide or polyethylene glycol diacrylate, the initiator is ammonium persulfate or potassium persulfate, and the accelerator is tetramethylethylenediamine.

9. The method for preparing a temperature-self-limiting, controllable drug-release photothermal gel membrane according to claim 8, characterized in that, The ratio of OMCPA to acrylamide is 13:1000-18:1000; the mass ratio of acrylamide to ammonium persulfate is 10:1-15:1; the mass ratio of acrylamide to N,N'-methylenebisacrylamide is 300:1-500:1; and the mass ratio of acrylamide to DA is 150:1-400:

1.

10. A temperature-self-limiting, controllable drug-releasing photothermal gel membrane prepared by the preparation method according to any one of claims 1-9.

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