A preparation method of a ternary visible light response type controllable drug release material based on double-layer titanium dioxide nanotube array

Abstract

The application discloses a preparation method of a ternary visible light response type controllable drug release material based on a double-layer titanium dioxide nanotube array. The steps are as follows: taking glycerol as an electrolyte component, adopting an anodic oxidation method to obtain a titanium dioxide nanotube array, performing silver nanoparticle modification, and calcining; then, sequentially immersing into a bismuth nitrate solution and a sodium sulfide solution to perform bismuth sulfide quantum dot sensitization, obtaining a composite titanium dioxide nanotube array as an anode, taking ethylene glycol as an electrolyte component, performing secondary anodic oxidation, and calcining; immersing into a GPMS toluene solution for pretreatment, then immersing into an amoxicillin solution to perform template drug loading; finally, immersing into a HDTMS methanol solution and adjusting a pH value to 3-6, thereby obtaining the product. The application constructs a double-layer titanium dioxide nanotube array as a light response layer and a drug loading layer respectively, so that exogenous light response controllable drug release at an infection site is realized, the disadvantages of systemic administration are avoided, and a local anti-infection treatment effect is achieved.

Description

Technical Field

[0001] This invention belongs to the field of photocatalytic synthesis materials technology, specifically relating to a method for preparing a ternary visible light responsive controlled-release drug material based on a double-layer titanium dioxide nanotube array. Background Technology

[0002] Controlled drug delivery technology, by enabling the targeted release of active substances at the correct time and place, effectively avoids the drawbacks of systemic drug delivery and solves problems such as low bioavailability. Many potential drug carriers have been discovered, including gels, micelles, nanoparticles, and nanotubes. Among them, nanotube-based drug carriers have attracted much attention due to their inherent high specific surface area and stable geometry. However, the triggering of drug release is related to surrounding environmental factors, such as pH, temperature, and light source, which imposes many limitations in practical applications.

[0003] Over the past decade, porous titanium dioxide nanotube arrays prepared by electrochemistry have become a promising candidate for drug delivery due to their unique tubular structure and the presence of titanium hydroxyl groups on the nanotube walls, enabling them to carry active molecules and exhibiting good biocompatibility. Furthermore, the inherent photocatalytic activity of titanium dioxide allows it to respond to external light sources, enabling the construction of photoresponsive drug delivery platforms. However, the large band gap (3.0 eV–3.2 eV) of titanium dioxide limits its photoactivity to ultraviolet light triggering. Ultraviolet light has limited tissue penetration and can cause irreversible photodamage to normal cells, thus restricting its application in drug delivery. Summary of the Invention

[0004] To address the aforementioned issues, this invention provides a method for preparing a ternary visible light-responsive controlled-release drug material based on a bilayer titanium dioxide nanotube array. The bilayer titanium dioxide nanotube array is constructed as both the photoresponsive layer and the drug-carrying layer, achieving visible light response and controlled drug release. This enables exogenous photoresponsive controlled-release of drugs at the site of infection, avoiding the drawbacks of systemic administration and achieving a local anti-infective therapeutic effect.

[0005] To achieve the above-mentioned technical objectives, the present invention adopts the following technical solution:

[0006] This invention provides a method for preparing a ternary visible light-responsive controlled-release drug material based on a double-layer titanium dioxide nanotube array, specifically including the following steps:

[0007] 1) An amorphous titanium dioxide nanotube array was obtained on the surface of a titanium sheet by anodizing; the electrolyte solution was a mixed solution of ammonium fluoride, water and glycerol.

[0008] 2) The amorphous titanium dioxide nanotube array obtained in step 1) is modified with silver nanoparticles using the silver ammonia method, and then calcined to obtain a titanium dioxide nanotube array modified with silver nanoparticles.

[0009] 3) The silver nanoparticle-modified titanium dioxide nanotube array obtained in step 2) is sequentially immersed in bismuth nitrate solution and sodium sulfide solution for bismuth sulfide quantum dot sensitization to obtain a composite titanium dioxide nanotube array.

[0010] 4) Using the composite titanium dioxide nanotube array obtained in step 3) as the anode, perform secondary anodizing and then calcination to obtain a new layer of titanium dioxide nanotube array; wherein the electrolyte solution is a mixed solution composed of ammonium fluoride, water and ethylene glycol;

[0011] 5) The sample obtained in step 4) was pretreated by immersing it in a γ-glycidyl oxypropyltrimethoxysilane (GPMS) toluene solution, and then immersed in an amoxicillin solution for template drug loading, loading amoxicillin into the newly obtained titanium dioxide nanotube array in step 4).

[0012] 6) Immerse the sample obtained in step 5) in a hexadecyltrimethoxysilane (HDTMS) methanol solution and adjust the pH value to 3-6 to obtain a ternary visible light responsive controlled-release drug material based on titanium dioxide nanotube array.

[0013] According to the above scheme, in step 1), the ammonium fluoride content in the electrolyte solution is 0.5-2.0 wt% by mass percentage, and the volume ratio of water to glycerol is 1:1-3.

[0014] According to the above scheme, in step 1), in the anodic oxidation method, a graphite electrode is used as the cathode, a titanium sheet is used as the anode, an external DC voltage of 10-80V is applied, and the anodic oxidation is carried out for 1-10 hours.

[0015] According to the above scheme, in step 2), the specific steps of the silver ammonia method are as follows: add ammonia solution to silver nitrate solution until it becomes clear, then add polyvinylpyrrolidone (PVP), immerse the titanium dioxide nanotube array prepared in step 1) in it for 1 to 10 minutes, wash away excess silver ions, and then immerse it in glucose solution for 1 to 10 minutes to obtain the titanium dioxide nanotube array modified with silver nanoparticles.

[0016] Preferably, the concentration of silver nitrate solution is 10–100 mmol / L, the concentration of ammonia solution is 0.1–10 mol / L, the mass ratio of silver nitrate to PVP is 1:1–5, and the concentration of glucose solution is 1–50 mmol / L.

[0017] Preferably, the temperature of the glucose solution is 20–100°C.

[0018] According to the above scheme, in step 2), the calcination temperature is 200-500℃ and the calcination time is 1-8h; preferably, the heating rate is 2-10℃ / min.

[0019] According to the above scheme, in step 3), the solvents for the bismuth nitrate solution and the sodium sulfide solution are a mixed solution of glycerol, methanol and water; wherein, by volume percentage, glycerol is 1-30%, and the volume ratio of water to methanol is 1:1-5.

[0020] According to the above scheme, in step 3), the concentration of bismuth nitrate solution is 0.01-0.10 mol / L, and the concentration of sodium sulfide solution is 0.01-0.10 mol / L.

[0021] According to the above scheme, in step 3), the immersion time of the titanium dioxide nanotube array in the bismuth nitrate solution is 1-20 min; the immersion time in the sodium sulfide solution is 1-20 min.

[0022] According to the above scheme, in step 4), the ammonium fluoride content in the electrolyte solution is 0.2-1.0% by mass percentage, and the water content is 1-10% by volume percentage.

[0023] According to the above scheme, in step 4), the graphite electrode is used as the cathode and the composite titanium dioxide nanotube array obtained in step 3) is used as the anode for anodizing. An external DC voltage of 10-80V is applied and the anodizing time is 10-120min.

[0024] According to the above scheme, in step 4), the calcination temperature is 200-500℃ and the calcination time is 20-120 min; preferably, the heating rate is 2-10℃ / min.

[0025] According to the above scheme, in step 5), the concentration of the γ-glycidoxypropyltrimethoxysilane (GPMS) toluene solution is 1-30 mmol / L.

[0026] According to the above scheme, in step 5), the immersion time of the sample obtained in step 4) in the γ-glycidyl etheroxypropyltrimethoxysilane (GPMS) toluene solution is 2–48 h. Preferably, after immersion, it is rinsed with anhydrous ethanol for 1–30 min and then dried.

[0027] According to the above scheme, in step 5), the concentration of amoxicillin solution is 0.01-0.1 mol / L.

[0028] According to the above scheme, in step 5), the solvent for the amoxicillin solution is a mixture of DMSO and ethanol; preferably, the volume ratio of DMSO to ethanol is 1:1 to 8.

[0029] According to the above scheme, in step 5), the immersion time in 0.01–0.1 mol / L amoxicillin solution is 2–48 h. Preferably, after immersion, the sample is rinsed with DMSO / ethanol solution for 1–30 min and then dried.

[0030] According to the above scheme, in step 6), the concentration of hexadecyltrimethoxysilane in the hexadecyltrimethoxysilane (HDTMS) methanol solution is 0.1-10 wt%.

[0031] According to the above scheme, in step 6), the sample obtained in step 5) is immersed in a hexadecyltrimethoxysilane (HDTMS) methanol solution for 2 to 6 minutes, and repeated 1 to 3 times.

[0032] This invention provides a method for preparing a ternary visible light-responsive controlled-release drug material based on a bilayer titanium dioxide nanotube array. The bilayer titanium dioxide nanotube array is constructed as both the photoresponsive layer and the drug-carrying layer. The specific mechanism is as follows:

[0033] First, a composite titanium dioxide nanotube array was constructed as a photoresponse layer. The titanium dioxide nanotube array was then modified with "green and non-toxic" bismuth sulfide quantum dots and silver nanoparticles to broaden its absorption range into the visible light region.

[0034] This invention uses glycerol as the organic electrolyte solution component to prepare amorphous titanium dioxide nanotube arrays via anodic oxidation. Compared to titanium dioxide nanotube arrays prepared using ethylene glycol as the organic electrolyte solution component in traditional methods, these arrays are independently dispersed tubular with complete separation between tubes, resulting in a larger specific surface area, which is more conducive to the loading of silver and bismuth sulfide quantum dots. Furthermore, photogenerated electrons generated under photocatalysis can flow along the thinner tube walls to the surface of the titanium dioxide nanotubes, thereby better promoting the separation of photogenerated charge carriers and improving the photocatalytic performance of the material. This provides a good foundation for further modification work.

[0035] The titanium dioxide nanotube array obtained by the anodic oxidation method of this invention is not calcined immediately, but is first modified with silver nanoparticles and then co-calcined. This is beneficial for fixing the silver nanoparticles on the walls of the titanium dioxide nanotubes, effectively preventing the silver nanoparticles from falling off. During the calcination process, silver can also be embedded inside the titanium dioxide lattice, thereby improving the photoelectric properties of titanium dioxide itself. At the same time, it is easier to load during the subsequent bismuth sulfide quantum dot sensitization, requiring only a small number of loading cycles to obtain better photocatalytic performance, thus saving operating costs.

[0036] Secondly, a drug-carrying layer of titanium dioxide nanotube array is constructed and combined with a photoresponsive layer to achieve controlled drug release at the infection site using exogenous photoresponse.

[0037] This invention utilizes ethylene glycol as the organic electrolyte solution component for secondary anodic oxidation, thereby growing a titanium dioxide nanotube array on the surface of a titanium sheet. The smooth tube walls and tightly packed arrangement of the tubes make them excellent drug carriers. Then, GPMS is used as a "linker" to covalently link the template drug amoxicillin. Compared to physical adsorption, covalent linking effectively anchors the drug to the titanium dioxide nanotube walls, avoiding the instability caused by the free diffusion mechanism of physical adsorption. Finally, a silane coupling agent (HDTMS) is used to hydrophobically "encapsulate" the material surface. By adjusting the appropriate pH, HDTMS can quickly hydrophobically treat the material. The long-chain alkyl groups of HDTMS can isolate the loaded drug from the solvent, preventing pre-release of the drug. This achieves exogenous light-responsive controlled drug release at the infection site, avoiding the drawbacks of systemic administration and achieving a local anti-infective therapeutic effect.

[0038] The beneficial effects of this invention are as follows:

[0039] This invention provides a method for preparing a ternary visible-light-responsive controlled-release drug material based on a bilayer titanium dioxide nanotube array. A visible-light-responsive bilayer drug-release platform (upper photoresponsive layer and lower drug-loaded layer) is constructed based on the titanium dioxide nanotube array. The photoresponsive layer aims to overcome the limitation of titanium dioxide's inability to respond to visible light due to its large band gap by using quantum dot sensitization and noble metal deposition. The drug-loaded layer utilizes its highly ordered tubular structure to form a biocompatible framework capable of carrying active molecules, making it possible to load drugs or graft macromolecules. The template drug is covalently linked using hydroxyl groups on the nanotube walls. Finally, the titanium dioxide nanotube array is encapsulated using a silane coupling agent to achieve controlled pre-release. This invention fully utilizes the excellent optical activity of the bilayer drug-release platform and the good biocompatibility of titanium dioxide itself. With the aid of an external visible light source, the drug is released in a controlled manner through external stimulation, achieving a certain drug concentration at the lesion site for effective treatment. Attached Figure Description

[0040] Figure 1 This is a comparison diagram of the electrochemical impedance of the titanium dioxide nanotube arrays obtained in step 1) of Example 1 of the present invention and Comparative Example 1.

[0041] Figure 2 This is a comparison diagram of the electrochemical impedance of the silver-modified titanium dioxide nanotube arrays obtained in step 2 of Example 1 of the present invention and Comparative Example 2.

[0042] Figure 3 This is a comparison chart of the amoxicillin release amounts of the products obtained in Example 1 and Comparative Example 3 of the present invention under visible light.

[0043] Figure 4 This is a comparison chart of the amoxicillin release amounts of the products obtained in Example 1 and Comparative Example 4 of the present invention under visible light.

[0044] Figure 5 This is a comparison chart of the amoxicillin release amounts of the products obtained in Example 1 and Comparative Example 5 of the present invention under visible light.

[0045] Figure 6 This is the XRD pattern of Embodiment 1 of the present invention.

[0046] Figure 7 This is an FESEM image of Embodiment 1 of the present invention.

[0047] Figure 8 The image is a FESEM image of the amorphous titanium dioxide nanotube array prepared by step (1) of Example 1 of the present invention after calcination.

[0048] Figure 9 This is a FESEM image of the titanium dioxide nanotube array prepared in Comparative Example 1 of this invention. Detailed Implementation

[0049] To better understand the present invention, the following embodiments further illustrate the content of the present invention, but the present invention is not limited to the following embodiments and comparative examples.

[0050] Example 1

[0051] A method for preparing a ternary visible-light-responsive controlled-release drug material based on a titanium dioxide nanotube array is provided, specifically including the following steps:

[0052] (1) Fabrication of a single-stage anodized titanium dioxide nanotube array (photoresponsive layer)

[0053] Titanium sheets were pretreated by sanding to remove the oxide layer and stains from their surface. Anodizing was then performed using a graphite electrode as the cathode and the treated titanium sheet as the anode. The electrolyte solution consisted of a mixture of 0.75 wt% ammonium fluoride, 60 wt% glycerol, and 40 wt% water. A DC voltage of 30 V was applied, and anodizing was carried out for 3.5 hours, resulting in an amorphous titanium dioxide nanotube array, denoted here as TNTs-GL.

[0054] (2) Fabrication of silver-modified titanium dioxide nanotube array (photoresponsive layer)

[0055] The titanium dioxide nanotube array obtained in step (1) was modified using the silver ammonia method. A 10 mmol / L silver nitrate solution was prepared and added dropwise with a 1 mol / L ammonia solution until the solution was clear. Polyvinylpyrrolidone K30 (PVP) was then added, with a silver nitrate to PVP mass ratio of 1:1. The titanium dioxide nanotube array prepared in step (1) was immersed in the solution for 5 min, then excess silver ions were washed off with deionized water, and then immersed in a 20 mmol / L glucose solution for 5 min at a temperature of 40 °C. Finally, excess glucose solution was washed off with deionized water, and the array was dried in an oven at 50 °C for 12 h. Then, it was calcined in a muffle furnace at a temperature of 400 °C for 1 h at a heating rate of 2 °C / min. The array was then stored in a dry place for later use. This is referred to as A-TNTs (co-calcined).

[0056] (3) Fabrication of bismuth sulfide quantum dot-sensitized silver-modified titanium dioxide nanotube array (photoresponsive layer)

[0057] The titanium dioxide nanotube array obtained in step (2) was sensitized with bismuth sulfide quantum dots using a continuous ion layer adsorption method: First, the titanium dioxide nanotube array obtained in step (2) was immersed in a 0.05 mol / L bismuth nitrate methanol / water solution (where the volume ratio of methanol to water was 1:1, and a small amount of glycerol was added to promote dissolution, accounting for 5% of the total volume of the solution) for 2 min. Then, excess bismuth ions were washed with the same volume ratio of methanol / water solution. Next, it was immersed in a 0.05 mol / L sodium sulfide methanol / water solution for 2 min, where the ratio of methanol to water was the same as above. Finally, excess sulfide ions were washed with the same volume ratio of methanol / water solution (where the volume ratio of methanol / water solution was 1:1). This process was repeated twice. After washing, the array was placed in an oven at 50°C and dried for 12 h to obtain a composite titanium dioxide nanotube array, which was then designated as AB-TNTs.

[0058] (4) Preparation of secondary anodic oxidation titanium dioxide nanotube array (drug loading layer)

[0059] The anodic oxidation method was adopted, with a graphite electrode as the cathode and the composite titanium dioxide nanotube array prepared in step (3) as the anode. The electrolyte solution was a mixed solution of ethylene glycol containing 0.3 wt% ammonium fluoride and 2 wt% water. A DC voltage of 50 V was applied, and the anodic oxidation was carried out for 20 min to grow a titanium dioxide nanotube array (denoted as L-TNTs). The array was located between the titanium sheet and the composite titanium dioxide nanotube array. Finally, it was placed in a muffle furnace for calcination at a temperature of 250 °C for 20 min with a heating rate of 2 °C / min. The array was then placed in a dry place for later use.

[0060] (5) Template drug loading

[0061] The sample prepared in step (4) was immersed in a 10 mmol / L GPMS toluene solution for 12 h, rinsed with anhydrous ethanol for 5 min, dried, and then immersed in a 0.01 mol / L amoxicillin DMSO / ethanol solution for 48 h, with a volume ratio of DMSO to ethanol of 1:2. It was then rinsed with the above solvent for 5 min and placed in a dry place for later use.

[0062] (6) Packaging materials

[0063] The sample prepared in step (5) was immersed in a 0.35 wt% HDTMS methanol solution, and the pH was adjusted to 3.5. The soaking time was 5 min, and the process was repeated 3 times. After drying, the sample was stored at 2°C. This sample was designated as AB-TNTs / L-TNTs.

[0064] Comparative Example 1

[0065] This comparative example only constructed an unmodified titanium dioxide nanotube array (photoresponsive layer only).

[0066] Fabrication of a single-stage anodized titanium dioxide nanotube array (photoresponsive layer)

[0067] Titanium sheets were pretreated by sanding to remove the oxide layer and stains from their surface. Anodizing was then performed using a graphite electrode as the cathode and the treated titanium sheet as the anode. The electrolyte solution consisted of a mixture of 0.35 wt% ammonium fluoride, 2 wt% water, and ethylene glycol. A DC voltage of 30 V was applied, and anodizing was carried out for 1 hour to prepare a titanium dioxide nanotube array on the titanium sheet surface. The sample was then calcined in a muffle furnace at 400 °C for 1 hour at a heating rate of 2 °C / min. The sample was then stored in a dry place for later use. This sample is designated TNTs-EG.

[0068] Comparative Example 2

[0069] (1) Fabrication of a single-stage anodized titanium dioxide nanotube array (photoresponsive layer)

[0070] Titanium sheets were pretreated by sanding to remove the oxide layer and stains from their surface. Anodizing was then performed using a graphite electrode as the cathode and the treated titanium sheet as the anode. The electrolyte solution consisted of a mixture of 0.75 wt% ammonium fluoride, 60 wt% glycerol, and 40 wt% water. A DC voltage of 30 V was applied, and anodizing was carried out for 3.5 hours to prepare a titanium dioxide nanotube array on the titanium sheet surface. The array was then calcined in a muffle furnace at 400 °C for 1 hour at a heating rate of 2 °C / min, and then stored in a dry place for later use.

[0071] (2) Fabrication of silver-modified titanium dioxide nanotube array (photoresponsive layer)

[0072] The titanium dioxide nanotube array obtained in step (1) was modified using the silver ammonia method. A 10 mmol / L silver nitrate solution was prepared, and 1 mol / L ammonia solution was added dropwise until a clear solution was obtained. PVP was then added, with a silver nitrate to PVP mass ratio of 1:1. The titanium dioxide nanotube array prepared in step (1) was immersed in the solution for 5 min, then excess silver ions were washed off with deionized water, and then immersed in a 20 mmol / L glucose solution for 5 min. The solution was heated to 40 °C, and finally excess glucose solution was washed off with deionized water. The sample was then dried in an oven at 50 °C for 12 h. This sample was designated as A-TNTs (calcined first, then silver coated).

[0073] Comparative Example 3

[0074] This comparative example only constructed a silver-modified titanium dioxide nanotube array bilayer drug controlled release platform.

[0075] (1) Fabrication of a single-stage anodized titanium dioxide nanotube array (photoresponsive layer)

[0076] The preparation method is the same as step (1) in Example 1.

[0077] (2) Fabrication of silver-modified titanium dioxide nanotube array (photoresponsive layer)

[0078] The sample prepared in step (1) was modified with silver nanoparticles according to step (2) in Example 1.

[0079] (3) Preparation of secondary anodic oxidation titanium dioxide nanotube array (drug loading layer)

[0080] The sample prepared in step (2) was subjected to secondary anodizing in step (4) of Example 1.

[0081] (4) Template drug loading

[0082] The sample prepared in step (3) was loaded with drugs according to step (5) in Example 1.

[0083] (5) Packaging materials

[0084] The sample prepared in step (4) was packaged according to step (6) in Example 1. This sample is designated as A-TNTs / L-TNTs.

[0085] Comparative Example 4

[0086] This comparative example only constructed a bilayer drug release platform using bismuth sulfide quantum dot-sensitized titanium dioxide nanotube arrays.

[0087] (1) Fabrication of a single-stage anodized titanium dioxide nanotube array (photoresponsive layer)

[0088] The preparation method is the same as step (1) in Example 1.

[0089] (2) Fabrication of bismuth sulfide quantum dot-sensitized titanium dioxide nanotube array (photoresponsive layer)

[0090] The sample prepared in step (1) was sensitized with bismuth sulfide quantum dots according to step (3) in Example 1.

[0091] (3) Preparation of secondary anodic oxidation titanium dioxide nanotube array (drug loading layer)

[0092] The sample prepared in step (2) was subjected to secondary anodizing in step (4) of Example 1.

[0093] (4) Template drug loading

[0094] The sample prepared in step (3) was loaded with drugs according to step (5) in Example 1.

[0095] (5) Packaging materials

[0096] The sample prepared in step (4) was packaged according to step (6) of Example 1. This sample is designated as B-TNTs / L-TNTs.

[0097] Comparative Example 5

[0098] In this comparative example, the photoresponsive layer was removed, and only the lower titanium dioxide nanotube array (drug-carrying layer only) was constructed.

[0099] (1) Fabrication of anodized titanium dioxide nanotube arrays (drug-carrying layer)

[0100] The preparation method is the same as step (4) in Example 1.

[0101] (2) Template drug loading

[0102] The sample prepared in step (1) was loaded with drug according to step (5) in Example 1. This sample was designated as L-TNTs.

[0103] The controlled drug release performance of the prepared drug release material was monitored.

[0104] The samples prepared according to Example 1 and Comparative Examples 3-5 were immersed in 5 ml of PBS solution (pH = 7.2-7.4), with the liquid surface 25 cm away from the light source. They were first placed in the dark for 30 min, then a 300 W xenon lamp (>420 nm) was turned on. Every 10 min, 20 μl of the solution was taken, filtered through a 0.45 μm filter, and analyzed using high-performance liquid chromatography (HPLC). The stationary phase was a phenyl column, and the mobile phase was anhydrous methanol and 0.05 vt% formic acid solution in a volume ratio of 1:9. The flow rate was adjusted to 1 mL / min. The concentration of the released drug was monitored at different time points. The release performance and material characterization are described in [the table below]. Figures 3 to 5.

[0105] Depend on Figure 1 It is known that the titanium dioxide nanotube array prepared using glycerol (GL) as the organic electrolyte solution has a lower electrochemical impedance than the titanium dioxide nanotube array prepared using ethylene glycol (EG) as the organic electrolyte solution. Therefore, the photogenerated carriers generated under photocatalysis flow more easily, which is beneficial to improving the photocatalytic performance of the material. Figure 2 It is known that the electrochemical impedance of the amorphous titanium dioxide nanotube array prepared by first modifying it with silver nanoparticles and then co-calcining it is significantly reduced compared with the method of first calcining the prepared amorphous titanium dioxide nanotube array and then modifying it with silver nanoparticles. Therefore, co-calcination can effectively fix the silver nanoparticles, further optimize the photoelectric properties of the material, promote the separation of photogenerated electrons and holes, and improve the photocatalytic performance of the material.

[0106] Depend on Figure 3 and Figure 4 It is known that, compared to A-TNTs / L-TNTs and B-TNTs / L-TNTs, AB-TNTs / L-TNTs can reach peak drug release at 50 minutes and release a greater amount of drug, while A-TNTs / L-TNTs and B-TNTs / L-TNTs require 80 minutes. Therefore, AB-TNTs / L-TNTs can release the drug faster and more efficiently under visible light. Figure 5 It can be seen that when the photoresponsive layer is removed (comparative example 5L-TNTs), the drug-loaded layer cannot controllably release the drug under visible light, and the amount of drug released is about 1 / 3 of that of AB-TNTs / L-TNTs. Figure 6 It can be seen that both AB-TNTs / L-TNTs and unmodified TNTs / L-TNTs have diffraction peaks at 25.26°, 37.84°, 48.02°, 53.88°, 55.00°, 62.72°, 73.98°, and 75.02°, corresponding to the (101), (004), (200), (105), (211), (204), (107), and (215) crystal planes on the standard card JCPDS No. 21-1272, respectively. That is, TiO2 in all samples is anatase. Moreover, the XRD pattern of the modified AB-TNTs / L-TNTs does not show any diffraction peak shifts compared to the XRD pattern of the original TNTs / L-TNTs, which indicates that these two sensitization methods do not lead to a change in the anatase crystal form of titanium dioxide.

[0107] In addition, the AB-TNTs / L-TNTs drug release platform was characterized cross-sectionally using FESEM. Figure 7 The visible light-responsive bilayer drug release platform clearly shows an upper photoresponsive layer and a lower drug-loaded layer. Figure 8 It can be seen that the amorphous titanium dioxide nanotube array prepared in step 1) of Example 1 using glycerol as the organic electrolyte solution component, after calcination, exhibits an independent and dispersed state between the tubes, with an inner diameter of approximately 110 nm, and both the inner and outer walls of the tubes are exposed. In contrast, the titanium dioxide nanotube array prepared in Comparative Example 1 using ethylene glycol as the organic electrolyte solution component (…) Figure 9 The tubes are tightly connected, with an inner diameter of about 80-90 nm, and only the inner wall of the tube is exposed. Therefore, compared with the traditional method (using ethylene glycol as an organic electrolyte solution), the titanium dioxide nanotube array prepared with glycerol has a larger contact area with silver nanoparticles and bismuth sulfide quantum dots, which is beneficial to improving the optical activity of titanium dioxide nanotubes and thus improving their photocatalytic performance.

[0108] Obviously, the above embodiments and comparative examples are merely illustrative examples and not intended to limit the implementation. Those skilled in the art will recognize that various variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations. However, obvious variations or modifications derived therefrom remain within the scope of this invention.

Claims

1. A method for preparing a ternary visible-light-responsive controlled-release drug material based on a double-layer titanium dioxide nanotube array, characterized in that, Specifically, the following steps are included: 1) An amorphous titanium dioxide nanotube array was obtained on the surface of a titanium sheet by anodizing. The electrolyte solution is a mixed solution composed of ammonium fluoride, water and glycerol; 2) The amorphous titanium dioxide nanotube array obtained in step 1) is modified with silver nanoparticles using the silver ammonia method, and then calcined to obtain a titanium dioxide nanotube array modified with silver nanoparticles. 3) The silver nanoparticle-modified titanium dioxide nanotube array obtained in step 2) is sequentially immersed in bismuth nitrate solution and sodium sulfide solution for bismuth sulfide quantum dot sensitization to obtain a composite titanium dioxide nanotube array. 4) Using the composite titanium dioxide nanotube array obtained in step 3) as the anode, perform secondary anodizing and then calcination to obtain a new layer of titanium dioxide nanotube array. The electrolyte solution is a mixed solution composed of ammonium fluoride, water and ethylene glycol; 5) The sample obtained in step 4) was pretreated by immersing it in a solution of γ-glycidyl oxypropyltrimethoxysilane toluene, and then immersed in an amoxicillin solution for template drug loading, loading amoxicillin into the newly obtained titanium dioxide nanotube array in step 4). 6) Immerse the sample obtained in step 5) in a hexadecyltrimethoxysilane methanol solution and adjust the pH value to 3-6 to obtain a ternary visible light responsive controlled-release drug material based on a double-layer titanium dioxide nanotube array.

2. The preparation method according to claim 1, characterized in that, In step 1), the electrolyte solution contains 0.5–2.0 wt% ammonium fluoride and the volume ratio of water to glycerol is 1:1–3. In step 4), the electrolyte solution contains 0.2–1.0% ammonium fluoride and 1–10% water by volume.

3. The preparation method according to claim 1, characterized in that, In step 1), the anodic oxidation method uses a graphite electrode as the cathode and a titanium sheet as the anode, with an applied DC voltage of 10–80V, and anodizes for 1–10 hours; in step 4), the graphite electrode is used as the cathode, and the composite titanium dioxide nanotube array obtained in step 3) is used as the anode for anodizing, with an applied DC voltage of 10–80V, and anodizes for 10–120 minutes.

4. The preparation method according to claim 1, characterized in that, In step 2), the specific steps of the silver ammonia method are as follows: add ammonia solution dropwise to silver nitrate solution until clear, then add polyvinylpyrrolidone, immerse the titanium dioxide nanotube array prepared in step 1) in it for 1 to 10 minutes, wash away excess silver ions, then immerse it in glucose solution for 1 to 10 minutes, and heat it to 20 to 100°C to obtain the titanium dioxide nanotube array modified with silver nanoparticles.

5. The preparation method according to claim 1, characterized in that, In step 2), the calcination temperature is 200–500℃ and the calcination time is 1–8h; in step 4), the calcination temperature is 200–500℃ and the calcination time is 20–120min.

6. The preparation method according to claim 1, characterized in that, In step 3), the concentration of bismuth nitrate solution is 0.01–0.10 mol / L, and the concentration of sodium sulfide solution is 0.01–0.10 mol / L.

7. The preparation method according to claim 1, characterized in that, In step 3), the titanium dioxide nanotube array is immersed in bismuth nitrate solution for 1 to 20 minutes; and in sodium sulfide solution for 1 to 20 minutes.

8. The preparation method according to claim 1, characterized in that, In step 5), the concentration of the γ-glycidoxypropyltrimethoxysilane toluene solution is 1–30 mmol / L, and the concentration of the amoxicillin solution is 0.01–0.1 mol / L; in step 6), the concentration of hexadecyltrimethoxysilane in the hexadecyltrimethoxysilane methanol solution is 0.1–10 wt%.

9. The preparation method according to claim 1, characterized in that, In step 5), the pretreatment time is 2 to 48 hours; the template drug loading time is 2 to 48 hours.

10. The preparation method according to claim 1, characterized in that, In step 6), the sample obtained in step 5) is immersed in a hexadecyltrimethoxysilane methanol solution for 2 to 6 minutes, and this is repeated 1 to 3 times.

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