CN109289089B - Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array - Google Patents

Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array Download PDF

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CN109289089B
CN109289089B CN201811197640.0A CN201811197640A CN109289089B CN 109289089 B CN109289089 B CN 109289089B CN 201811197640 A CN201811197640 A CN 201811197640A CN 109289089 B CN109289089 B CN 109289089B
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titanium dioxide
dioxide nanotube
tetradecanol
nanotube array
temperature
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CN109289089A (en
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刘楠楠
谢春玲
陈顺玉
肖秀峰
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Fujian Normal University
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Abstract

本发明公开一种基于二氧化钛纳米管阵列的温控智能释药系统的制备方法，其目的是提供一种温控智能释药系统，其特点为以钛片为阳极，阳极氧化制备二氧化钛纳米管阵列；以十四醇为温控开关，布洛芬为消炎药物，将二者在50℃水浴条件下进行共混，经真空干燥法载入二氧化钛纳米管阵列。本发明特点在于：从根本上根据自身机体环境使消炎药物在患处发炎时释放，不发炎则少量释放或不释放，从而减小或避免术后因发炎导致的病变，同时提高药物利用率，避免部分药物的副作用对人体的伤害。此系统可载入其他可溶于十四醇的消炎药物。且后续，将在此系统的研究基础上，引入具有良好的光热转换效应的其他材料，进行近红外光控智能释药系统的设计与研发。

Figure 201811197640

The invention discloses a preparation method of a temperature-controlled intelligent drug release system based on titanium dioxide nanotube arrays, and aims to provide a temperature-controlled intelligent drug release system, which is characterized in that titanium dioxide nanotube arrays are prepared by anodizing titanium sheets as anodes. ; Using tetradecanol as a temperature control switch and ibuprofen as an anti-inflammatory drug, the two were blended in a water bath at 50°C, and loaded into the titanium dioxide nanotube array by vacuum drying. The present invention is characterized in that: the anti-inflammatory drug is fundamentally released when the affected part is inflamed according to its own body environment, and a small amount or no release is released when the affected part is not inflamed, thereby reducing or avoiding postoperative pathological changes caused by inflammation, while improving the drug utilization rate, avoiding The side effects of some medicines are harmful to the human body. The system can be loaded with other tetradecanol-soluble anti-inflammatory drugs. In the future, based on the research of this system, other materials with good photothermal conversion effect will be introduced to design and develop a near-infrared light-controlled intelligent drug delivery system.

Figure 201811197640

Description

Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array
Technical Field
The invention belongs to the technical field of preparation of bone repair biomaterials and drug sustained-release carriers, and particularly relates to a method for preparing a temperature-controlled intelligent drug release system based on a titanium dioxide nanotube array.
Background
In the orthopedic (implantation) operation, most of the adopted implantation materials are titanium and its alloy which are biomedical materials with high use frequency and good effect at present, and these materials have many advantages which other biomedical materials do not have, and the comprehensive performance is also the most excellent, for example, good biocompatibility, corrosion resistance, fatigue resistance, and low elastic modulus which is close to the corresponding tissues of human bones, teeth, etc. Therefore, in recent years, the application fields and the application degrees of the materials are wide, and the materials are considered to be the most ideal biomedical metal materials with the most application prospects at present. However, titanium and titanium alloys have poor in-vivo osteogenesis inducing capability, are difficult to form firm bone bonding with human tissues, form fiber wrapping to be rejected by human bodies, and have yet to be further improved in wear resistance, so that many researchers in the recent years modify the surfaces of titanium and titanium alloys to endow the titanium and titanium alloys with more excellent properties.
Among the modifications, the most studied is to prepare a titanium dioxide nanotube array with one open end and one closed end on the titanium-based surface by an anodic oxidation method. The process has relatively simple preparation process, and the highly ordered TiO is constructed on the surface of the titanium metal2The nanotube array also has the advantages of ordered array height, controllable tube diameter, firmer combination of the nanotubes and the substrate, and the like. The material has a nano-scale porous shape, is suitable for adhesion and growth of various cells, and can also be used for loading antibacterial, anti-inflammatory or bone growth promoting drugs into the material by utilizing the unique structure, so that the material has functionality, namely a local drug release function, and meanwhile, compared with intravenous injection and oral administration, the structure of the material has incomparable advantages, such as directional drug release, slow release effect and the like. However, such bone implant materials still cannot meet the requirement of intellectualization of the drug release process, i.e. drug release on demand. In order to achieve the purpose, many scholars focus on the research of intelligent drug delivery systems, and the existing intelligent drug delivery systems mainly comprise the following systems: 1. ultraviolet and visible light controlled release, 2, radio frequency controlled release, 3, and external magnetic field controlled release. However, in these systems, there is no direct disease manifestation from inflammation of affected parts (temperature of affected parts is increased when the affected parts are inflamed), and only controlled release is basically performed by the actual environment of human bodyThe intelligent medicine release system can ensure that the medicine can be released intelligently according to the actual environment of the human body as required after the system is implanted, thereby ensuring that the intelligent medicine release aim is achieved and improving the medicine utilization rate.
Tetradecanol (1-Tetradecanol, C)14H30O, TD for short), the melting point is 37.8 ℃, the material has good biocompatibility, does not have complex reaction process when taking part in the reaction, is degradable, and is an environment-friendly phase-change material. In conclusion, tetradecanol can be used as a basic substance of a temperature control system well.
Ibuprofen (Ibuprofen) has the chemical name of 2- (4-isobutylphenyl) propionic acid and the molecular formula C13H18O2It is a non-steroidal anti-inflammatory drug (NSAID), hereinafter referred to as IBU. It is often used to relieve symptoms such as arthritis, menstrual pain, fever, etc. It is also an analgesic, especially for pain caused by inflammation.
Disclosure of Invention
The invention aims to provide a construction method of a temperature control intelligent system based on a titanium dioxide nanotube array by utilizing the phase-changeable property of tetradecanol.
The invention aims to realize the purpose, and the preparation method of the temperature-controlled intelligent drug release system based on the titanium dioxide nanotube array is characterized in that: preparing a titanium dioxide nanotube array by using a titanium sheet as an anode and performing anodic oxidation; the method is characterized in that Tetradecanol (TD) is used as a temperature control basis, Ibuprofen (IBU) is used as an anti-inflammatory drug, and a mixture of the tetradecanol and the ibuprofen is loaded into a titanium dioxide nanotube array through a vacuum drying method.
The titanium dioxide nanotube array prepared by anodic oxidation is prepared by the following steps:
1) titanium sheet pretreatment: polishing the titanium sheet to be smooth, and polishing the titanium sheet in HF and HNO3Etching the mixed acid solution for 10-30 s, leaching the mixed acid solution with distilled water, and drying the mixed acid solution at 50 ℃;
2) preparing a titanium dioxide nanotube array: and (2) carrying out anodic oxidation for 2-24 h in an electrolyte solution containing 0.20-0.60 wt% of ammonium fluoride in a glycerol/water system by taking the pretreated titanium sheet as an anode and a platinum sheet as a cathode, wherein the oxidation voltage is 30-70V, and the temperature of the electrolyte solution is 20-50 ℃ to obtain the titanium dioxide nanotube array.
The preparation method of the blend of tetradecanol and ibuprofen comprises the following steps: mixing tetradecanol and ibuprofen in a mass ratio of 2:1-4:1 under the condition of water bath magnetic stirring at 50-60 ℃ to form a mixture; 2) loading a titanium dioxide nanotube array by a vacuum drying method, in the process, 25 to 40 mu L of the mixture prepared in the step 1) is taken each time, the mixture is dripped into the preheated titanium dioxide nanotube array while the mixture is hot, the titanium dioxide nanotube array is placed in a vacuum drying oven at the temperature of between 50 and 60 ℃ for vacuum drying for 2 to 4 hours, and the operation is repeated for 5 to 9 times, so that the intelligent temperature-controlled drug release system taking tetradecanol as the temperature control basis is obtained.
Specifically, the invention adopts the following technical scheme: the preparation method of the near-infrared light-controlled intelligent drug release system based on the titanium dioxide nanotube array is characterized in that: and (2) placing the pretreated titanium sheet at an anode and a foil at a cathode by using an anodic oxidation method, and oxidizing in an electrolyte of a glycerol/water system to form a titanium dioxide nanotube array on the surface of the titanium sheet. The mixture of ibuprofen and tetradecanol is blended according to a certain proportion, and the blend is loaded into a nanotube array through a vacuum drying method, so that a temperature control intelligent system based on a titanium dioxide nanotube array is constructed. The method comprises the following specific steps:
1) titanium sheet pretreatment: polishing the titanium sheet to be smooth, and polishing the titanium sheet in HF and HNO3Etching the mixed acid solution for 10-30 s, leaching the mixed acid solution with distilled water, and drying the mixed acid solution at 50 ℃.
2) Preparing a titanium dioxide nanotube array: and (2) carrying out anodic oxidation for 2-24 h in an electrolyte solution containing 0.20-0.60 wt% of ammonium fluoride in a glycerol/water system by taking the pretreated titanium sheet as an anode and a platinum sheet as a cathode, wherein the oxidation voltage is 30-70V, and the temperature of the electrolyte solution is 20-50 ℃ to obtain the titanium dioxide nanotube array.
3) Preparation of ibuprofen and tetradecanol blends: and fully blending the solution by using tetradecanol as a solvent and ibuprofen as a solute in a mass ratio of 2:1-4:1 under the condition of stirring in a water bath at 50 ℃ to obtain a blend of the ibuprofen and the tetradecanol, which is marked as IBU-TD.
4) Vacuum drying method loading IBU-TD: and (3) sucking 25-40 mu L of IBU-TD fully mixed under the water bath condition by a liquid transfer gun, dripping the IBU-TD on the surface of the titanium dioxide nanotube array, putting the titanium dioxide nanotube array in a vacuum drying box, and carrying out vacuum drying treatment for 2-4h at 50-60 ℃. And repeating the operation for 5-9 times to obtain the temperature control intelligent system based on the titanium dioxide nanotube array.
The invention has the beneficial effects that: the temperature control intelligent system based on the titanium dioxide nanotube array obtained by adopting the scheme has the following characteristics: the porous structure on the surface of the system is beneficial to the growth and adhesion of osteoblasts; the anti-inflammatory drug which can be mutually dissolved with TD can be loaded for the construction of the system related by the invention, and drug molecules are loaded for the intelligent and effective drug release according to the temperature of the affected part of a human body; the system can rapidly release anti-inflammatory drugs required by inflammation of affected parts at high temperature (39 ℃/40 ℃) and release little or no drugs at normal body temperature (37 ℃); has high drug utilization rate.
Drawings
Fig. 1a is a surface micro-topography of a titanium dioxide nanotube array obtained by anodic oxidation in embodiment 1 of the present invention.
Fig. 1b is a cross-sectional micro-topography of a titanium dioxide nanotube array obtained by anodic oxidation in embodiment 1 of the present invention.
FIG. 2a is a surface micro-topography of a titanium dioxide nanotube array loaded into IBU-TD by a vacuum drying method in embodiment 2 of the present invention.
FIG. 2b is a cross-sectional micro-topography of the titanium dioxide nanotube array loaded into IBU-TD by vacuum drying in embodiment 2 of the present invention.
FIG. 3 is a periodic release profile of a mesophilic controlled release drug system in accordance with embodiment 3 of the present invention.
Detailed Description
Example 1
Using titanium as substrate, grinding with metallographic abrasive paper to be smooth, ultrasonic cleaning in acetone, and treating with HF and HNO3Etching the mixed acid solution (volume ratio is 1: 15), leaching with distilled water and performing ultrasonic treatment, and drying at 50 ℃. Using a pretreated titanium sheet as an anode and a platinum sheet as a cathode, and adding 0.30wt% of ammonium fluoride-containing glycerol/water (the volume ratio of glycerol to water is 1: 7) into the titanium sheet and the platinum sheetThe titanium dioxide nanotube array is prepared by using an electrolyte solution, anodizing for 24 hours under the voltage of 60V, taking out, leaching with distilled water, and drying in air, wherein the titanium dioxide nanotube array is obtained, the micro-topography is shown in figures 1a and 1b, the nanotubes are tightly and regularly arranged, and the tube diameter is about 210 nm.
Example 2
Using titanium as substrate, grinding with metallographic abrasive paper to be smooth, ultrasonic cleaning in acetone, and treating with HF and HNO3Etching the mixed acid solution (volume ratio is 1: 15), leaching with distilled water and performing ultrasonic treatment, and drying at 50 ℃. Taking a pretreated titanium sheet as an anode, a platinum sheet as a cathode, anodizing for 24 hours under the voltage of 60V by taking a glycerol/water (the volume ratio of glycerol to water is 1: 7) system containing 0.30wt% of ammonium fluoride as an electrolyte solution, taking out, leaching with distilled water, and airing in the air to obtain the titanium dioxide nanotube array, wherein the micro-topography is shown in figures 1a and 1b, the nanotubes are closely arranged and regular, and the tube diameter is about 210 nm.
0.01g of Ibuprofen (IBU) and 0.02g of Tetradecanol (TD) are heated in a water bath at 50 ℃ and continuously stirred until the two are mild and uniform, and the mixture is placed in a water bath kettle and kept at 50 ℃ to obtain a blend of ibuprofen and tetradecanol (IBU-TD). And (3) sucking 25 mu L of prepared IBU-TD by a liquid transfer gun, dripping the IBU-TD on the surface of the titanium dioxide nanotube array to ensure that the IBU-TD is uniformly distributed, and placing the titanium dioxide nanotube array in a vacuum drying oven at 60 ℃ for vacuum drying for 3 hours. And repeating the operation for 5 times to obtain the temperature control intelligent system based on the titanium dioxide nanotube array. The surface morphology is shown in FIG. 2a, the surface is covered with IBU-TD, the aperture is reduced, and the sectional view 2b shows that the IBU-TD has penetrated into the nanotube and successfully loads the nanotube.
Example 3
Using titanium as substrate, grinding with metallographic abrasive paper to be smooth, ultrasonic cleaning in acetone, and treating with HF and HNO3Etching the mixed acid solution (volume ratio is 1: 15), leaching with distilled water and performing ultrasonic treatment, and drying at 50 ℃. Taking a pretreated titanium sheet as an anode, a platinum sheet as a cathode, anodizing for 24 hours under the voltage of 60V by taking a glycerol/water (the volume ratio of glycerol to water is 1: 7) system containing 0.30wt% of ammonium fluoride as an electrolyte solution, taking out, leaching by using distilled water, and airing in the air to obtain the sodium titanium dioxideThe micro-topography of the rice pipe array is shown in fig. 1a and 1b, the arrangement of the nano pipes is tight and regular, and the pipe diameter is about 210 nm.
0.1g IBU and 0.2g TD were heated in a 50 ℃ water bath with constant stirring until both were mild and homogeneous, and placed in a water bath kettle to maintain 50 ℃ to obtain a blend of ibuprofen and tetradecanol (IBU-TD). And (3) sucking 25 mu L of prepared IBU-TD by a liquid transfer gun, dripping the IBU-TD on the surface of the titanium dioxide nanotube array to ensure that the IBU-TD is uniformly distributed, and placing the titanium dioxide nanotube array in a vacuum drying oven at 60 ℃ for vacuum drying for 3 hours. And repeating the operation for 5 times to obtain the temperature control intelligent system based on the titanium dioxide nanotube array. The surface morphology is shown in FIG. 2a, the surface is covered with IBU-TD, the aperture is reduced, and the sectional view 2b shows that the IBU-TD has penetrated into the nanotube and successfully loads the nanotube.
After successful preparation of the system, the system was placed in PBS for temperature swing testing. As can be seen from the release curve 3, the constructed system has good temperature control release performance and can be released repeatedly.

Claims (1)

1.一种基于二氧化钛纳米管阵列的温控智能释药系统的制备方法，其特征在于：1. a preparation method based on the temperature-controlled intelligent drug release system of titanium dioxide nanotube array, is characterized in that: 1）钛片预处理：将钛片打磨至光滑，并在HF和 HNO3的混合酸溶液中刻蚀10~30s，用蒸馏水淋洗，50℃烘干；1) Titanium sheet pretreatment: Polish the titanium sheet until smooth, etch it in a mixed acid solution of HF and HNO 3 for 10~30s, rinse with distilled water, and dry at 50°C; 2）二氧化钛纳米管阵列的制备：以预处理好的钛片为阳极，铂片为阴极，在含氟化铵0.20~0.60 wt% 的甘油/水体系的电解质溶液中进行阳极氧化2~24h，氧化电压为30~70V，电解液温度为20~50℃即得二氧化钛纳米管阵列；2) Preparation of TiO2 nanotube arrays: The pretreated titanium sheet was used as the anode and the platinum sheet was used as the cathode, and anodized in an electrolyte solution containing 0.20-0.60 wt% ammonium fluoride in a glycerol/water system for 2-24 h. The oxidation voltage is 30~70V, and the electrolyte temperature is 20~50°C to obtain the titanium dioxide nanotube array; 3）布洛芬和十四醇共混物的制备：以十四醇为溶剂，以布洛芬为溶质，质量比2:1-4:1于50℃水浴搅拌条件下进行充分共混，即得布洛芬和十四醇的共混物IBU-TD； 3) Preparation of a blend of ibuprofen and tetradecanol: using tetradecanol as a solvent, ibuprofen as a solute, and a mass ratio of 2:1-4:1 is fully blended under the condition of stirring in a 50°C water bath, That is, the blend IBU-TD of ibuprofen and tetradecanol is obtained; 4）真空干燥法载入布洛芬和十四醇的共混物IBU-TD：移液枪吸取水浴条件下充分混合的步骤3）获得的布洛芬和十四醇的共混物IBU-TD 25μL-40μL，滴加于步骤2）获得的二氧化钛纳米管阵列的表面，置于真空干燥箱内，于50-60℃，真空干燥处理2-4h；重复上述操作5-9次，得基于二氧化钛纳米管阵列的温控智能系统。 4) Loading the blend of ibuprofen and tetradecanol into IBU-TD by vacuum drying: the step 3) of the obtained blend of ibuprofen and tetradecanol was mixed well under water bath conditions by pipetting the IBU-TD TD 25μL-40μL, dropwise added to the surface of the titanium dioxide nanotube array obtained in step 2), placed in a vacuum drying oven, and vacuum-dried at 50-60 ℃ for 2-4h; repeat the above operation 5-9 times, based on Temperature-controlled intelligent system of titanium dioxide nanotube arrays.
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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6120789A (en) * 1995-10-27 2000-09-19 Atrix Laboratories, Inc. Non-polymeric sustained release delivery system
CN1732022A (en) * 2002-12-30 2006-02-08 血管技术国际股份公司 Silk stent grafts
CN102220616A (en) * 2011-05-26 2011-10-19 东南大学 Method for preparing titanium dioxide nanotube array
CN103110981A (en) * 2013-01-10 2013-05-22 内蒙金属材料研究所 Method for preparing antibacterial active titanium oxide nanotube array composite coating material
CN104203293A (en) * 2012-02-07 2014-12-10 加利福尼亚大学董事会 Products of manufacture having tantalum coated nanostructures, and methods of making and using them
CN106729964A (en) * 2016-12-02 2017-05-31 江苏师范大学 It is a kind of to have promoting bone growing concurrently and suppress titania nanotube of bone resorption and preparation method thereof
CN107190300A (en) * 2017-06-07 2017-09-22 福建师范大学 The preparation method of mesoporous hydroxyapatite/Nano tube array of titanium dioxide composite

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6120789A (en) * 1995-10-27 2000-09-19 Atrix Laboratories, Inc. Non-polymeric sustained release delivery system
CN1732022A (en) * 2002-12-30 2006-02-08 血管技术国际股份公司 Silk stent grafts
CN102220616A (en) * 2011-05-26 2011-10-19 东南大学 Method for preparing titanium dioxide nanotube array
CN104203293A (en) * 2012-02-07 2014-12-10 加利福尼亚大学董事会 Products of manufacture having tantalum coated nanostructures, and methods of making and using them
CN103110981A (en) * 2013-01-10 2013-05-22 内蒙金属材料研究所 Method for preparing antibacterial active titanium oxide nanotube array composite coating material
CN106729964A (en) * 2016-12-02 2017-05-31 江苏师范大学 It is a kind of to have promoting bone growing concurrently and suppress titania nanotube of bone resorption and preparation method thereof
CN107190300A (en) * 2017-06-07 2017-09-22 福建师范大学 The preparation method of mesoporous hydroxyapatite/Nano tube array of titanium dioxide composite

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