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

Info

Publication number
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
Authority
CN
China
Prior art keywords
titanium dioxide
nanotube array
dioxide nanotube
tetradecanol
temperature
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201811197640.0A
Other languages
Chinese (zh)
Other versions
CN109289089A (en
Inventor
刘楠楠
谢春玲
陈顺玉
肖秀峰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fujian Normal University
Original Assignee
Fujian Normal University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fujian Normal University filed Critical Fujian Normal University
Priority to CN201811197640.0A priority Critical patent/CN109289089B/en
Publication of CN109289089A publication Critical patent/CN109289089A/en
Application granted granted Critical
Publication of CN109289089B publication Critical patent/CN109289089B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/02—Inorganic materials
    • A61L27/04—Metals or alloys
    • A61L27/06—Titanium or titanium alloys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25D—PROCESSES FOR THE ELECTROLYTIC OR ELECTROPHORETIC PRODUCTION OF COATINGS; ELECTROFORMING; APPARATUS THEREFOR
    • C25D11/00—Electrolytic coating by surface reaction, i.e. forming conversion layers
    • C25D11/02—Anodisation
    • C25D11/26—Anodisation of refractory metals or alloys based thereon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/41—Anti-inflammatory agents, e.g. NSAIDs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/602—Type of release, e.g. controlled, sustained, slow
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2420/00—Materials or methods for coatings medical devices
    • A61L2420/02—Methods for coating medical devices

Abstract

The invention discloses a preparation method of a temperature-controlled intelligent drug release system based on a titanium dioxide nanotube array, and aims to provide the temperature-controlled intelligent drug release system which is characterized in that a titanium sheet is used as an anode, and the titanium dioxide nanotube array is prepared by anodic oxidation; and mixing tetradecanol serving as a temperature control switch and ibuprofen serving as an anti-inflammatory drug in a water bath condition of 50 ℃, and loading the mixture into the titanium dioxide nanotube array by a vacuum drying method. The invention is characterized in that: fundamentally makes anti-inflammatory drug release when the affected part is inflamed according to self organism environment, and the non-inflammation is then released a small amount or not release to reduce or avoid the pathological change that the postoperative leads to because of the inflammation, improve the utilization ratio of medicine simultaneously, avoid the injury of the side effect of some medicines to the human body. The system can be loaded with other anti-inflammatory drugs that are soluble in tetradecanol. And subsequently, on the basis of the research of the system, other materials with good photothermal conversion effect are introduced to design and research and develop the near infrared light-controlled intelligent drug release system.

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. A preparation method of a temperature-controlled intelligent drug release system based on a titanium dioxide nanotube array is characterized by comprising 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: taking a pretreated titanium sheet as an anode and a platinum sheet as a cathode, and 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, wherein the oxidation voltage is 30-70V, and the temperature of the electrolyte solution is 20-50 ℃ to obtain a titanium dioxide nanotube array;
3) preparation of ibuprofen and tetradecanol blends: using tetradecanol as a solvent, ibuprofen as a solute, and fully blending the materials in a mass ratio of 2:1-4:1 under the condition of stirring in a water bath at 50 ℃ to obtain a blend IBU-TD of ibuprofen and tetradecanol;
4) vacuum drying the blend of ibuprofen and tetradecanol IBU-TD: a liquid-transferring gun sucks 25-40 mu L of the blend IBU-TD of ibuprofen and tetradecanol obtained in the step 3) which is fully mixed under the water bath condition, the blend is dripped on the surface of the titanium dioxide nanotube array obtained in the step 2), and the mixture is placed in a vacuum drying oven and is subjected to vacuum drying treatment for 2-4 hours at the temperature of 50-60 ℃; and repeating the operation for 5-9 times to obtain the temperature control intelligent system based on the titanium dioxide nanotube array.
CN201811197640.0A 2018-10-15 2018-10-15 Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array Active CN109289089B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201811197640.0A CN109289089B (en) 2018-10-15 2018-10-15 Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201811197640.0A CN109289089B (en) 2018-10-15 2018-10-15 Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array

Publications (2)

Publication Number Publication Date
CN109289089A CN109289089A (en) 2019-02-01
CN109289089B true CN109289089B (en) 2021-12-28

Family

ID=65162789

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201811197640.0A Active CN109289089B (en) 2018-10-15 2018-10-15 Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array

Country Status (1)

Country Link
CN (1) CN109289089B (en)

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

Also Published As

Publication number Publication date
CN109289089A (en) 2019-02-01

Similar Documents

Publication Publication Date Title
CN109289049B (en) Preparation method of near-infrared light-controlled intelligent drug release system based on titanium dioxide nanotube array
Yi et al. Liquid metal biomaterials: a newly emerging area to tackle modern biomedical challenges
Kaushik et al. Strategies for using polydopamine to induce biomineralization of hydroxyapatite on implant materials for bone tissue engineering
Shivaram et al. Mechanical degradation of TiO2 nanotubes with and without nanoparticulate silver coating
CN104826159A (en) Medical titanium metal implant material and preparation method thereof
CN102525827B (en) Method for preparing medical titanium material with long-acting antibacterial property and good biocompatibility
Liu et al. Conductive nanomaterials for cardiac tissues engineering
CN102560598A (en) Method for preparing medical titanium material with high anti-cancer and antibacterial properties
Li et al. Thermosensitive-hydrogel-coated titania nanotubes with controlled drug release and immunoregulatory characteristics for orthopedic applications
Yarlagadda et al. Recent developments in the Field of nanotechnology for development of medical implants
Kandel et al. Biomimetic cell–substrate of chitosan-cross-linked polyaniline patterning on TiO2 nanotubes enables hBM-MSCs to differentiate the osteoblast cell type
Peng et al. Advances in biomaterials for adipose tissue reconstruction in plastic surgery
Wang et al. Direct current stimulation for improved osteogenesis of MC3T3 cells using mineralized conductive polyaniline
CN103695707A (en) Titanium silver alloy nanotube for surgery fixing apparatus and preparation method thereof
Zhao et al. Potential load-bearing bone substitution material: carbon-fiber-reinforced magnesium-doped hydroxyapatite composites with excellent mechanical performance and tailored biological properties
CN109289089B (en) Preparation method of temperature-controlled intelligent drug release system based on titanium dioxide nanotube array
Bai et al. Fabrication and characterization of gold nanoparticle-loaded TiO 2 nanotube arrays for medical implants
Mondal et al. Hydroxyapatite: A journey from biomaterials to advanced functional materials
Cao et al. Recent advances in two-dimensional nanomaterials for bone tissue engineering
Ganguly et al. Recent advances in nanotubes for orthopedic implants
Kim et al. Development of gelatin-based shape-memory polymer scaffolds with fast responsive performance and enhanced mechanical properties for tissue engineering applications
Mohammed et al. A review on the latest developments of conducting polymer and composite coatings for enhancing biocompatibility and corrosion resistance of metallic biomedical implants
CN106620843A (en) Composite bone cement with bioactivity and antibacterial activity as well as preparation method and application
Govindarajan et al. Graphene: A Multifaceted Carbon-Based Material for Bone Tissue Engineering Applications
CN114099786A (en) Preparation method of exosome-loaded electroactive hydrogel dressing

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant