简易冻干法制备二氧化钛纳米管载药涂层的研究

Fabrication of titanium nanotube drug-eluting coating using simplified lyophilization method

目的:探讨简易冻干法制备二氧化钛载药涂层、剂量可控并高效加载药物的可行性。方法:用阳极氧化的方法在纯钛试样表面制备二氧化钛纳米管。用原子力显微镜,场发射电镜,X射线能谱仪,以及接触角测量仪观测表面形貌和特性。采用简易冻干法在纳米管中加载牛血清白蛋白(BSA),平均每一个试样加药量为100μg或200μg(n=5)。加载完成后将表面的蛋白用PBS冲洗,收集冲洗液分析加载效率。试样放入24孔板中,每一试样浸泡在500μl PBS溶液中,孔板放在70 r/min的摇床上,每15 min取出200μl(然后加入200μl新鲜PBS)用于分析释放的量。利用酶联免疫吸附测定法测定药物浓度,分析载药涂层的加载效率及释放规律。结果:二氧化钛纳米管电镜下管径为(100±10)nm,粗糙度为9.1 nm。蛋白加载效率在80%以上;加载100和200μg BSA的试样缓释时间分别在60～75 min和75～90 min。结论:应用简易冻干法制备的二氧化钛纳米管载药涂层方法简单,剂量可控,加载效率高,有望在种植体经皮部位处理中发挥作用。

Objective： To investigate the feasibility of simplified lyophilization in fabrication of titanium nanotube drug-eluting coating with controlled drug dose and high loading efficiency.Methods： Round pure titanium specimens（diameter=10 mm） were anodizated to acquire titanium nanotube surfaces.Then the surface characterization was observed by field-emission scanning electron microscopy（SEM） and atomic force microscopy（AFM）.Bovine serum albumin（BSA） was used as the model drug and filled into the nanotubes by simplified lyophilization at the dose of 100 μg and 200 μg respectively for each sample（n=5）.After the final drying step,the nanotubes of each sample were rinsed by pipetting 500 μl of PBS and the rinsing fluid was collected for the analysis of the loading efficiency.The releasing kinetics of BSA from nanotubes on the coated specimens was studied using enzyme-linked immunosorbent assay.Results： The diameter of titania nanotubes was（100±10） nm and the average roughness was 9.1 nm.The loading efficiency of 100 μg and 200 μg BSA coating groups was 81.2% and 86.7% respectively.Moreover,the 200 μg BSA coating specimens could sustain releasing for 75 to 90 minutes,the 100 μg ones could sustain for 60 to 75 minutes.Conclusion： The controlled loading dose and high loading efficiency can be simultaneously achieved by fabricating titanium nanotube drug-eluting coating via simplified lyophilization.