AZ81镁合金表面微弧氧化改性及涂层的药物释放研究
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摘要
镁合金因其优异的生物相容性和生物可降解性,被认为是潜在的人体植入材料,可用于制备新型冠状动脉支架。本文研究基于具有双重可控释放性能要求的可吸收镁合金支架,设计一种新型结构的表面涂层,并系统研究了该涂层对于镁离子以及药物分子的双重控制释放功能。
本研究采用微弧氧化法改性镁合金基体,通过不同氧化电流密度下的微弧氧化改性效果的对比对氧化机理进行初步探讨;Hank’s模拟体液中的电化学测试及浸泡实验对改性效果进行表征。扫描电镜结果表明,改性后基体表面存在许多微孔,且随着氧化电流的增大,孔洞数目减小,但直径增大,随后的极化曲线、阻抗能谱测试表明改性后的试样相较于空白基体,耐蚀性得到一定提高,并呈现出先增后减的变化趋势。XRD测试分析了改性陶瓷层的成分,主要由MgO、Mg、Mg2SiO4这几相组成。浸泡实验表明改性后的基体其镁离子释放速率能维持在一个相对稳定的水平,可以实现镁合金的可控降解。
PLGA作为高分子载药涂层,紫杉醇为装载药物,对药物释放规律进行研究。载药涂层DSC和红外光谱数据表明,在8~12%的药物浓度范围内,紫杉醇均匀分散在PLGA体系中。静态药物释放实验表明,PLGA可使紫杉醇长期持续释放, 50天后,药物释放率基本都在30%左右。PLGA载药涂层药物释放机制研究表明,释放首先主要由扩散控制,而后由PLGA基体降解控制。
采用聚乙二醇(PEG)作为增塑剂研究其对药物释放性能的影响,结果显示: PEG的添加,加速PLGA膜的降解。药物释放实验表明,添加PEG能够提高载药膜药物释放能力,随PEG含量的增加,药物释放率增加。
不同LA:GA比例的PLGA作为控释层,药物释放实验表明控释层能显著地降低紫杉醇的释放速率,且随着GA比例的增大,控释效果减弱。
运用血小板粘附实验测试PLGA载药膜的血液相容性,结果表明加入了紫杉醇的PLGA膜表面没有大规模的血小板聚集现象,粘附数目明显减小且没有出现严重的血小板变形现象,显示出载药膜良好的血液相容性
Magnesium alloy is a kind of potential implant biomaterial due to their good biocompatibility and biodegradability; it is possible to develop a new type of coronary artery stent. This research taking into account the dual controlled release of drug and magnesium ions, a new type of coating on magnesium alloys was designed to meet these requirements, and the release property was studied systematically.
In this study, micro-arc oxidation was used to modify the magnesium’s surfaces; a preliminary study of oxidation mechanism was taken by the contrast of the modified effect of the samples which were treated with different oxidation current density. Electrochemical tests in Hank’s simulated body fluid and immersion test were used to characterize the modification effect. SEMs showed that there were many pores on the surface of the modified samples, and with the oxidation current increased, the number of the pores decreased, the pores’diameter increased. Then the polarization and impedance spectroscopy tests showed that compared to the bare samples, the modified ones had a certain increase in corrosion resistance, showed a trend that first increased and then decreased.XRD test showed the modified ceramic layer was comprised of the phases such as MgO and Mg2SiO4 mainly. Immersion test showed that the magnesium release rate of the modified ones can be maintained at a stable level relatively, it can achieve the target of controlled degradation of magnesium alloy in some way.
By use of PLGA as drug-loaded coating, Taxol as drug,the drug release profile was studied. DSC and infrared spectral of the drug-loaded coating showed that Taxol can be dispersed in the polymer system evenly when the concentration of drug ranged from 8% to 12%. In static drug release experiment, the results showed Taxol could be gradually release in a long time, and the cumulative release rate after 50 days reached approximately 30%. The study of release mechanism showed that the paclitaxel release in first stage was dominated by diffusion, and then shifted to degradation-controlled stage.
The influence on the drug release by the addition of PEG as plasticizer was investigated. The results showed that PEG was indeed able to accelerate the degradation of PLGA films, and with the increasing of the content of PEG, the rate of drug release increased.
Different LA: GA ratio of PLGAs were used as the controlled release layer, drug release experiments showed that the controlled release layer can significantly reduced the release rate of paclitaxel, and the controlled-release effect was weaker as the proportion of PGA increasing.
The platelet adhesion experiment was used to evaluate the blood compatibility of PLGA drug-carrying film, the results showed that there were no large-scale platelet aggregation on the surface of PLGA film with the adding of the paclitaxel, the number of adhesion platelets was significantly reduced and no severe deformation was found , showing that the drug-carrying film’s good blood compatibility
本研究采用微弧氧化法改性镁合金基体,通过不同氧化电流密度下的微弧氧化改性效果的对比对氧化机理进行初步探讨;Hank’s模拟体液中的电化学测试及浸泡实验对改性效果进行表征。扫描电镜结果表明,改性后基体表面存在许多微孔,且随着氧化电流的增大,孔洞数目减小,但直径增大,随后的极化曲线、阻抗能谱测试表明改性后的试样相较于空白基体,耐蚀性得到一定提高,并呈现出先增后减的变化趋势。XRD测试分析了改性陶瓷层的成分,主要由MgO、Mg、Mg2SiO4这几相组成。浸泡实验表明改性后的基体其镁离子释放速率能维持在一个相对稳定的水平,可以实现镁合金的可控降解。
PLGA作为高分子载药涂层,紫杉醇为装载药物,对药物释放规律进行研究。载药涂层DSC和红外光谱数据表明,在8~12%的药物浓度范围内,紫杉醇均匀分散在PLGA体系中。静态药物释放实验表明,PLGA可使紫杉醇长期持续释放, 50天后,药物释放率基本都在30%左右。PLGA载药涂层药物释放机制研究表明,释放首先主要由扩散控制,而后由PLGA基体降解控制。
采用聚乙二醇(PEG)作为增塑剂研究其对药物释放性能的影响,结果显示: PEG的添加,加速PLGA膜的降解。药物释放实验表明,添加PEG能够提高载药膜药物释放能力,随PEG含量的增加,药物释放率增加。
不同LA:GA比例的PLGA作为控释层,药物释放实验表明控释层能显著地降低紫杉醇的释放速率,且随着GA比例的增大,控释效果减弱。
运用血小板粘附实验测试PLGA载药膜的血液相容性,结果表明加入了紫杉醇的PLGA膜表面没有大规模的血小板聚集现象,粘附数目明显减小且没有出现严重的血小板变形现象,显示出载药膜良好的血液相容性
Magnesium alloy is a kind of potential implant biomaterial due to their good biocompatibility and biodegradability; it is possible to develop a new type of coronary artery stent. This research taking into account the dual controlled release of drug and magnesium ions, a new type of coating on magnesium alloys was designed to meet these requirements, and the release property was studied systematically.
In this study, micro-arc oxidation was used to modify the magnesium’s surfaces; a preliminary study of oxidation mechanism was taken by the contrast of the modified effect of the samples which were treated with different oxidation current density. Electrochemical tests in Hank’s simulated body fluid and immersion test were used to characterize the modification effect. SEMs showed that there were many pores on the surface of the modified samples, and with the oxidation current increased, the number of the pores decreased, the pores’diameter increased. Then the polarization and impedance spectroscopy tests showed that compared to the bare samples, the modified ones had a certain increase in corrosion resistance, showed a trend that first increased and then decreased.XRD test showed the modified ceramic layer was comprised of the phases such as MgO and Mg2SiO4 mainly. Immersion test showed that the magnesium release rate of the modified ones can be maintained at a stable level relatively, it can achieve the target of controlled degradation of magnesium alloy in some way.
By use of PLGA as drug-loaded coating, Taxol as drug,the drug release profile was studied. DSC and infrared spectral of the drug-loaded coating showed that Taxol can be dispersed in the polymer system evenly when the concentration of drug ranged from 8% to 12%. In static drug release experiment, the results showed Taxol could be gradually release in a long time, and the cumulative release rate after 50 days reached approximately 30%. The study of release mechanism showed that the paclitaxel release in first stage was dominated by diffusion, and then shifted to degradation-controlled stage.
The influence on the drug release by the addition of PEG as plasticizer was investigated. The results showed that PEG was indeed able to accelerate the degradation of PLGA films, and with the increasing of the content of PEG, the rate of drug release increased.
Different LA: GA ratio of PLGAs were used as the controlled release layer, drug release experiments showed that the controlled release layer can significantly reduced the release rate of paclitaxel, and the controlled-release effect was weaker as the proportion of PGA increasing.
The platelet adhesion experiment was used to evaluate the blood compatibility of PLGA drug-carrying film, the results showed that there were no large-scale platelet aggregation on the surface of PLGA film with the adding of the paclitaxel, the number of adhesion platelets was significantly reduced and no severe deformation was found , showing that the drug-carrying film’s good blood compatibility
引文
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