Sustained Drug Release from Non-eroding Nanoporous Templates
Sustained Drug Release from Non-eroding Nanoporous Templates
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DOI：
10.1002/smll.200901736
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发表时间：
2010-01-18
期刊：
影响因子：
13.3
通讯作者：
Sridhar, Srinivas
中科院分区：
文献类型：
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作者：
Gultepe, Evin;Nagesha, Dattatri;Sridhar, Srinivas
在整形外科、心血管支架和除颤器中，机械坚固的植入物被用于身体的许多不同部位。[1，2]然而，仍有许多问题需要克服，如减少感染、增强植入物结合和防止心血管支架的再狭窄等。一种中心策略是加入治疗药物，以增强植入物并克服所提到的关键问题。[3-5]一种流行的方法是结合加载治疗药物的聚合物涂层。[6，7]然而，在某些情况下，聚合物不是最合适的材料，例如在心血管支架中，聚合物涂层的剥离可能导致血栓形成。[8，9]在这种情况下，有必要有一个不降解或侵蚀的储液罐。无腐蚀纳米多孔氧化物涂层提供了一种有吸引力的替代平台，因为它们是不可腐蚀的，并且它们的纳米特征允许控制洗脱曲线。在此，我们介绍了一种模型药物阿霉素(Dox)从不同的非腐蚀纳米孔涂层中释放的结果。以阳极氧化铝(AAO)和阳极氧化钛(ATO)的形式对药物从这些平台上的释放进行了详细的研究。有许多方法可以在不同的材料上溅射金属，如钛和铝，然后将其阳极化[10，11]，从而为将纳米孔模板集成到植入物或支架上提供了可能性。我们发现，纳米多孔表面可以达到几周的持续释放速率，类似于聚合物平台，但由于它们不能降解，因此没有分层或淋失的风险。我们发现，这些纳米孔平台的缓释动力学可以用活化的表面密度依赖的脱附模型来很好地描述，该模型对于非腐蚀平台似乎是普遍的。体外释放研究是使用磷酸盐缓冲盐水(PBS)进行的，PBS通常用于模拟体内药物释放的条件。[12，13]由于纳米孔平台不受生理条件的影响，与聚合物或水凝胶不同，体内的洗脱动力学基本相同。此外，对于像Dox这样的小分子，酶不会干扰药物，因此生物分子的存在不会改变洗脱动力学。在这项研究中，结果证明，纳米多孔平台可用作非侵蚀性缓释系统，可用作现有植入物的涂层，如心血管支架、矫形/牙科植入物、基准植入物或间隔物。钛、铝及其氧化物的生物相容性已得到很好的证实，多年来它们已被广泛应用于骨科假体和牙科植入物。[14-18]用于药物释放应用的氧化铝纳米孔涂层的一些研究以前已经进行过。[10，19-21]ATO纳米管，尽管与AAO相比是一种相对较新的材料，过去也被研究为药物释放平台。[22，23]研究表明，二氧化钛-纳米管涂层不仅具有生物相容性，而且还支持骨生长。[24-26]尽管以前已经研究过纳米孔涂层的药物释放，但对这些平台的释放动力学和控制它们的动力学缺乏了解。在这里，我们的目的是通过一个模型来解释纳米孔表面的释放动力学，该模型得到了洗脱曲线的系统研究。三种不同类型的平台用于洗脱…
Mechanically robust implants are being used in many different parts of the body for various applications in orthopedics, cardiovascular stents, and defibrillators.[1, 2] However, there are numerous problems to overcome, such as reducing infections, enhancing implant bonding, and preventing restenosis in cardiovascular stents, among others. A central strategy is to incorporate therapeutic agents that can enhance implants and overcome the key problems mentioned.[3–5] A popular approach is to incorporate polymer coatings that are loaded with the therapeutic agent.[6, 7] However, in some cases polymers are not the most suitable materials, such as in cardiovascular stents where delamination of the polymer coating can lead to thrombosis.[8, 9] In those situations it is necessary to have a reservoir that does not degrade or erode. Non-eroding nanoporous oxide coatings offer an attractive alternative platform since they are nonerodible and their nanofeatures allow control of the elution profile. Herein, we present the results for the release of a model drug, doxorubicin (Dox), from different non-eroding nanoporous coatings. Detailed studies of drug release from these platforms in the form of anodic aluminum oxide (AAO) and anodic titanium oxide (ATO) were carried out. There are many approaches to sputter metals, such as titanium and aluminum, on different materials and to anodize them afterwards,[10, 11] thus giving feasibility to the integration of the nanoporous templates on implants or stents. We show that nanoporous surfaces can achieve a sustained release rate over periods of several weeks, similar to polymeric platforms but without the risk of delamination or leaching since they are not degradable. We show that the kinetics of the sustained release from these nanoporous platforms is well described by an activated surface-density-dependent desorption model, which appears to be universal for non-eroding platforms. The release studies were performed in vitro using phosphate-buffered saline (PBS), which is commonly employed to simulate in vivo conditions for drug release.[12, 13] The elution kinetics is fundamentally the same in vivo since the nanoporous platforms are not affected by the physiological conditions, unlike their polymeric or hydrogel counterparts. Besides, in the case of small molecules such as Dox, enzymes would not interfere with the drug and hence the elution kinetics is not altered by the presence of the biomolecules. In this study, the results prove that the nanoporous platforms can be used as non-eroding sustained-release systems that can be utilized as coatings on currently available implants, such as cardiovascular stents, orthopedic/dental implants, fiducial implants, or spacers.The biocompatibility of titanium, aluminum, and their oxides has already been well established and they have been used widely in orthopedic prostheses and dental implants for years.[14–18] Some studies of nanoporous coatings of alumina for drug-release applications have been carried out before.[10, 19–21] ATO nanotubes, although a relatively new material compared to AAO, have also been investigated as drug-release platforms in the past.[22, 23] Studies have shown that titania-nanotube coatings are not only biocompatible but also support bone growth.[24–26] Although drug release from nanoporous coatings has been studied before, there is a lack of understanding of the release kinetics from these platforms and the dynamics governing them. Herein, our aim is to explain the release kinetics from nanoporous surfaces by a model that is supported with a systematic study of elution profiles. Three different types of platforms were used for the elution …