Sternberg Katrin, Petersen Svea, Grabow Niels, Senz Volkmar, Meyer zu Schwabedissen Henriette, Kroemer Heyo K, Schmitz Klaus-Peter
Biomed Tech (Berl). 2013 Oct;58(5):417-27. doi: 10.1515/bmt-2012-0049.
Implants providing controlled, local release of active substances are of interest in different medical applications. Therefore, the focus of the present article is the development of implant-associated diffusion- or chemically controlled local drug delivery (LDD) systems based on biodegradable polymeric drug carriers. In this context, we provide new data and review our own recently published data concerning the drug release behavior of diffusion-controlled LDD systems in relation to the kind of polymer, drug content, coating mass/thickness, and layer composition. We demonstrate that polymers allow a wide range of control over the drug release characteristics. In this regard, we show that the glass transition temperature of a polymer has an impact on its drug release. Additionally, the blending of hydrophobic, semicrystalline polymers with amorphous polymers leads to an increase in the rate of drug release compared with the pure semicrystalline polymer. Moreover, the percentage loading of the embedded drug has a considerable effect on the rate and duration of drug release. Furthermore, we discuss chemically controlled LDD systems designed for the release of biomolecules, such as growth factors, as well as nanoparticle-mediated LDD systems. With our own published data on drug-eluting stents, microstents, and cochlear implants, we highlight exemplary implant-associated LDD systems designed to improve implant performance through the reduction of undesirable effects such as in-stent restenosis and fibrosis.
能够实现活性物质可控局部释放的植入物在不同的医学应用中备受关注。因此,本文的重点是基于可生物降解聚合物药物载体开发与植入物相关的扩散控制或化学控制局部药物递送(LDD)系统。在此背景下,我们提供了新的数据,并回顾了我们自己最近发表的有关扩散控制LDD系统药物释放行为的数据,这些行为与聚合物种类、药物含量、涂层质量/厚度和层组成有关。我们证明聚合物能够对药物释放特性进行广泛的控制。在这方面,我们表明聚合物的玻璃化转变温度会对其药物释放产生影响。此外,与纯半结晶聚合物相比,疏水性半结晶聚合物与无定形聚合物的共混会导致药物释放速率增加。此外,嵌入药物的负载百分比对药物释放的速率和持续时间有相当大的影响。此外,我们还讨论了用于释放生物分子(如生长因子)的化学控制LDD系统以及纳米颗粒介导的LDD系统。通过我们自己发表的关于药物洗脱支架、微支架和人工耳蜗的数据,我们重点介绍了一些示例性的与植入物相关的LDD系统,这些系统旨在通过减少诸如支架内再狭窄和纤维化等不良影响来提高植入物性能。