Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Sklodowska 34 St., 41-819 Zabrze, Poland.
Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Sklodowska 34 St., 41-819 Zabrze, Poland.
Eur J Pharm Biopharm. 2018 Nov;132:41-49. doi: 10.1016/j.ejpb.2018.08.015. Epub 2018 Sep 1.
Despite extensive development of bioresorbable drug-eluting vascular scaffolds it is still challenging to achieve controlled drug delivery. The lack of capacity for adjusting the drug dose and inadequate release behavior are one of the main reasons of the side effects. However, so far, mainly biodegradable drug-eluting coatings of metallic stents have been studied in regard to explain drug release mechanisms. The objective of this study was to develop degradable polymer coatings applicable to bioresorbable polymer-based scaffolds. Moreover, a detailed analysis of sirolimus release and scaffold degradation has been conducted. Coating layers of the same composition were applied by the same method on the surface of two different kinds of scaffolds in order to explain the effect of scaffold structure on release process. The developed coatings showed controlled release of antiproliferative agent with elimination of burst effect. However, differences in drug release profile from two kinds of scaffolds were observed. Scaffold composed of polymer with higher lactide content showed slower and bi-phasic, erosion-controlled release of sirolimus. On the contrary, sirolimus release from scaffold composed of polymer with lower content of lactide was mainly controlled by diffusion. These results demonstrate that characteristics of scaffold is another crucial factor that must be considered in further development of bioresorbable vascular scaffolds (BRS) with controlled release of antiproliferative agent.
尽管生物可吸收药物洗脱血管支架已经得到了广泛的发展，但仍然难以实现药物的控制释放。缺乏调整药物剂量的能力和不理想的释放行为是副作用的主要原因之一。然而，到目前为止，主要研究了金属支架的可生物降解药物洗脱涂层，以解释药物释放机制。本研究的目的是开发适用于生物可吸收聚合物支架的可降解聚合物涂层。此外，还对西罗莫司的释放和支架降解进行了详细分析。相同组成的涂层通过相同的方法涂覆在两种不同类型的支架表面上，以解释支架结构对释放过程的影响。所开发的涂层表现出对有丝分裂抑制剂的控制释放，消除了突释效应。然而，从两种支架中观察到药物释放曲线的差异。由具有较高丙交酯含量的聚合物组成的支架表现出较慢的双相、侵蚀控制的西罗莫司释放。相反，由丙交酯含量较低的聚合物组成的支架中西罗莫司的释放主要由扩散控制。这些结果表明，支架的特性是进一步开发具有控制释放有丝分裂抑制剂的生物可吸收血管支架（BRS）的另一个关键因素。
