Department of Biomedical Engineering, National University of Singapore, Singapore 117576, Singapore.
Department of Biomedical Engineering, National University of Singapore, Singapore 117576, Singapore; National Heart Research Institute Singapore, National Heart Center Singapore 169609, Singapore.
Eur J Pharm Biopharm. 2021 Jan;158:72-82. doi: 10.1016/j.ejpb.2020.09.016. Epub 2020 Oct 17.
Interventional therapies such as drug-eluting stents (DES) and drug-coated balloons (DCB) have significantly improved the clinical outcomes of patients with coronary occlusions in recent years. Despite this marked improvement, ischemic cardiovascular disease remains the most common cause of death worldwide. To address this, research efforts are focused on improving the safety and efficacy of the next generation of these devices. However, current experimental methods are unable to account for the influence of atherosclerotic lesions on drug uptake and retention. Therefore, in this study, we used an integrated approach utilizing both in vitro and in silico methods to assess the performance of DCB therapy. This approach was validated against existing in vivo results before being used to numerically estimate the effect of the atheroma. A bolus release of sirolimus was observed with our coating matrix. This, coupled with the rapid saturation of specific and non-specific binding sites observed in our study, indicated that increasing the therapeutic dose coated onto the balloons might not necessarily result in greater uptake and/or retention. Additionally, our findings alluded to an optimal exposure time, dependent on the coating matrix, for the DCBs to be expanded against the vessel. Moreover, our findings suggest that a biphasic drug release profile might be beneficial for establishing and maintaining the saturation of bindings sites within severely occluded vessels. Ultimately, we have demonstrated that computational methods may be capable of assessing the efficacy of DCB therapy as well as predict the influence of atherosclerotic lesions on said efficacy.
近年来，药物洗脱支架（DES）和药物涂层球囊（DCB）等介入治疗方法显著改善了冠状动脉闭塞患者的临床结局。尽管取得了这一显著的改善，但缺血性心血管疾病仍然是全球最常见的死亡原因。为了解决这个问题，研究工作集中在提高下一代这些设备的安全性和有效性。然而，目前的实验方法无法考虑到动脉粥样硬化病变对药物摄取和保留的影响。因此，在这项研究中，我们使用了一种结合体外和计算方法的综合方法来评估 DCB 治疗的性能。在用于数值估计动脉粥样硬化的影响之前，我们使用现有的体内结果对该方法进行了验证。我们的涂层基质观察到了西罗莫司的突释释放。这一点，加上我们研究中观察到的特异性和非特异性结合位点的快速饱和，表明增加涂覆在球囊上的治疗剂量不一定会导致更大的摄取和/或保留。此外，我们的研究结果表明，存在一个最佳的暴露时间，取决于涂层基质，以便 DCB 能够在扩张时对抗血管。此外，我们的研究结果表明，双相药物释放曲线可能有利于在严重闭塞的血管内建立和维持结合位点的饱和。最终，我们已经证明，计算方法可以评估 DCB 治疗的效果，并预测动脉粥样硬化病变对其疗效的影响。
