How does the Nature of an Excipient and an Atheroma Influence Drug-Coated Balloon Therapy?

The advent of drug-eluting stents and drug-coated balloons have significantly improved the clinical outcome of patients with vascular occlusions. However, ischemic vascular disease remains the most common cause of death worldwide. Improving the current treatment modalities demands a better understanding of the processes which govern drug uptake and retention in blood vessels. In this study, we evaluated the influence of urea and butyryl-trihexyl citrate, as excipients, on the efficacy of drug-coated balloon therapy. An integrated approach, utilizing both in-vitro and in-silico methods, was used to quantify the tracking loss, vessel adhesion, drug release, uptake, and distribution associated with the treatment. Moreover, a parametric study was used to evaluate the potential influence of different types of lesions on drug-coated balloon therapy. Despite the significantly higher tracking loss (urea: 35.5% vs. butyryl-trihexyl citrate: 8.13%) observed in the urea-based balloons, the drug uptake was almost two times greater than with its hydrophobic counterpart. Non-calcified lesions were found to delay the transmural propagation of sirolimus while calcification was shown to limit the retentive potential of lesions. Ultimately this study helps to elucidate how different excipients and types of lesions may influence the efficacy of drug-coated balloon therapy.

Shape memory micro-anchors with magnetic guidance for precision micro-vascular deployment.

Transcatheter medical micro-devices through circulatory system show great potential for therapy but lack strategies to stably anchor them at the desired site in vascularized tissues to take actions. Here a shape memory functionalized biodegradable magnetic micro-anchor (SM2A) is developed to achieve magnetic guided endovascular localization through precisely controlled shape transformation. The SM2A comprises anisotropic polylactide-based microparticle embedded with superparamagnetic Fe3O4 nanoparticles, exhibiting thermally activated tunable shape recovery modes at a body-friendly temperature range to accomplished an efficient endovascular anchoring effect in both decellularized liver organ and rabbit ear embolization models. The SM2A can be anchored at the target micro-vessel, exhibiting a controlled radial expansion of the vessel wall yielding with estimated stresses of 7-26 kPa in contact stress and 38-218 kPa in von Mises stress. The SM2A is a promising platform to incorporate diagnostic or therapeutic agents for precision deployment and in-situ action.

Assessing the influence of atherosclerosis on drug coated balloon therapy using computational modelling.

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.