Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
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DOI：
10.3390/molecules25071596
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发表时间：
2020-04-01
期刊：
影响因子：
4.6
通讯作者：
Yazdani, Saami K.
中科院分区：
文献类型：
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作者：
Goel, Emily;Erwin, Megan;Yazdani, Saami K.
背景：药物包被气球（DCBs）在赋形剂的辅助下输送抗增殖药物，已成为治疗外周动脉疾病的一种新的血管内治疗方法。在这项研究中，我们评估了角化糖（KOS）作为一种新的dcb涂层赋形剂的使用，以传递和保留紫杉醇。方法：建立了一种定制涂层方法，将KOS和紫杉醇沉积在未涂层的血管成形术气球上。与市售的DCB相比，采用一种新型的血管运动模拟离体血流模型，在1小时和3天评估了kos -紫杉醇涂层的保留率。此外，在兔髂-股损伤模型中评估了kos -紫杉醇涂层的局部区域生物学反应。结果：与市售DCB相比，KOS涂层在搏动条件下血管运动3天后紫杉醇保留率更高（14.89 +/- 4.12 ng/mg vs. 0.60 +/- 0.26 ng/mg, p = 0.018）。经kos -紫杉醇处理动脉的组织学分析显示，与未涂覆球囊、仅kos球囊和仅紫杉醇球囊相比，新内膜厚度显著减少。结论：增强靶向动脉段的药物传递和滞留能力最终可以改善临床外周血管内预后。
Background: Drug-coated balloons (DCBs), which deliver anti-proliferative drugs with the aid of excipients, have emerged as a new endovascular therapy for the treatment of peripheral arterial disease. In this study, we evaluated the use of keratose (KOS) as a novel DCB-coating excipient to deliver and retain paclitaxel. Methods: A custom coating method was developed to deposit KOS and paclitaxel on uncoated angioplasty balloons. The retention of the KOS-paclitaxel coating, in comparison to a commercially available DCB, was evaluated using a novel vascular-motion simulating ex vivo flow model at 1 h and 3 days. Additionally, the locoregional biological response of the KOS-paclitaxel coating was evaluated in a rabbit ilio-femoral injury model at 14 days. Results: The KOS coating exhibited greater retention of the paclitaxel at 3 days under pulsatile conditions with vascular motion as compared to the commercially available DCB (14.89 +/- 4.12 ng/mg vs. 0.60 +/- 0.26 ng/mg, p = 0.018). Histological analysis of the KOS-paclitaxel-treated arteries demonstrated a significant reduction in neointimal thickness as compared to the uncoated balloons, KOS-only balloon and paclitaxel-only balloon. Conclusions: The ability to enhance drug delivery and retention in targeted arterial segments can ultimately improve clinical peripheral endovascular outcomes.