Purpose

Paclitaxel (PTX)-coated drug eluting balloon catheters (DEBc) used in the management of neointimal hyperplasia (NIH) have been associated with safety concerns. Alternative coating agents and targeted delivery systems may improve safety and DEBc efficacy. Utilizing a multi-platform approach we designed, developed and evaluated Lumi-Solve, a novel DEBc, coated with ultraviolet (UV) 365 nm-activated caged metacept-3 (c-MCT-3), an epigenetic agent from the histone deacetylase inhibitor (HDACi) class.

Methods

In vitro catheter and contrast media transmission of UV365nm was evaluated spectroscopically. UV365nm conversion of c-MCT-3 to MCT-3 was evaluated chromatographically. Cellular toxicity and HDACi activity of c-MCT-3 ∓UV365nm was evaluated in vitro. In vivo UV365nm conversion of c-MCT-3 to MCT-3 was evaluated in an ovine carotid artery model.

Results

Catheter material and dilute contrast media did not attenuate UV365nm transmission or c-MCT-3 activation. c-MCT-3 demonstrated less cellular toxicity than MCT-3 and PTX. UV365nm-activated c-MCT-3 demonstrated HDACi activity. In vivo activation of c-MCT-3 produced MCT-3.

Conclusions

Lumi-Solve, a novel DEBc device developed utilizing a combination of chemical, fibre-optic and catheter based technology platforms, demonstrated potential for targeted delivery of bioactive HDACi to the blood vessel wall supporting direct application to the management of NIH and warranting additional in vivo studies.

中文翻译：

---

新型光血管成形术设备的设计、开发、体外和初步体内评估：Lumi - Solve

目的

用于治疗新生内膜增生 (NIH) 的紫杉醇 (PTX) 涂层药物洗脱球囊导管 (DEBc) 存在安全问题。替代涂层剂和靶向递送系统可以提高安全性和 DEBc 功效。利用多平台方法，我们设计、开发和评估了 Lumi-Solve，一种新型 DEBc，涂有紫外线 (UV) 365 nm 激活的笼状 metacept-3 (c-MCT-3)，这是一种来自组蛋白脱乙酰酶抑制剂的表观遗传剂(HDACi) 类。

方法

UV365nm的体外导管和造影剂透射通过光谱法进行评估。c-MCT-3 向 MCT-3 的 UV365nm 转化通过色谱法进行评估。体外评估了c-MCT-3∓UV365nm的细胞毒性和HDACi活性。在绵羊颈动脉模型中评估了 c-MCT-3 到 MCT-3 的体内UV365nm 转化。

结果

导管材料和稀释的造影剂不会减弱 UV365nm 透射或 c-MCT-3 激活。c-MCT-3 表现出比 MCT-3 和 PTX 更小的细胞毒性。UV365nm 激活的 c-MCT-3 显示出 HDACi 活性。c-MCT-3 的体内激活产生了 MCT-3。

结论

Lumi-Solve 是一种结合化学、光纤和导管技术平台开发的新型 DEBc 设备，展示了将生物活性 HDACi 靶向递送到血管壁的潜力，支持直接应用于 NIH 的管理并保证额外的体内学习。