Eastern Health Clinical School, Monash University, Box Hill, Australia.
Department of Chemistry, Monash University, Clayton, Australia.
Cardiovasc Eng Technol. 2021 Aug;12(4):466-473. doi: 10.1007/s13239-021-00525-y. Epub 2021 Mar 11.
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.
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.
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.
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.
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）与安全性问题相关。替代涂层剂和靶向递送系统可能会提高安全性和 DEBc 的疗效。我们利用设计、开发和评估的多平台方法，设计并评估了一种新型的 DEBc，其表面涂有经紫外线（UV）365nm 激活的笼状米托蒽醌-3（c-MCT-3），这是一种组蛋白去乙酰化酶抑制剂（HDACi）类别的表观遗传药物。
通过光谱法评估体外导管和对比介质对 UV365nm 的传输。通过色谱法评估 c-MCT-3 向 MCT-3 的 UV365nm 转化。评估 c-MCT-3±UV365nm 的细胞毒性和 HDACi 活性。在羊颈动脉模型中评估体内 c-MCT-3 向 MCT-3 的 UV365nm 转化。
导管材料和稀释对比介质不会减弱 UV365nm 的传输或 c-MCT-3 的激活。c-MCT-3 的细胞毒性比 MCT-3 和 PTX 小。UV365nm 激活的 c-MCT-3 具有 HDACi 活性。体内激活 c-MCT-3 可产生 MCT-3。
利用化学、光纤和导管为基础的技术平台组合开发的新型 DEBc 设备 Lumi-Solve，具有将生物活性 HDACi 靶向递送至血管壁的潜力，支持直接应用于 NIH 的管理，值得进一步进行体内研究。
