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Design, Development, In Vitro and Preliminary In Vivo Evaluation of a Novel Photo-Angioplasty Device: Lumi-Solve

机译:新型光血管成形术装置的设计、开发、体外和初步体内评估:Lumi-Solve

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Abstract 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-acti-vated 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.
机译:摘要 紫杉醇(PTX)包被药物洗脱球囊导管(DEBc)用于治疗新内膜增生(NIH)与安全性问题有关。替代包衣剂和靶向递送系统可以提高安全性和 DEBc 疗效。利用多平台方法,我们设计、开发和评估了 Lumi-Solve,这是一种新型 DEBc,涂有紫外线 (UV) 365 nm 活性笼式 metacept-3 (c-MCT-3),这是一种来自组蛋白脱乙酰酶抑制剂 (HDACi) 类的表观遗传剂。方法-用光谱法评价UV365nm的体外导管和造影剂透射率。通过色谱法评估 c-MCT-3 向 MCT-3 的 UV365nm 转化率。c-MCT-3的细胞毒性和HDACi活性?UV365nm在体外进行了评估。在绵羊颈动脉模型中评估 c-MCT-3 向 MCT-3 的体内 UV365nm 转化。结果-导管材料和稀释造影剂对UV365nm透射率或c-MCT-3活化没有减弱。c-MCT-3 的细胞毒性低于 MCT-3 和 PTX。UV365nm 激活的 c-MCT-3 显示出 HDACi 活性。体内激活 c-MCT-3 产生 MCT-3。结论-Lumi-Solve 是一种利用化学、光纤和导管技术平台组合开发的新型 DEBc 设备,展示了将生物活性 HDACi 靶向递送至血管壁的潜力,支持直接应用于 NIH 的管理,并值得进行更多的体内研究。

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