Design, Development, In Vitro and Preliminary In Vivo Evaluation of a Novel Photo-Angioplasty Device: Lumi-Solve.
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.
['Liu|HongBin|H|', 'Sama|Gopal R|GR|', 'Robinson|Andrea|A|', 'Mountford|Simon|S|', 'E Thompson|Philip|P|', 'Rodda|Andrew|A|', 'Forsythe|John|J|', 'Mornane|Patrick J|PJ|', 'Pasic|Paul|P|', 'Thissen|Helmut|H|', 'Byrne|Melissa|M|', 'Kaye|David M|DM|', 'Dear|Anthony E|AE|http://orcid.org/0000-0001-7832-2294']
D017130:Angioplasty D000818:Animals D017536:Carotid Artery, Common D006965:Hyperplasia D058426:Neointima D017239:Paclitaxel D012756:Sheep
Photo-angioplasty Drug eluting balloon catheter Neointimal hyperplasia Epigenetics