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

HongBin Liu, Gopal R. Sama, Andrea Robinson, Simon Mountford, Philip E. Thompson, Andrew Rodda, John Forsythe, Patrick J. Mornane, Paul Pasic, Helmut Thissen, Melissa Byrne, David M. Kaye, Anthony E. Dear

Research output: Contribution to journalArticleResearchpeer-review

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-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.

Original languageEnglish
Pages (from-to)466–473
Number of pages8
JournalCardiovascular Engineering and Technology
Volume12
DOIs
Publication statusPublished - Aug 2021

Keywords

  • Drug eluting balloon catheter
  • Epigenetics
  • Neointimal hyperplasia
  • Photo-angioplasty

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