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

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Data availability

All data generated or analyzed during this study are included in this manuscript and its supplementary information files.

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Acknowledgments

Dr Gopal Reddy Sama: Monash Graduate Scholarship, Monash International Postgraduate Research Scholarship, Dean’s Postgraduate Research Scholarship and Dean’s International Postgraduate Research Scholarship. Medtronic Australasia Pty and Abbott Australasia Pty Ltd: Provision of PABA. Nathaniel Sperka: Prizmatix Ltd, Israel: Advice and provision of fibre-optics. Roland Bays: Medlight SA, Switzerland: Advice and provision of fibre-optics.

Funding

The study was supported, in part, by the Eastern Health Foundation, Robert C Bulley Surgical Research Grant. The Eastern Health Foundation had no role in the design of the study, collection, analysis, and interpretation of data or in writing the manuscript.

Author information

Author notes

  1. HongBin Liu and Gopal R. Sama are equal first author.

Authors and Affiliations

  1. Eastern Health Clinical School, Monash University, Box Hill, Australia

    HongBin Liu & Anthony E. Dear

  2. Department of Chemistry, Monash University, Clayton, Australia

    Gopal R. Sama & Andrea Robinson

  3. Monash Institute of Pharmaceutical Sciences, Monash University, Clayton, Australia

    Simon Mountford & Philip E. Thompson

  4. Monash Institute of Medical Engineering, Monash University, Clayton, Australia

    Andrew Rodda & John Forsythe

  5. School of Chemistry, University of Melbourne, Melbourne, Australia

    Patrick J. Mornane

  6. CSIRO Biomedical Translational Facility, Melbourne, Australia

    Paul Pasic & Helmut Thissen

  7. Baker Heart and Diabetes Institute, Melbourne, Australia

    Melissa Byrne & David M. Kaye

Authors
  1. HongBin Liu
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  2. Gopal R. Sama
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Corresponding author

Correspondence to Anthony E. Dear.

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Conflict of interest

Authors HongBin Liu, Gopal Sama, Simon Mountford, Philip E. Thompson, Andrew Rodda, John Forsythe, Helmut Thissen, Melissa Byrne, David M Kaye and Anthony E Dear are named as inventors on International Patent Application PCT/AU2020/050009 filed on behalf of Monash University, Baker Heart and Diabetes Institute and the Commonwealth Scientific and Industrial Research Organisation which, in part, relates to work presented in this manuscript.

Ethics approval

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees. All procedures performed in studies involving animals were in accordance with the ethical standards of the Baker Heart and Diabetes Institute Animal Ethics Committee, Melbourne, Australia, Approval number 1513767.1.

Additional information

Associate Editor James E. Moore oversaw the review of this article.

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Liu, H., Sama, G.R., Robinson, A. et al. Design, Development, In Vitro and Preliminary In Vivo Evaluation of a Novel Photo-Angioplasty Device: Lumi-Solve. Cardiovasc Eng Tech 12, 466–473 (2021). https://doi.org/10.1007/s13239-021-00525-y

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  • DOI: https://doi.org/10.1007/s13239-021-00525-y

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