Poster H11 - Dual action drug coated balloons to reduce neointimal hyperplasia while promoting healing by faster endothelialization

Thursday, October 24, 2024

2:45 PM – 3:45 PM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Sreekiran Nataraj

Jun Lab Research Assistant
University of Alabama at Birmingham
Hoover, Alabama, United States

Co-Author(s)

Robbie J. Cross, Jr. (he/him/his)

Graduate Student
University of Alabama at Birmingham, Alabama, United States
JS

Jennifer Sherwood

Director of Research and Development
Endomimetics, United States

Primary Investigator(s)

Ho-Wook Jun, PhD

Professor
University of Alabama at Birmingham
Birmingham, Alabama, United States

Introduction: Cardiovascular disease (CVD) is the leading cause of death. CVD presents itself as lesions in the artery wall, commonly treated by stenting. However, in femoropopliteal peripheral artery disease (PAD), stenting has a considerable risk of stent fracture resulting in restenosis and total stent occlusion. Uncoated and drug-coated balloon (DCB) angioplasty trumps stenting to avoid potential complications. Plain old balloon angioplasty is proven insufficient as up to 60% of patients suffer from restenosis and recurrence of symptoms. DCB are treated with anti-proliferative agents to prevent restenosis. Commonly, clinical usage of DCB utilizes paclitaxel as the drug of choice. However, recent research has exposed paclitaxel to have an increased risk of death. The –limus (sirolimus, everolimus) family of drugs is an attractive option as a replacement drug for paclitaxel based off its success in drug-eluting stents (DES) and safety over paclitaxel. Sirolimus has been shown to be effective in suppressing restenosis and neointimal hyperplasia (NIH) but delays re-reendothelialization. Delayed re-endothelialization can lead to thrombosis, inflammation, and restenosis. To address these challenges, we propose a dual-action DCB coating consisting of NO-releasing peptide amphiphiles (PA) to enhance re-endothelialization and low-dose sirolimus releasing liposomes to quickly suppress NIH and restenosis.

Materials and

Methods: The bionanomatrix is composed of nitric oxide (NO)-releasing bionanomatrix and sirolimus encapsulated liposomes. These components are essential for recruiting endothelial cells (ECs) while suppressing smooth muscle cell (SMCs) proliferation respectively. Varying concentrations of sirolimus and NO’s effect on cell proliferation were assessed in vitro on SMCs and ECs via PCNA. For the ex vivo study, the bionanomatrix was coated onto the DCB and expanded into a porcine coronary artery vessel wall to measure drug transfer and retention. These pig arteries were subjected to physiological flow conditions via a peristaltic pump.

Results, Conclusions, and Discussions: In vitro, NO-release significantly increased EC proliferation while sirolimus significantly decreased SMC proliferation. NO-release paired with sirolimus decreased SMC proliferation while increasing EC proliferation. Ex vivo, DCB deployment transferred around 30% of the bionanomatrix to the vessel wall.
The bionanomatrix coated DCB can effectively transfer bionanomatrix while promoting re-endothelialization and suppressing NIH.

Acknowledgements (Optional):