Do we really understand how drug eluted from stents modulates arterial healing?

McQueen, A., Escuer, J., Aggarwal, A. , Kennedy, S. , McCormick, C., Oldroyd, K. and Mcginty, S. (2021) Do we really understand how drug eluted from stents modulates arterial healing? International Journal of Pharmaceutics, 601, 120575. (doi: 10.1016/j.ijpharm.2021.120575) (PMID:33845150)

Abstract

The advent of drug-eluting stents (DES) has revolutionised the treatment of coronary artery disease. These devices, coated with anti-proliferative drugs, are deployed into stenosed or occluded vessels, compressing the plaque to restore natural blood flow, whilst simultaneously combating the evolution of restenotic tissue. Since the development of the first stent, extensive research has investigated how further advancements in stent technology can improve patient outcome. Mathematical and computational modelling has featured heavily, with models focussing on structural mechanics, computational fluid dynamics, drug elution kinetics and subsequent binding within the arterial wall; often considered separately. Smooth Muscle Cell (SMC) proliferation and neointimal growth are key features of the healing process following stent deployment. However, models which depict the action of drug on these processes are lacking. In this article, we start by reviewing current models of cell growth, which predominantly emanate from cancer research, and available published data on SMC proliferation, before presenting a series of mathematical models of varying complexity to detail the action of drug on SMC growth in vitro. Our results highlight that, at least for Sodium Salicylate and Paclitaxel, the current state-of-the-art nonlinear saturable binding model is incapable of capturing the proliferative response of SMCs across a range of drug doses and exposure times. Our findings potentially have important implications on the interpretation of current computational models and their future use to optimise and control drug release from DES and drug-coated balloons.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McQueen, Mr Alistair and Mcginty, Dr Sean and Aggarwal, Dr Ankush and Kennedy, Professor Simon and Oldroyd, Dr Keith and Escuer Gracia, Javier
• Authors: McQueen, A., Escuer, J., Aggarwal, A., Kennedy, S., McCormick, C., Oldroyd, K., and Mcginty, S.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Science and Engineering > School of Engineering > Biomedical Engineering; College of Science and Engineering > School of Engineering > Infrastructure and Environment
• Journal Name: International Journal of Pharmaceutics
• Publisher: Elsevier
• ISSN: 0378-5173
• ISSN (Online): 1873-3476
• Published Online: 09 April 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in International Journal of Pharmaceutics 601: 102575
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
303232		EPSRC Centre for Multiscale soft tissue mechanics with MIT and POLIMI (SofTMech-MP)	Xiaoyu Luo	Engineering and Physical Sciences Research Council (EPSRC)	EP/S030875/1	M&S - Mathematics