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)

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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
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
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

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303232EPSRC Centre for Multiscale soft tissue mechanics with MIT and POLIMI (SofTMech-MP)Xiaoyu LuoEngineering and Physical Sciences Research Council (EPSRC)EP/S030875/1M&S - Mathematics