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

Alistair McQueen, Javier Escuer, Ankush Aggarwal, Simon Kennedy, Christopher McCormick, Keith Oldroyd, Sean McGinty

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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.

Original languageEnglish
Article number120575
Number of pages15
JournalInternational Journal of Pharmaceutics
Volume601
Early online date9 Apr 2021
DOIs
Publication statusPublished - 15 May 2021

Keywords

  • cell proliferation
  • drug-eluting stents
  • ligand-receptor interactions
  • mathematical modelling
  • pharmacodynamics
  • smooth muscle cells

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