TY - JOUR
T1 - Do we really understand how drug eluted from stents modulates arterial healing?
AU - McQueen, Alistair
AU - Escuer, Javier
AU - Aggarwal, Ankush
AU - Kennedy, Simon
AU - McCormick, Christopher
AU - Oldroyd, Keith
AU - McGinty, Sean
PY - 2021/5/15
Y1 - 2021/5/15
N2 - 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.
AB - 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.
KW - cell proliferation
KW - drug-eluting stents
KW - ligand-receptor interactions
KW - mathematical modelling
KW - pharmacodynamics
KW - smooth muscle cells
UR - http://www.scopus.com/inward/record.url?scp=85104907782&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2021.120575
DO - 10.1016/j.ijpharm.2021.120575
M3 - Article
C2 - 33845150
AN - SCOPUS:85104907782
VL - 601
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 120575
ER -