Combining mathematical modelling with in vitro experiments to predict in vivo drug-eluting stent performance

McKittrick, C., McKee, S., Kennedy, S., Oldroyd, K., Wheel, M., Pontrelli, G., Dixon, S., Mcginty, S. and McCormick, C. (2019) Combining mathematical modelling with in vitro experiments to predict in vivo drug-eluting stent performance. Journal of Controlled Release, 303, pp. 151-161. (doi:10.1016/j.jconrel.2019.03.012) (PMID:30878363)

McKittrick, C., McKee, S., Kennedy, S., Oldroyd, K., Wheel, M., Pontrelli, G., Dixon, S., Mcginty, S. and McCormick, C. (2019) Combining mathematical modelling with in vitro experiments to predict in vivo drug-eluting stent performance. Journal of Controlled Release, 303, pp. 151-161. (doi:10.1016/j.jconrel.2019.03.012) (PMID:30878363)

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Abstract

In this study, we developed a predictive model of in vivo stent based drug release and distribution that is capable of providing useful insights into performance. In a combined mathematical modelling and experimental approach, we created two novel sirolimus-eluting stent coatings with quite distinct doses and release kinetics. Using readily measurable in vitro data, we then generated parameterised mathematical models of drug release. These were then used to simulate in vivo drug uptake and retention. Finally, we validated our model predictions against data on drug kinetics and efficacy obtained in a small in vivo evaluation. In agreement with the in vivo experimental results, our mathematical model predicted consistently higher sirolimus content in tissue for the higher dose stents compared with the lower dose stents. High dose stents resulted in statistically significant improvements in three key efficacy measures, providing further evidence of a basic relationship between dose and efficacy within DES. However, our mathematical modelling suggests a more complex relationship is at play, with efficacy being dependent not only on delivering an initial dose of drug sufficient to achieve receptor saturation, but also on the consequent drug release rate being tuned to ensure prolonged saturation. In summary, we have demonstrated that our combined in vitro experimental and mathematical modelling framework may be used to predict in vivo DES performance, opening up the possibility of an in silico approach to optimising the drug release profile and ultimately the effectiveness of the device.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mcginty, Dr Sean and Kennedy, Dr Simon and Oldroyd, Dr Keith
Authors: McKittrick, C., McKee, S., Kennedy, S., Oldroyd, K., Wheel, M., Pontrelli, G., Dixon, S., Mcginty, S., and McCormick, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Science and Engineering > School of Engineering > Biomedical Engineering
Journal Name:Journal of Controlled Release
Publisher:Elsevier
ISSN:0168-3659
ISSN (Online):1873-4995
Published Online:13 March 2019
Copyright Holders:Copyright © 2019 Elsevier
First Published:First published in Journal of Controlled Release 303:151-161
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
579501Optimal Design of Drug Eluting StentsSimon KennedyEngineering and Physical Sciences Research Council (EPSRC)EP/J007579/1RI CARDIOVASCULAR & MEDICAL SCIENCES