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

Craig M. McKittrick, Sean McKee, Simon Kennedy, Keith Oldroyd, Marcus Wheel, Giuseppe Pontrelli, Simon Dixon, Sean McGinty, Christopher McCormick

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.
LanguageEnglish
Pages151-161
Number of pages11
JournalJournal of Controlled Release
Volume303
Early online date13 Mar 2019
DOIs
Publication statusPublished - 10 Jun 2019

Fingerprint

Drug-Eluting Stents
Stents
Sirolimus
Theoretical Models
Pharmaceutical Preparations
Computer Simulation
Pharmacokinetics
In Vitro Techniques
Equipment and Supplies
Drug Liberation

Keywords

  • drug-eluting stents
  • mathematical model
  • in vivo evaluation

Cite this

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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.",
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Combining mathematical modelling with in vitro experiments to predict in vivo drug-eluting stent performance. / McKittrick, Craig M.; McKee, Sean; Kennedy, Simon; Oldroyd, Keith; Wheel, Marcus; Pontrelli, Giuseppe; Dixon, Simon; McGinty, Sean; McCormick, Christopher.

In: Journal of Controlled Release, Vol. 303, 10.06.2019, p. 151-161.

Research output: Contribution to journalArticle

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