Modelling the Impact of Atherosclerosis on Drug Release and Distribution from Coronary Stents

Abstract

Although drug-eluting stents (DES) are now widely used for the treatment of coronary heart disease, there remains considerable scope for the development of enhanced designs which address some of the limitations of existing devices. The drug release profile is a key element governing the overall performance of DES. The use of in vitro, in vivo, ex vivo, in silico and mathematical models has enhanced understanding of the factors which govern drug uptake and distribution from DES. Such work has identified the physical phenomena determining the transport of drug from the stent and through tissue, and has highlighted the importance of stent coatings and drug physical properties to this process. However, there is limited information regarding the precise role that the atherosclerotic lesion has in determining the uptake and distribution of drug. In this review, we start by discussing the various models that have been used in this research area, highlighting the different types of information they can provide. We then go on to describe more recent methods that incorporate the impact of atherosclerotic lesions.

Multiscale Boundary Conditions for Non-Fickian Diffusion Applied to Drug-Eluting Stents

“…When atherosclerosis occurs, a lipid fibrous plaque is formed in the arterial wall due to the accumulation of a high level of low-density lipoprotein (LDL) cholesterol in the lumen and to a series of biochemical reactions that ends with the formation of the atheroma. This lipid accumulation causes the intima to thicken and change its physical properties, which may influence the drug deposition in the arterial wall [26]. In this work, we consider as regions of interest the intima with the presence of a soft lipid plaque and the media, separated by the internal elastic lamina (IEL).…”

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

“…the system of equations (1-2, 4) (with a = r l − L p and b = r l ) and (7)(8)(9)(10)(11)(12) is then closed by allowing the concentration of free drug in the wall to vanish at the periadventitial surface (see e.g [13], [18]):…”

“…Finally, in line with the majority of combined modelling and experimental studies in this field, we have neglected disease in this work. There is growing evidence [11] that disease composition may well have an impact on drug release and subsequent tissue distribution, which calls for the development of more advanced methodologies (both experimental and modelling) to be able to account for this.…”

“…Moreover, such simplified models do not take account of the processes governing uptake of drug into the artery following release from the stent surface. Whilst there are some in vitro and ex vivo approaches that attempt to do this [11], ultimately animal models are still required. The value of in vivo models is that they most closely mimic the clinical situation, with the pig coronary artery being the gold-standard model recommended for pre-clinical evaluation [10].…”

Nanostructured lipid carriers employing polyphenols as promising anticancer agents: Quality by design (QbD) approach

“…Conversely, sustained action is achieved on uniform dispersion of the drug in the lipid matrix. The partition coefficient of the drug and drug release show an inverse relationship (Ittrick et al, 2016). These principles explain how imperative it is to incorporate optimized production parameters in manufacturing of stable NLC systems.…”