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

McKittrick CM, Kennedy S, Oldroyd KG, McGinty S, McCormick C - Ann Biomed Eng (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, University of Strathclyde, Glasgow, UK.

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.

No MeSH data available.


Related in: MedlinePlus

Partition coefficients of everolimus (blue), paclitaxel (red) and sirolimus (green) in atherosclerotic human aorta. Partition coefficient was greatest in the medial layer (left) where lipid content was lowest, whilst it was lowest in the intimal layer (right) where lipid content was most abundant. These data were obtained from a single sample dissected into three tunic layers, cut into 12 sections, and immersed in drug solution for 96 h (n = 3 for each layer and drug). Figure adapted from Tzafriri et al. 2010.63
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Fig3: Partition coefficients of everolimus (blue), paclitaxel (red) and sirolimus (green) in atherosclerotic human aorta. Partition coefficient was greatest in the medial layer (left) where lipid content was lowest, whilst it was lowest in the intimal layer (right) where lipid content was most abundant. These data were obtained from a single sample dissected into three tunic layers, cut into 12 sections, and immersed in drug solution for 96 h (n = 3 for each layer and drug). Figure adapted from Tzafriri et al. 2010.63

Mentions: Examination of tissue ex vivo has been shown to be particularly useful in determining the impact of tissue components and physiological transport mechanisms on drug release and distribution following stenting. Building on the models described earlier,9,23 Tzafriri et al.63 used a variety of excised vessels containing plaque to investigate the extent to which various components of disease, including alterations in tissue composition and drug-specific receptor distributions, impact upon drug transport. Samples of human aorta were obtained post-mortem from four donors and all had some degree of necrotic and calcific regions within plaques, which also contained moderate to high levels of lipid. Partition coefficients for sirolimus, paclitaxel and everolimus were evaluated in a lightly calcified sample, which was separated into its tunic layers and immersed in solutions of the drugs for 96 h. Within all three layers drug deposition was dependent on lipid content (see Fig. 3). To further validate these findings the authors calculated the partition coefficient of the medial layer of healthy calf carotid arteries which had lower lipid content than the human samples, and subsequently the partition coefficient was higher. Overall these findings were contrary to the previously held expectation that hydrophobic drugs would be better retained in a lipid rich environment.15,37Figure 3


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

McKittrick CM, Kennedy S, Oldroyd KG, McGinty S, McCormick C - Ann Biomed Eng (2015)

Partition coefficients of everolimus (blue), paclitaxel (red) and sirolimus (green) in atherosclerotic human aorta. Partition coefficient was greatest in the medial layer (left) where lipid content was lowest, whilst it was lowest in the intimal layer (right) where lipid content was most abundant. These data were obtained from a single sample dissected into three tunic layers, cut into 12 sections, and immersed in drug solution for 96 h (n = 3 for each layer and drug). Figure adapted from Tzafriri et al. 2010.63
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4764635&req=5

Fig3: Partition coefficients of everolimus (blue), paclitaxel (red) and sirolimus (green) in atherosclerotic human aorta. Partition coefficient was greatest in the medial layer (left) where lipid content was lowest, whilst it was lowest in the intimal layer (right) where lipid content was most abundant. These data were obtained from a single sample dissected into three tunic layers, cut into 12 sections, and immersed in drug solution for 96 h (n = 3 for each layer and drug). Figure adapted from Tzafriri et al. 2010.63
Mentions: Examination of tissue ex vivo has been shown to be particularly useful in determining the impact of tissue components and physiological transport mechanisms on drug release and distribution following stenting. Building on the models described earlier,9,23 Tzafriri et al.63 used a variety of excised vessels containing plaque to investigate the extent to which various components of disease, including alterations in tissue composition and drug-specific receptor distributions, impact upon drug transport. Samples of human aorta were obtained post-mortem from four donors and all had some degree of necrotic and calcific regions within plaques, which also contained moderate to high levels of lipid. Partition coefficients for sirolimus, paclitaxel and everolimus were evaluated in a lightly calcified sample, which was separated into its tunic layers and immersed in solutions of the drugs for 96 h. Within all three layers drug deposition was dependent on lipid content (see Fig. 3). To further validate these findings the authors calculated the partition coefficient of the medial layer of healthy calf carotid arteries which had lower lipid content than the human samples, and subsequently the partition coefficient was higher. Overall these findings were contrary to the previously held expectation that hydrophobic drugs would be better retained in a lipid rich environment.15,37Figure 3

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, University of Strathclyde, Glasgow, UK.

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.

No MeSH data available.


Related in: MedlinePlus