On the influence of non-uniform binding site density in determining arterial drug distribution following stent-based delivery

Escuer, Javier and Scullion, Bryan and McCormick, Christopher and McGinty, Sean (2018) On the influence of non-uniform binding site density in determining arterial drug distribution following stent-based delivery. In: 8th World Congress of Biomechanics, 2018-07-08 - 2018-07-12, Convention Centre Dublin.

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    Abstract

    Many mathematical models have been developed to try to understand drug release from stents and subsequent redistribution in the arterial wall. Models have highlighted the importance of accounting for specific and non-specific binding, concluding that for sirolimus-eluting stents it is more important to sustain release than to increase dose. Modelling has also been used to explain how differences in the binding properties of paclitaxel and sirolimus lead to different retention, suggesting that the optimal delivery strategy is drug-dependent. However, these conclusions have been made based on the assumption that the density of binding sites is uniform across the arterial wall. This is despite experimental evidence to the contrary, suggesting a variation across the wall thickness, with noticeable differences between and within the media and adventitia. Target receptor densities for paclitaxel and sirolimus do not follow the same spatial pattern and when components of disease are present, the picture is further complicated. The aim of this study is therefore to investigate the role of non-uniform binding site density in determining arterial drug distribution following stent-based delivery.