Modeling receptor-mediated drug delivery influenced by non-specific binding in stenosed arterial walls with atherosclerotic plaques

Abstract

Background: This study aims to examine how non-specific binding affects drug transfer through receptors in atherosclerotic plaques during stent-based delivery. Hypothesis: We hypothesize that including non-specific binding and saturable receptor interactions in a quantitative model will lead to more accurate predictions of drug distribution and retention in heterogeneous arterial tissues. Materials and Methods: A modeling framework is developed to consider the interactions between dosage, saturable binding, and diffusion, incorporating experimentally determined binding parameters for drug–tissue interactions. Given the diverse nature of the arterial wall—comprising different tissue layers with varying diffusivities—the model integrates drug diffusion, convection, and reaction dynamics within both the plaque and nearby healthy tissue regions. Each tissue layer features free drug, receptor-bound (specific), and non-specifically bound phases, forming a coupled three-phase, two-layer system. The model also accounts for the kinetics of drug-eluting stent (DES) release over time and captures diffusion through the tortuous, porous arterial environment. Results: The simulation results show that key parameters such as dissociation constants and the initial drug load in the stent coating greatly influence drug distribution patterns and retention times across different tissue layers. Conclusion: This model highlights the important role of non-specific binding and tissue heterogeneity in drug retention during stent-based delivery, offering insights that can help optimize drug-eluting stent design and treatment strategies.