Prediction and Validation of Diffusion Coefficients in a Model Drug Delivery System

Diffusion of drug and solvent in polymer-based drug delivery systems is of central significance to controlled drug delivery, as well as to the potential for unintended leaching from or uptake into implantable medical devices. Knowledge of diffusion rates is thus essential for the development of controlled drug delivery systems and to regulation of medical devices for which chemical leaching presents a potential health concern. However, obtaining accurate values for diffusion constants for such systems under physiologically relevant conditions, in particular at non-elevated temperatures, represents a formidable challenge, both experimentally and computationally. We present fully atomistic molecular dynamics simulation predictions of diffusion coefficients in a model drug delivery system (a non-resorbable polymeric drug-eluting stent coating), that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. In addition, using a coarse-grained molecular dynamics model, we simulate microstructure formation of implantable block copolymer coatings under various processing conditions to better understand the complex molecular behaviors that dictate microstructural orientation and subsequent drug release rates. Finally, we look ahead to how diffusion may be calculated more rapidly by employing a simulation approach informed by knowledge from the closely related field of glass physics.