Prediction and Validation of Diffusion Coefficients in a Model Drug Delivery System Using Microsecond Atomistic Molecular Dynamics Simulation and Vapor Sorption Analysis
Christopher Forrey, D M. Saylor, Joshua S. Silverstein, Jack F. Douglas, Eric Davis, Yossef A. Elabd
Diffusion of small to medium sized molecules in polymeric medical device materials underlies a broad range of public health concerns related to unintended leaching from or uptake into implantable medical devices. Knowledge of diffusion rates is thus essential to bringing safe and effective devices to the market more efficiently. However, obtaining accurate diffusion coefficients for such systems at physiological temperature represents a formida-ble challenge, both experimentally and computationally. While molecular dynamics simulation has been used to accu-rately predict the diffusion coefficients, D, of a handful of gases in various polymers, this success has not been extend-ed to molecules larger than gases, e.g., condensable vapors, liquids, drugs. We present atomistic molecular dynamics simulation predictions of diffusion in a model drug eluting system that represent a dramatic improvement in accuracy compared to previous simulation predictions for comparable systems. We find that accurate predictions are limited largely by the treatment of system dynamics. In particular, we show that, for simulations of insufficient duration, sub-diffusive dynamics leads to dramatic over-prediction of D. We present useful metrics for monitoring the extent of sub-diffusive dynamics and explore how these metrics correlate to error in D. Our work provides important precedent and essential insights for utilizing atomistic molecular dynamics simulations to predict diffusion coefficients of small to medium sized molecules in condensed soft matter systems.
Diffusion, molecular dynamics simulation, medical device, controlled drug release, leaching, glassy dynamics
, Saylor, D.
, Silverstein, J.
, Douglas, J.
, Davis, E.
and Elabd, Y.
Prediction and Validation of Diffusion Coefficients in a Model Drug Delivery System Using Microsecond Atomistic Molecular Dynamics Simulation and Vapor Sorption Analysis, Soft Matter
(Accessed September 30, 2023)