A mesoscale lattice model and atomistic simulations of controlled drug release

Excipients such as polymers are used for the delivery of poorly soluble drugs to enhance drug bioavailability by limiting drug aggregation/crystallization. I will discuss two distinct approaches, which target different time and length scales of the excipient design problem. First, a two-dimensional lattice model is developed of “ants” (drug) performing a random walk in a lattice containing “walls” (excipient). Ants can be “blind” or “friendly”, corresponding to hydrophilic or hydrophobic drug molecules, respectively. Second, atomistic molecular dynamics simulations are performed on an example system containing acrylic acid oligomers as excipient and doxorubicin as the drug. We mimic drug release by matrix swelling in atomistic simulations using a sequential water removal approach that is a crude but simpler alternative of grand canonical ensemble simulations. Drug release by polymer erosion and drug release in a non-swellable, non-eroding matrix is mimicked in our simulations by variations in polymer/drug concentrations. Together, these two simulation approaches provides design rules for choosing polymer-drug combinations for controlled release.