Software toolkits for in silico screening of polymer excipients used in small molecule formulation and drug delivery.

The use of polymers as excipients in small molecule pharmaceutical formulations is an established approach for the controlled delivery of drugs. However, designing safe and effective formulations is resource-intensive and delays product delivery to the clinic, primarily due to the sensitivity of polymer substructure to delivery properties.

Molecular dynamics (MD) simulations are a powerful in silico tool that can provide detailed insights into the time-dependent behavior of molecular systems at the atomic level. MD can reveal information about the conformational changes, binding interactions, and dynamical properties of molecules. Although MD simulations are associated with high computational demand, increased access to computational power has allowed for the construction of longer and larger simulations. However, limitations remain in the routine application of MD simulations to polymer excipients, such as the difficulty in parameterizing larger polymers and ensuring the transferability of force fields across different polymer chemistries.

In this project, we create a robust and scalable building and parameterization workflow for polymer excipients. This research uses advanced molecular dynamics techniques from organizations such as the Open Force Field Consortium to create a robust in silico polymer parameterization methodology. With our established workflow, we perform systematic molecular dynamics simulations of different polymer:drug systems to yield kinetic and mechanical parameters predicting excipient suitability for drug delivery. This enables fast, accurate, and reproducible profiling of polymers in the context of drug formulation design. We collaborate with experimental formulation development teams at Johnson&Johnson Innovative Medicine to validate our models and drive the design of our polymer:drug candidate systems.

By incorporating existing open-source software, and sharing any resulting tools developed, we aim to promote reproducibility and collaboration throughout the project.