Molecular dynamics simulations uncover drying-induced lipid nanoparticle–excipient interactions.

Introduction: While RNA therapeutics are theoretically well-suited for treating pulmonary disorders via localized lung administration, this presents significant technical challenges in practice [1]. In response, we have proposed inhalable dry powder formulations of RNA-loaded lipid nanoparticles (LNPs) [2]. These formulations can be delivered to the lungs using well-established dry powder inhalers. The process of converting LNPs into dry powder formulations, however, induces structural changes. Here, we combined computational and experimental approaches, to provide insights into LNP behavior post-drying.