Synthesis of Ionizable Lipids for Gene Delivery to the Lung Using an Ugi Four Component Reaction

The development of efficient delivery systems for therapeutic agents with organ-specific targeting is critical for advancing targeted therapies for effective treatment. In this study, we present a novel approach utilizing a four-component reaction for the synthesis of a diverse library of lipids. These lipids exhibit a distinctive and remarkable tropism toward the lung, with a supplementary affinity toward the spleen. This work showcases the potential of this versatile synthetic strategy in tailoring lipid structures for enhanced organ-specific targeting, opening new avenues for the precise delivery of therapeutic payloads to specific tissues of interest. These findings hold significant promise for the development of advanced therapeutic interventions for pulmonary disorders.