Physicochemical characterization of anionic lipid-based ternary siRNA complexes

► Physicochemical properties and biological activity of anionic lipoplexes correlated. ► Physicochemical studies were pivotal in formulation optimization for high silencing. ► Formulation components (lipid, Ca) contributed to serum stability and siRNA loading. ► Structural model of lipoplexes correlated to activity for different formulations. ► Information generated will be useful for product optimization and consistency.