Impact of Lipid Composition and Formulation Parameters on mRNA-LNPs

Sandra Perez Torras, PhD – Principal Investigator, Department of Biochemistry and Molecular Biomedicine, University of Barcelona; Ferran Roig Roig, PhD – R&D Specialist, CDMO, Reig Jofre

Introduction:

Following the success of SARS-CoV-2 mRNA lipid nanoparticles (LNP) vaccines, mRNA-based therapies have emerged as a versatile platform for multiple applications. This work investigates mRNA-LNP formulations using microfluidics and a design of experiments (DoE) approach. Key process parameters (Flow Rate Ratio (FRR) and Nitrogen/Phosphate (N/P) ratio) and lipid composition are varied to obtain nanoparticles with suitable physicochemical properties, including particle size, Polydispersity Index (PdI) and encapsulation efficiency (EE), while also assessing transfection efficiency and cytotoxicity in different cell lines.