Fine-tuning the Structure and Properties of Lipid Nanoparticles with Microfluidics

Luca Casettari – Professor, Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino 61029, Italy; Sara Elsafy – Doctoral student, Institute of Experimental Molecular Imaging, RWTH Aachen University; Fabian Kiessling – Professor, Institute of Experimental Molecular Imaging, RWTH Aachen University; Twan Lammers – Professor, Institute of Experimental Molecular Imaging, RWTH Aachen University; Josbert Metselaar – Group Leader, Institute of Experimental Molecular Imaging, RWTH Aachen University; Roger Pallares – Group Leader, Institute of Experimental Molecular Imaging, RWTH Aachen University; Mattia Tiboni – Researcher, Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino 61029, Italy

Introduction:

Lipid nanoparticles (LNP) are widely used for nucleic acid delivery, with size, composition, and internal morphology recognized as key determinants of stability, biodistribution and transfection efficiency [1]. While microfluidic (MF) synthesis enables precise control of size and polydispersity (PDI), LNP with similar bulk properties can exhibit strikingly different internal structures [2]. Conventional size-based characterization does not capture these differences, highlighting the need for rapid, morphology-sensitive techniques for controlled MF production and predictable in vivo performance.