Dresden 2026 – scientific programme
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CPP: Fachverband Chemische Physik und Polymerphysik
CPP 43: Biomaterials and Biopolymers (joint session BP/CPP)
CPP 43.4: Talk
Thursday, March 12, 2026, 10:15–10:30, BAR/SCHÖ
pH-dependent phase transitions in ionizable lipid mesophases — •Ekaterina Kostyurina1, Susanne Liese2, Akhil Sudarsan2, Julian Philipp1, and Joachim Rädler1 — 1Faculty of Physics, Ludwig-Maximilians University, 80539 Munich, Germany — 2Faculty of Mathematics, Natural Science, and Materials Engineering, Institute of Physics, University of Augsburg, 86159 Augsburg, Germany
Lipid Nanoparticles (LNPs) have proven valuable in modern medicine as a medium for RNA delivery. Nanoparticles containing cationic ionizable lipid (CIL), cholesterol and structural lipids complex with nucleic acids into size-controlled particles that transport nucleic acid molecules across cell membranes via the endocytic uptake pathway. The delivery efficiency of a drug or vaccine is directly related to the efficiency of the endosomal release. Here, we study pH-dependent structural transitions of the CIL core phase which are believed to play an essential role in this process. We use bulk phases of ionizable lipid/cholesterol as a model system of the LNP core which allows us to study the structure of the lipid phases with high precision using X-ray diffraction. We show that the commonly used ionizable lipids overcome the inverted micellar-inverted hexagonal phase transition within the pH range typical for endosomal life cycle, and connect structural properties of the phases with LNP efficacy. Furthermore, we are aiming to understand the thermodynamics of these phase transitions by combining experimental measurements with theoretical modeling. This will help to better understand the structure-activity relation of LNPs and to increase the delivery efficiency in clinically relevant LNP delivery systems.
Keywords: Lipid nanoparticles; ionizable lipids; lipid mesophases; SAXS