Dresden 2026 – scientific programme

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BP: Fachverband Biologische Physik

BP 16: Membranes, Vesicles and Synthetic Life-like Systems II

BP 16.11: Talk

Wednesday, March 11, 2026, 12:30–12:45, BAR/0205

pH Dependence of the Structure of Drug-Free Lipid Nanoparticle Dispersions — •Marta Gallo¹, Klaus Götz¹, Bishoy Hakim¹, Carola Vogel¹, Christian Bär¹, Lionel Porcar², and Tobias Unruh¹ — ¹Institute for Crystallography and Structural Physics, Friedrich Alexander University Erlangen Nürnberg — ²Institut Laue-Langevin, 71 Avenue des Martyrs, Grenoble 38042, France

Lipid nanoparticle (LNP) dispersions are promising drug-delivery systems due to their ability to encapsulate diverse therapeutics and release them in controlled ways. A key advantage of many LNPs is their sensitivity to environmental pH, enabling drug release in acidic endosomal conditions through lipid conformational changes that destabilize the particles. To clarify these mechanisms, we synthesized drug-free LNPs mimicking the Comirnaty formulation and examined how pH affects their structure. Using simultaneous small angle X-ray and neutron scattering (SAXS/SANS) at the ILL D22 instrument, we monitored particle swelling and ordered-structure formation across different pH levels. Dialysis experiments, transitioning samples between pH 3.3 and 7, demonstrated fully reversible structural changes, as confirmed by cryo-TEM. Coupling SAXS/SANS with photon correlation spectroscopy (PCS) revealed a complex particle size distribution and deeper insight into LNP dynamics under different contrasts and pH conditions. The results clarify how pH-triggered structural transitions govern LNP behavior, supporting the design of next-generation delivery systems with enhanced release control and targeting.

Keywords: LNPs; drug-delivery; pH; dialysis; SAXS/SANS/PCS