title: Combining gas-phase electrophoretic mobility molecular analysis (GEMMA), light scattering, field flow fractionation and cryo electron microscopy in a multidimensional approach to characterize liposomal carrier vesicles.
abstract: For drug delivery, characterization of liposomes regarding size, particle number concentrations, occurrence of low-sized liposome artefacts and drug encapsulation are of importance to understand their pharmacodynamic properties. In our study, we aimed to demonstrate the applicability of nano Electrospray Gas-Phase Electrophoretic Mobility Molecular Analyser (nES GEMMA) as a suitable technique for analyzing these parameters. We measured number-based particle concentrations, identified differences in size between nominally identical liposomal samples, and detected the presence of low-diameter material which yielded bimodal particle size distributions. Subsequently, we compared these findings to dynamic light scattering (DLS) data and results from light scattering experiments coupled to Asymmetric Flow-Field Flow Fractionation (AF4), the latter improving the detectability of smaller particles in polydisperse samples due to a size separation step prior detection. However, the bimodal size distribution could not be detected due to method inherent limitations. In contrast, cryo transmission electron microscopy corroborated nES GEMMA results. Hence, gas-phase electrophoresis proved to be a versatile tool for liposome characterization as it could analyze both vesicle size and size distribution. Finally, a correlation of nES GEMMA results with cell viability experiments was carried out to demonstrate the importance of liposome batch-to-batch control as low-sized sample components possibly impact cell viability.
authors.affiliation: Department of Surgery, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Carlos
authors.initials: C
authors.lastname: Urey
authors.affiliation: Institute of Chemical Technologies and Analytics, TU Wien, Vienna, Austria.
authors.forename: Victor U
authors.initials: VU
authors.lastname: Weiss
authors.affiliation: Department of Environmental Geosciences and Environmental Science Research Network, University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gondikas
authors.affiliation: Department of Environmental Geosciences and Environmental Science Research Network, University of Vienna, Vienna, Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: von der Kammer
authors.affiliation: Department of Environmental Geosciences and Environmental Science Research Network, University of Vienna, Vienna, Austria.
authors.forename: Thilo
authors.initials: T
authors.lastname: Hofmann
authors.affiliation: Institute of Chemical Technologies and Analytics, TU Wien, Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Marchetti-Deschmann
authors.affiliation: Institute of Chemical Technologies and Analytics, TU Wien, Vienna, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Allmaier
authors.affiliation: Clinical Protein Science & Imaging, Department of Biomedical Engineering, Lund University, Lund, Sweden.
authors.forename: György
authors.initials: G
authors.lastname: Marko-Varga
authors.affiliation: Department of Surgery, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D020285:Cryoelectron Microscopy; D000067493:Dynamic Light Scattering; D004586:Electrophoresis; D031521:Fractionation, Field Flow; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D002784:Cholesterol
keywords: Cytotoxicity; Dynamic light scattering; Flow field flow fractionation; Gas-phase electrophoretic mobility molecular analysis; Liposome; Transmission electron microscopy