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

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• 作者：Carlos Urey^a ; ¹ ; Victor U. Weiss^b ; ¹ ; Andreas Gondikas^c ; Frank von der Kammer^c ; Thilo Hofmann^c ; Martina Marchetti-Deschmann^b ; Gü ; nter Allmaier^b ; Gyö ; rgy Marko-Varga^d ; Roland Andersson^a ; ^{roland.andersson@med.lu.se" class="auth_mail" title="E-mail the corresponding author} ; ^{roland.andersson@skane.se" class="auth_mail" title="E-mail the corresponding author}
• 关键词：AF4 ; Asymmetric Flow-Field Flow Fractionation ; CPC ; Condensation Particle Counter ; DLS ; Dynamic Light Scattering ; EM ; Electrophoretic Mobility ; GEMMA ; Gas-phase Electrophoretic Mobility Molecular Analysis ; nDMA ; nano Differential Mobility Analyzer ; nES ; nano Electrospray ; PDI ; Polydispersity Index ; PEG ; Polyethylene Glycol ; SEC ; Size Exclusion Chromatography ; SLS ; Static Light Scattering ; TEM ; Transmission Electron Microscopy
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：20 November 2016
• 年：2016
• 卷：513
• 期：1-2
• 页码：309-318
• 全文大小：1619 K

文摘

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.