Gas-phase electrophoresis of single-charged particles enables liposome characterization and finally the resulting vesicle encapsulation capacity determination.

This is the first study indicating a predictive role of MUC4 expression for gemcitabine treatment in the clinical setting.

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.

Abstract. Background Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and devastating disease. In the US and the European countries, PDAC is the fourth leading cause of cancer-related death (1, 2). Incidence and mortality rates follow closely (3, 4) and even though the relative 5-year survival rate has improved slightly over the last years, it is still as low as 7% (2). Surgically removing the primary tumor, i.e. resection, is the only potential cure for PDAC. However, at the time of diagnosis, only around 20% of patients are eligible for surgical resection (5), and even so, most patients will relapse within five years (6). For patients with non-resectable tumors, the main treatment option is chemotherapy which mainly consists of a gemcitabine-based regimen, either alone or in combination with other drugs (7).Mucins belong to a large family of high molecular weight glycoproteins characterized by long tandem repeat regions rich in serine, proline and threonine (8). Mucins are expressed by various epithelial cells (9) while the human mucin family consists of 21 members, MUC1-MUC21. Based on their functions, mucins are further divided into two different subclasses, as either secreted or membrane-bound mucins (10). Secreted mucins can be divided into gelforming (MUC2, MUC5AC, MUC5B, MUC6) and non-gelforming (MUC7) (9). The secreted mucins form a physical barrier of mucous gel for protection of epithelial cells in the respiratory and GI tracts. Membrane-bound mucins (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC13, MUC15, MUC16 and MUC17) are composed of a cytoplasmic tail and a transmembrane region and they contribute to the protective mucous gel through their single extracellular domain of O-glycosylated tandem repeats (8,10).In contrast to a healthy pancreas, which has weak or no mucin expression, pancreatic cancer is characterized by an aberrant expression of multiple mucins. During progression from normal pancreas to a malignant state, expression and glycosylation of both secreted and membrane-bound mucins are altered (10). Furthermore, altered expression of mucins is 6031 This article is freely accessible online.