Proceedings of the MARESEC 2022

The second European Workshop on Maritime Systems Resilience and Security (MARESEC) was dedicated to the research on Resilience, Security, Technology and related Ethical, Legal, and Social Aspects (ELSA) in the context of Maritime Systems, including but not restricted to (Offshore/Onshore) Infrastructures, Navigation and Shipping and Autonomous Systems. The event, which was organized by the Institute for the Protection of Maritime Infrastructures of the German Aerospace Center (DLR), occurred in a hybrid manner on June, 20th 2022. It counted on 79 participants online and onside at the Fischbahnhof, Bremerhaven, Germany. Out of all submitted extended abstracts, 24 submissions had been selected for presentation. Additionally, 2 works of undergraduate and graduate students have been presented (the final schedule can be found in the appendix). The authors are affiliated to institutions from Canada, Egypt, Finland, Germany, Greece, Norway, Poland, Switzerland, United Kingdom, United States

Effect of matrix-modulating enzymes on the cellular uptake of magnetic nanoparticles and on magnetic hyperthermia treatment of pancreatic cancer models in vivo

Magnetic hyperthermia can cause localized thermal eradication of several solid cancers. However, a localized and homogenous deposition of high concentrations of magnetic nanomaterials into the tumor stroma and tumor cells is mostly required. Poorly responsive cancers such as the pancreatic adenocarcinomas are hallmarked by a rigid stroma and poor perfusion to therapeutics and nanomaterials. Hence, approaches that enhance the infiltration of magnetic nanofluids into the tumor stroma convey potentials to improve thermal tumor therapy. We studied the influence of the matrix-modulating enzymes hyaluronidase and collagenase on the uptake of magnetic nanoparticles by pancreatic cancer cells and 3D spheroids thereof, and the overall impact on magnetic heating and cell death. Furthermore, we validated the effect of hyaluronidase on magnetic hyperthermia treatment of heterotopic pancreatic cancer models in mice. Treatment of cultured cells with the enzymes caused higher uptake of magnetic nanoparticles (MNP) as compared to nontreated cells. For example, hyaluronidase caused a 28% increase in iron deposits per cell. Consequently, the thermal doses (cumulative equivalent minutes at 43 ◦C, CEM43) increased by 15–23% as compared to heat dose achieved for cells treated with magnetic hyperthermia without using enzymes. Likewise, heatinduced cell death increased. In in vivo studies, hyaluronidase-enhanced infiltration and distribution of the nanoparticles in the tumors resulted in moderate heating levels (CEM43 of 128 min as compared to 479 min) and a slower, but persistent decrease in tumor volumes over time after treatment, as compared to comparable treatment without hyaluronidase. The results indicate that hyaluronidase, in particular, improves the infiltration of magnetic nanoparticles into pancreatic cancer models, impacts their thermal treatment and cell depletion, and hence, will contribute immensely in the fight against pancreatic and many other adenocarcinomas

Feasibility of the preparation of cochleate suspensions from naturally derived phosphatidylserines

IntroductionCochleates are cylindrical particles composed of dehydrated phospholipid bilayers. They are typically prepared by addition of calcium ions to vesicles composed of negatively charged phospholipids such as phosphatidylserines (PS). Due to their high physical and chemical stability, they provide an interesting alternative over other lipid-based drug formulations for example to improve oral bioavailability or to obtain a parenteral sustained-release formulation.MethodsIn the present study, the feasibility to prepare cochleate suspensions from soy lecithin-derived phosphatidylserines (SPS) was investigated and compared to the “gold standard” dioleoyl-phosphatidylserine (DOPS) cochleates. The SPS lipids covered a large range of purities between 53 and >96% and computer-controlled mixing was evaluated for the preparation of the cochleate suspensions. Electron microscopic investigations were combined with small-angle x-ray diffraction (SAXD) and Laurdan generalized polarization (GP) analysis to characterize particle structure and lipid organization.ResultsDespite some differences in particle morphology, cochleate suspensions with similar internal lipid structure as DOPS cochleates could be prepared from SPS with high headgroup purity (≥96%). Suspensions prepared from SPS with lower purity still revealed a remarkably high degree of lipid dehydration and well-organized lamellar structure. However, the particle shape was less defined, and the typical cochleate cylinders could only be detected in suspensions prepared with higher amount of calcium ions. Finally, the study proves the feasibility to prepare suspensions of cochleates or cochleate-like particles directly from a calcium salt of soy-PS by dialysis

Formation of liquid crystalline phases in aqueous suspensions of platelet-like tripalmitin nanoparticles

Suspensions of platelet-like shaped tripalmitin nanocrystals stabilized by the pure lecithin DLPC and the lecithin blend S100, respectively, have been studied by small-angle x-ray scattering (SAXS) and optical observation of their birefringence at different tripalmitin (PPP) concentrations φ PPP . It could be demonstrated that the platelets of these potential drug delivery systems start to form a liquid crystalline phase already at pharmaceutically relevant concentrations φ PPP of less than 10 wt. %. The details of this liquid crystalline phase are described here for the first time. As in a previous study [A. Illing et al. , Pharm. Res.21, 592 (2004)] some platelets are found to self-assemble into lamellar stacks above a critical tripalmitin concentration φstPPP of 4 wt. %. In this study another critical concentration φlcPPP≈7 wt. % for DLPC and φlcPPP≈9 wt. % for S100 stabilized dispersions, respectively, has been observed. φlcPPP describes the transition from a phase of randomly oriented stacked lamellae and remaining non-assembled individual platelets to a phase in which the stacks and non-assembled platelets exhibit an overall preferred orientation. A careful analysis of the experimental data indicates that for concentrations above φlcPPP the stacked lamellae start to coalesce to rather small liquid crystalline domains of nematically ordered stacks. These liquid crystalline domains can be individually very differently oriented but possess an overall preferred orientation over macroscopic length scales which becomes successively more expressed when further increasing φ PPP . The lower critical concentration for the formation of liquid crystalline domains of the DLPC-stabilized suspension compared to φlcPPP of the S100-stabilized suspension can be explained by a larger aspect ratio of the corresponding tripalmitin platelets. A geometrical model based on the excluded volumes of individual platelets and stacked lamellae has been developed and successfully applied to reproduce the critical volume fractions for both, the onset of stack formation and the appearance of the liquid crystalline phase

Organocatalytic Stereoselective Epoxidation of α-alkylidene Oxindoles Using α,α-diphenylprolinol in Liposome Membrane

We employed the membrane of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes suspended in water as a microenvironment for carrying out the organocatalytic epoxidation of an α-alkylidene oxindole. The reaction proceeds smoothly and displays diastereo- and enantio-selectivity that differs from what is achieved under bulk solution conditions. The potential of organocatalytic approaches for synthetic transformations in aqueous phase in the presence of dispersed membranes is briefly discussed

Organocatalytic Stereoselective Epoxidation of α-alkylidene Oxindoles Using α,α-diphenylprolinol in Liposome Membrane (Cover Feature)

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