Elena Eva Julianne Marxer

Philipps University of Marburg, Marburg, Hesse, Germany

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Publications (7)31.28 Total impact

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    ABSTRACT: Ultrasound is a common tool for clinical diagnosis due to its safety and economic. Especially the addition of ultrasound contrast agents leads to a high diagnostic reliability. In recent years ultrasound has been used as a trigger for directed drug delivery or to enhance thrombolysis. We developed a nanoscaled ultrasound contrast agent (NUSCA) to improve these applications. In the future drugs can be incorporated into this contrast agent to achieve a combination of ultrasound diagnosis and therapy. The aim of the present study is to elucidate the structure of the nanoscaled lipid formulations and a potential dependence of the ultrasound contrast enhancement on this structure. Our NUSCA is based on the phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and the single-chained polyethylene glycol (40) stearate (PEG40S). In this study the effect of increasing concentrations of the single chained PEG40S on the structure of the lipid formulations was characterised using Dynamic Light Scattering, cryo-Transmission Electron Microscopy, Nuclear Magnetic Resonance spectroscopy, lipid monolayer studies and epifluorescence measurements. In addition, the ultrasound contrast enhancement for the formulations was determined in vitro. Dependence between structure and ultrasound contrast was found. All PEG40S concentrations lead to a mixture of liposomes and discoid micelles. With increasing PEG40S content the amount of micelles increased. Certain PEG40S concentrations lead to an ultrasound contrast superior to the contrast of the commercially available ultrasound contrast agent SonoVue(®).
    Colloids and surfaces B: Biointerfaces 05/2014; 117:206–215. DOI:10.1016/j.colsurfb.2014.02.029 · 4.15 Impact Factor
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    ABSTRACT: Designed for gene therapy of chronic diseases, HBP-DEAPA 60 is a non-toxic biodegradable amine modified hyperbranched polyester. This candidate was chosen from a series of hyperbranched polymers for further characterization as it showed the best transfection efficiency and fastest degradation rate. HBP-DEAPA 60/DNA complexes were investigated with regard to stability, uptake and formation to gain a better insight into HBP-DEAPA 60/DNA complex properties. We investigated HBP-DEAPA 60/DNA complex uptake into A 549 cells by FACS and CLSM. Their stability was investigated by a heparin displacement assay as well as by DNAse I assay. Morphology was shown by AFM. HBP-DEAPA 60/DNA complex formation was further characterized in terms of thermodynamic parameters. We studied the conformation of DNA in nano-complexes via circular dichroism (CD) spectroscopy for different NP ratios. Thermodynamic studies showed that binding enthalpies were endothermic; the nano-complex formation was entropically driven. Although PEI/DNA and HBP-DEAPA 60/DNA complexes showed similar behavior with regard to uptake, heparin stability, DNA helicality and their entropically driven complex formation they differ in their binding constant K(a) and in their ability to protect the DNA from DNAse. Concerning K(a) and DNAse stability, HBP-DEAPA/DNA complexes should be further optimized. This shows that different characterization studies are necessary to fully characterize polyplex stability and properties.
    International Journal of Pharmaceutics 07/2012; 436(1-2):97-105. DOI:10.1016/j.ijpharm.2012.06.065 · 3.65 Impact Factor
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    ABSTRACT: Upon contact with the human body, nanomaterials are known to interact with the physiological surroundings, especially with proteins. In this context, we explored analytical methods to provide biologically relevant information, in particular for manufactured nanomaterials as produced by the chemical industry. For this purpose, we selected two batches of SiO(2) nanoparticles as well as four batches of CeO(2) nanoparticles, each of comparably high chemical purity and similar physicochemical properties. Adsorption of serum proteins and bovine serum albumin (BSA) was quantified by SDS-PAGE in combination with densitometry and further investigated by atomic force microscopy (AFM) and analytical ultracentrifugation (AUC). The protein adsorption to SiO(2) nanoparticles was below the limit of detection, regardless of adjusting pH or osmolality to physiological conditions. In contrast, the four CeO(2) nanomaterials could be classified in two groups according to half-maximal protein adsorption. Measuring the work of adhesion and indention by AFM for the BSA-binding CeO(2) nanomaterials revealed the same classification, pointing to alterations in shape of the adsorbed protein. The same trend was also reflected in the agglomeration behavior/dispersibility of the four CeO(2) nanomaterials as revealed by AUC. We conclude that even small differences in physicochemical particle properties may nevertheless lead to differences in protein adsorption, possibly implicating a different disposition and other biological responses in the human body. Advanced analytical methods such as AFM and AUC may provide valuable additional information in this context.
    ACS Nano 05/2012; 6(6):4603-14. DOI:10.1021/nn202657q · 12.88 Impact Factor

  • Ultrasound in Medicine & Biology 08/2011; 37(8). DOI:10.1016/j.ultrasmedbio.2011.05.479 · 2.21 Impact Factor
  • Jens Schäfer · Elena Eva Julianne Marxer · Udo Bakowsky ·
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    ABSTRACT: The contact of nanoparticle surfaces with biomolecules often results in interactions. Proteins as one of the most important biomolecules adsorb on nanoparticle surfaces and can affect the way of recognition or of uptake in the cell. Even inhaled nanoparticles can be found on the luminal side of airways and alveoli, major lung tissue compartment or cells and within capillaries. They cross the cell membrane not by endocytotic processes, but by diffusion or adhesive interactions. Due to the possible interaction after inhalative exposure of inorganic nanoparticles with blood biomolecules we investigated the adhesion properties between different TiO2 nanoparticles and commercial silicon or BSA (as a model protein) modified cantilevers with atomic force microscopy (AFM). The characterization of the nanoparticles was done using laser doppler electrophoresis (LDE), dynamic light scattering (DLS) and transmission electron microscopy (TEM) for zeta potential and size. AFM was used to perform force measurements with unmodified tips and BSA functionalized tips. Adhesion measurements showed differences between the inorganic nanoparticles, regarding their ability to interact with the major serum compound BSA. Scheme of the adhesion measurements on TiO2 nanoparticles performed with unmodified and BSA modified cantilevers.
    Physica Status Solidi (A) Applications and Materials 06/2011; 208(6):1320 - 1326. DOI:10.1002/pssa.201001110 · 1.62 Impact Factor
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    ABSTRACT: In the present study, we investigated the sonothrombolytic effect of new nanoscaled lipid formulations in human blood clots, using diagnostic ultrasound. Human blood clots of 1 ml were incubated with 1 μl of the different lipid dispersions DPPC/CH, DPPC/PEG40S, DSPC/PEG40S and the commercially available ultrasound contrast agent SonoVue®. Clots were stored for 3 days at 5 °C to obtain maximal clot retraction and lytic resistance. Each clot weight was determined before and after continuous insonation for 1h of insonation at 1.4 MHz. The pressure in the insonation chamber was 80 mm Hg to mimic middle arterial blood pressure. There were no significant differences in thrombus weight before insonation. All nanoscaled formulations and SonoVue® were able to reduce thrombus weight compared to the weight loss of clots that were not insonated but kept under pressure for one hour (p < 0.001). We found a highly significant weight reduction with DSPC/PEG40S compared to SonoVue® (p = 0.007). Nanoscaled DSPC/PEG40S dispersion could be a promising formulation in ultrasound enhanced thrombolysis even without thrombolytic drugs. Stable cavitation is a crucial parameter in fragmentation of thrombus architecture. Further studies of physicochemical properties of DSPC/PEG40S are necessary to corroborate our hypothesis.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 12/2010; 77(3):424-9. DOI:10.1016/j.ejpb.2010.12.003 · 3.38 Impact Factor
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    ABSTRACT: Ultrasound contrast agents are widely used in clinical diagnosis. In recent years, the use of ultrasound contrast agents as therapeutic agents has gained a lot of attention. Of special interest are ultrasound-enhanced gene delivery in various tissues (e.g. cardiac, vascular, skeletal muscle and tumor tissue), ultrasound-enhanced protein delivery (e.g. insulin delivery) and ultrasound-enhanced delivery of small chemicals (e.g. doxorubicin, vancomycin). Commercially available ultrasound contrast agents such as SonoVue® or Optison® are ranged in a size of 2-8 μm. These micronscaled agents show a good ultrasound contrast enhancement and thus they are used for diagnostic imaging. But they are not suitable for targeted drug delivery to tumor tissues or blood clots because for these applications particles smaller than 700 nm are needed. In the present study, we developed new nanoscaled ultrasound contrast agents with a size between 70 and 300 nm. The lipid formulations show excellent contrast intensities using diagnostic ultrasound of about 1.4 MHz. The negatively charged colloidal dispersions are long-time stable under physiological conditions without loss of ultrasound reflectivity. The adjustable supramolecular organization of the carriers depends on the composition and varies from micellar to liposomal structures. The small size and the circulation stability of these systems make them promising for novel diagnostics and controlled drug release applications.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 12/2010; 77(3):430-7. DOI:10.1016/j.ejpb.2010.12.007 · 3.38 Impact Factor