Journal: Drug Delivery and Translational Research

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Publisher

Springer

Journal Volumes

ISSN

2190-393X
2190-3948

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2016 - 201912020 - 20254
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Publications 1 - 5 of 5
  • The intracellular visualization of exogenous DNA in fluorescence microscopy
    Item type: Journal Article
    Greitens, Christina; Leroux, Jean-Christophe; Burger, Michael (2024)
    Drug Delivery and Translational Research
    In the development of non-viral gene delivery vectors, it is essential to reliably localize and quantify transfected DNA inside the cell. To track DNA, fluorescence microscopy methods are commonly applied. These mostly rely on fluorescently labeled DNA, DNA binding proteins fused to a fluorescent protein, or fluorescence in situ hybridization (FISH). In addition, co-stainings are often used to determine the colocalization of the DNA in specific cellular compartments, such as the endolysosomes or the nucleus. We provide an overview of these DNA tracking methods, advice on how they should be combined, and indicate which co-stainings or additional methods are required to draw precise conclusions from a DNA tracking experiment. Some emphasis is given to the localization of exogenous DNA inside the nucleus, which is the last step of DNA delivery. We argue that suitable tools which allow for the nuclear detection of faint signals are still missing, hampering the rational development of more efficient non-viral transfection systems.Graphical abstract The intracellular visualization of exogenous DNA in fluorescence microscopy. Created with BioRender.com.
  • Intravenous injection of cyclosporin A loaded lipid nanocapsules fights inflammation and immune system activation in a mouse model of diabetic retinopathy
    Item type: Journal Article
    Bohley, Marilena; Dillinger, Andrea E.; Braunger, Barbara M.; et al. (2023)
    Drug Delivery and Translational Research
    Inflammation and immune system activation are key pathologic events in the onset and escalation of diabetic retinopathy (DR). Both are driven by cytokines and complement originating from the retinal pigment epithelium (RPE). Despite the RPE's pivotal role, there is no therapeutic tool to specifically interfere with the RPE-related pathomechanism. A therapy that addresses RPE cells and counteracts inflammation and immune response would be of paramount value for the early treatment of DR, where currently are no specific therapies available. Here, we utilized lipoprotein-mimetic lipid nanocapsules to deliver the anti-inflammatory and immunosuppressive drug cyclosporin A (CsA) to RPE cells. Using a mouse model of DR that mirrors all pathologic aspects of human DR, we demonstrate that intravenously applied CsA-loaded lipid nanocapsules comprehensively counteract inflammation and immune system activation. One single injection suppressed the expression of pro-inflammatory cytokines, dampened macrophage infiltration, and prevented macrophage and microglia activation in eyes with DR. This work shows that CsA-loaded lipid nanocapsules can offer new avenues for the treatment of DR.
  • Development of a diffusion-weighed mathematical model for intradermal drainage quantification
    Item type: Journal Article
    Kirsch, Christoph; Fehr, Daniel; Babity, Samuel; et al. (2022)
    Drug Delivery and Translational Research
    The quantitative assessment of lymphatic dermal clearance using NIR fluorescent tracers is particularly important for the early diagnosis of several potential disabling diseases. Currently, half-life values are computed using a mono-exponential mathematical model, neglecting diffusion of the tracer within the dermis after injection. The size and position of the region of interest are subjectively manually selected around the point of injection on the skin surface where the fluorescence signal intensity is averaged, neglecting any spatial information contained in the image. In this study we present and test a novel mathematical model allowing the objective quantification of dermal clearance, taking into consideration potential dermal diffusion. With only two parameters, this "clearance-diffusion" model is simple enough to be applied in a variety of settings and requires almost no prior information about the system. We demonstrate that if dermal diffusion is low, the mono-exponential approach is suitable but still lacking objectivity. However, if dermal diffusion is substantial, the clearance-diffusion model is superior and allows the accurate calculation of half-life values.
  • Lipid-based drug delivery systems in the treatment of wet age-related macular degeneration
    Item type: Journal Article
    Du, Joanne D.; Fong, Wye-Khay; Caliph, Suzanne; et al. (2016)
    Drug Delivery and Translational Research
  • Isolation of bacterial extracellular vesicles from raw samples using a portable microstructured electrochemical device
    Item type: Journal Article
    Mantella, Valeria; Bienz, Siiri; Brigger, Finn; et al. (2025)
    Drug Delivery and Translational Research
    Bacterial extracellular vesicles (EVs) are nanosized vesicles released by both Gram-negative and Gram-positive bacteria, playing critical roles in microbial communication, host-pathogen interactions, and immune modulation. Despite their significance in research and clinical applications, conventional isolation methods, such as ultracentrifugation (UC), are often slow, labor-intensive, and susceptible to contamination. In this study, we evaluated a novel portable microstructured electrochemical device (PMED) designed for rapid and selective bacterial EV isolation directly from biological samples. Using immunoaffinity-based capture and voltage-triggered release, the device-isolated EVs from Gram-negative Escherichia coli (E. coli), Gram-positive Lactobacillus fermentum (Lb. fermentum) culture supernatants and from urine samples spiked with E. coli , showing superior purity compared to UC. Characterization through nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), and Western blot confirms enhanced selectivity and reduced contaminants. Functional assays demonstrated that device-isolated Lb. fermentum EVs selectively activated Toll-like receptor 4 (TLR4) without triggering TLR2, unlike UC-isolated EVs, suggesting a more refined immunomodulatory effect. These findings highlight the device’s translational potential for EV-based diagnostics, particularly for noninvasive urinary tract infection detection, and its broader applications in studying bacterial communication and immune regulation.
Publications 1 - 5 of 5