Jean-Christoph Leroux "Friendship between streptococci and extracellular matrix: a gold mine to find targets for new anti-infectives"

HIPS Talk

  • Überblick

    Traditionally, colloids such as liposomes, nanoparticles and polymers have been used in pharmaceutical sciences as delivery systems for drugs and imaging agents. There are, however, cases where they can treat diseases or intoxications by removing endogenous or exogenous toxic compounds from the body. Well known examples are activated charcoal and the polymeric binder sevelamer, which are indicated in the treatment of drug overdose and hyperphosphatemia, respectively. In the past few years, the field of biodetoxification has indeed experienced a rapid growth with the emergence of highly active sequestering colloids, and their evaluation in novel indications (e.g. infections, inflammation). In this presentation, we will cover three applications, namely the treatment of calcium channel blocker intoxications, celiac disease (i.e. autoimmune enteropathy triggered by gluten in genetically sensitive individuals) and Clostridum difficile infections where liposomes and polymeric binders can function as effective sequestrants. Transmembrane pH-gradient liposomes were optimized to extract from serum the calcium channel blockers diltiazem and verapamil. When the liposomes were intravenously injected to rats one hour after an oral dose of verapamil, the plasmatic drug levels increased dramatically indicating a redistribution of verapamil in the blood compartment. This resulted in an attenuation of the pharmacological activity of the drug and a faster recovery of cardiovascular parameters after an overdose. In the case of celiac disease, a polymeric binder was designed to sequester the immunogenic protein fraction of gluten in the gastrointestinal tract. In a transgenic mouse model of gluten sensitivity, the oral administration of the polymeric binder prior to gluten intake reduced the immunogenic response and the deleterious effects of gluten on the intestinal mucosa. Moreover, the polymer was not absorbed and excreted in the feces. This approach could represent a potential adjuvant therapy to a gluten free diet in unresponsive patients. Lastly, we will present some preliminary data on a novel polymeric binder which binds specifically to the toxins’ receptor-binding domain of C. difficile toxins. This approach is aimed inhibiting uptake of the toxins by gastrointestinal cells and reducing toxin-mediated toxicity. Financial support from the Swiss National Science Foundation is acknowledged.


    Datum: 13.11.2012, 17:00

    Veranstaltungsort

    Universität des Saarlandes

    Gebäude und Raum

    Bernd-Eistert-Hörsaal

    Referent

    Jean-Christoph Leroux,
    ETH Zürich

    Gastgeber

    Claus-Michael Lehr

  • Anfahrt

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