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    Soutenance de thèse de Mr Thomas BRIOT

    Soutenance de thèse de Mr Thomas BRIOT

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    11 October 2018

    Titre : New decitabine nanoparticle formulations for acute myeloid leukemia treatments

    Directeur de Thèse: Pr Frédéric Lagarce

    Co-directrice de thèse : Dr Emilie Roger

    Abstract: The aim of this phD work was to develop nanoparticle formulations to improve patients’ quality of life in case of acute myeloid leukemia (AML). These formulations could, for example, allow an oral administration of decitabine. Three different formulations were developed: two were based on lipid nanocapsules (LNCs) with an encapsulation of decitabine or a decitabine prodrug (decitabine(C12)2). The third strategy was a liposomal formulation with a decitabine encapsulation. After being characterized on physico-chemical parameters, in vitro intestinal permeability studies were performed on LNCs strategies. One strategy was able to enhance decitabine permeability. Cell proliferation studies performed on human AML cell lines showed that encapsulations into LNCs improve decitabine and decitabine(C12)2 activities. In order to evaluate the potential of these formulations to enhance decitabine plasma half-life, their stabilities in human plasma were then  assayed. Free decitabine(C12)2 or encapsulated into LNCs has been shown to limit the rapid decitabine degradation. Finally, pharmacokinetic studies were performed. Decitabine encapsulation into LNCs with a previous decitabine prodrug synthesis was able to increase maximal plasma concentrations.

     

     

    Key words: Nanoparticle, Acute myeloid lekemia, decitabine, Pharmacokinetic.