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Systèmes colloïdaux lipidiques pour l’administration par voie orale

Abstract : Ulcerative colitis (UC) is an Inflammatory Bowel Disease (IBD) and it is still nowadays incurable. Beyond the administration of anti-inflammatory drugs, including curcumin (CC), one of the pathways to be explored is the repair of the intestinal mucosa by an exogenous supply of phosphatidylcholine (PC) and lysophophatidylcholine, which are over 70% deficient in patients with RH. To address this issue, we were interested in the design of lipid systems for the oral delivery and allowing the simultaneous carry of CC and PC. We first explored the nature of the interactions involved between the two active ingredients within two model membrane systems, liposomal bilayers and monolayers (or Langmuir films). It turns out that the keto/enol equilibrium of curcumin and therefore the interaction with PC is influenced by both concentration and confinement. On the other hand, the addition of a ceride, cetyl palmitate, complexing curcumin allows, for some compositions, the miscibility with PC while stiffening the as obtained mixture. Based on these results, we formulated various dispersions of solid lipid particles, by varying the methodology of colloidal engineering, diffusion-solvent evaporation vs double emulsion and the nature of the stabilizer, emulsifiers vs nanoparticles. The suspension obtained by the double emulsion method appears as the most efficient in terms of encapsulation, protection in simulated gastric medium and sustained release of the active ingredients in a simulated intestinal medium. Finally, the ability of solid nanoparticles to stabilize the solid / liquid interface of SLNs, similar to the Pickering effect, has also been demonstrated. The entire study is a proof of concept regarding the potential of solid lipid nanoparticle suspensions for the oral administration of curcumin and exogenous phosphatidylcholine.
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Maxime Girardon. Systèmes colloïdaux lipidiques pour l’administration par voie orale. Chimie. Université de Lorraine, 2019. Français. ⟨NNT : 2019LORR0236⟩. ⟨tel-02553608⟩

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