Ana Beloqui García - UCLouvain Exploiting the pathophysiology of the gut towards innovative treatments for gastrointestinal/metabolic diseases. The main limitation of current treatments relying on oral GLP-1 administration is their low and highly variable biovailability (1%). Studies in the field of metabolism exploring the physiological stimulation of GLP-1 secretion using different lipid ligands (e.g., butyrate, propionate) have failed to reach sufficiently high levels of GLP-1 in order for these to be considered as plausible treatments for metabolic disorders. We have developed a lipid-based drug delivery system (nanocapsules) that combines the physiological stimulation of endogenous gut hormone secretion (including GLP-1) with increased plasmatic levels of an encapsulated synthetic peptide. In addition, we have proven that this system does not only stimulate GLP-1, but also other gut hormones such as GLP-2, GIP or PYY. We were able to demonstrate the ability of these lipid-based nanocapsules to yield levels of the selected peptides that are therapeutically relevant in the context of different diseases, demonstrating the potential of this strategy to be used in the treatment of gastrointestinal/metabolic disorders (e.g., the so-called metabolic syndrome). This research has been conducted at the Advanced Drug Delivery and Biomaterials (Louvain Drug Research Institute) at the UCLouvain. The research has also benefited from the expertise of the research group of Prof. Patrice D. Cani (UCLouvain), the research groups of Prof. Fiona Gribble and Frank Reimann (University of Cambridge, UK) via the ERC starting grant project Nanogut and Prof. Daniel J. Drucker (University of Toronto, Canada). The nanocapsules described in this proposal are the subject of a patent (patent Lipid nanocapsules charged with incretin mimetics (PCT/EP2020/064766 24.12.2020)).