Gut hormone stimulation as a therapeutic approach in oral peptide delivery

Enteroendocrine cells (EECs) produce ~20 gut hormones that regulate a wide range of metabolic processes, in which most hormones have more than one physiological role and most of these physiological roles are performed by more than one hormone. Nutrients, such as lipids, can interact with various G-protein coupled receptors (GPCRs) expressed on EECs and induce the release of gut hormones. Lipids are widely present in a wide range of excipients used in nanocarriers. During the last years, my group has been working on the stimulation of gut hormones secretion via lipid nanocarriers orally administered in the context of type 2 diabetes, inflammatory bowel disease and metabolic-dysfunction associated steatotic liver disease treatment1-5. The goal of this strategy is to stimulate the secretion of gut hormones while simultaneously providing with plasmatic levels of the encapsulating peptide towards an oral delivery alternative to the subcutaneous peptide injection. Mechanistic tudies in wild-type, dysglycemic, and gut Gcg knockout mice demonstrated that the effect exerted by lipid nanocarriers could be modulated by varying the excipients (e.g., nature and quantities), the formulation methodology, and their physiochemical properties (e.g., size and composition)6. This presentation highlights the therapeutic potential of using nanotechnology to modulate release of multiple endogenous hormones from the enteroendocrine system through a patient-friendly, inexpensive, and noninvasive manner.