Smart control lipid-based nanocarriers for fine-tuning gut hormone secretion

Modulating the endogenous stores of gastrointestinal hormones is considered a promising strategy to mimic gut endocrine function, improving metabolic dysfunction. Here, we exploit mouse and human knock-in and knockout intestinal organoids and show that agents used as commercial lipid excipients can activate nutrient-sensitive receptors on enteroendocrine cells (EECs) and, when formulated as lipid nanocarriers, can bestow biological effects through the release of GLP-1, GIP, and PYY from K and L cells. Studies 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). This study demonstrates 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.