Digestion-triggered double emulsions enhance oral octreotide and FD-4 permeability via in situ fatty acid generation

Oral delivery of peptide therapeutics faces significant hurdles, primarily due to rapid gastrointestinal degradation and poor epithelial permeability across the intestinal barrier. Current injectable peptide therapies, while effective, often lead to patient non-compliance. While some oral formulations exist, like oral semaglutide using sodium caprate (C10) as an absorption enhancer, these often rely on high local concentrations of enhancers that can transiently alter membrane fluidity or tight junction integrity. A major gap remains in developing strategies that enable controlled, localized generation of permeation enhancers specifically at the site of absorption, minimizing systemic exposure and potential side effects while maximizing peptide bioavailability. This study addresses this by designing a novel emulsion system.