Characterization of Permeation Enhancers Effects: From High-Content Morphological Mapping to Molecular Dynamics

King Buwaila – MSc. student, Department of Pharmacy, Uppsala University; Shakhawath Hossain – Postdoctoral researcher, Department of Pharmacy, Uppsala University; Rosita Kneiszl – PhD researcher, Department of Pharmacy, Uppsala University; Per Larsson – Associate Professor, Department of Pharmacy, Uppsala University; Maria Karlgren – Associate Professor, Department of Pharmacy, Uppsala University

Introduction: The intestinal epithelial barrier restricts the oral delivery of macromolecules. Permeation enhancers (PEs) such as sodium caprate (C10) and SNAC can increase absorption, but their global impact on cellular organelles and their underlying mechanisms is poorly understood (1). Although SNAC is used clinically, standard assays lack the resolution to map subcellular phenotypic changes. This study integrates Cell Painting (2), permeability assays, and physics-based simulations (3) to provide a high-resolution characterization of the mechanistic and morphological alterations induced by PEs.