Petasol Exhibits Rapid and Efficient Epithelial Transport in Epithelial Barrier Models

The epithelial permeability of petasol, a sesquiterpene derivative with reported antiviral properties, remains largely unexplored despite its potential as a therapeutic candidate. Here, we systematically characterize the transport of petasol across epithelial barriers using a combination of in vitro transwell models, automated millifluidic sampling, mathematical modeling, optical- and HPLC-mass spectroscopy. Vero E6 and Caco-2 cell layers were employed as epithelial barrier models, with transepithelial electrical resistance (TEER) measurements confirming the formation of functionally intact epithelial layers. Mathematical modeling of passive diffusion and cellular uptake allowed estimation of key transport parameters, including permeability coefficients and intracellular sequestration rates. Trans-barrier transport of petasol was compared to that of nitazoxanide, chloroquine, and FITC-dextran. Our results reveal that petasol exhibits efficient and rapid transport across both epithelial cell types without substantial intracellular accumulation or metabolic degradation, suggesting favorable properties for systemic delivery.