Boosting buccal drug absorption: Mechanistic insights into bilosome-mediated delivery

Effective buccal drug delivery is limited by the barrier properties of the mucosa, necessitating innovative systems to enhance permeability without compromising tissue integrity. In this study, bilosomes composed of sodium glycodeoxycholate and phosphatidylcholine were evaluated as a nanoparticulate platform for buccal drug delivery. Their in vitro uptake was investigated using the TR146 buccal cell line. The bilosomes demonstrated stable physicochemical properties and no aggregation. Functional assays indicated that they transiently opened cell-cell junctions, promoting transport across the mucosal barrier while minimizing toxicity. Quartz crystal microbalance with dissipation monitoring confirmed specific interactions with barrier components, supported by observed modulation of desmosomal junctions and cellular uptake. <i>Ex vivo</i> studies using porcine buccal mucosa further showed concentration-dependent distribution. Collectively, these results suggest that bilosomes are a safe and effective platform for enhancing buccal drug absorption.