Hani Shkolnikov-Lozober, Gleb Vasilyev, Salim Hadad, Rita Vilensky, Ron Avrahami, Arkadi Arinstein, Iyad Khamaysi, Eyal Zussman
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition primarily managed with topical corticosteroids such as budesonide. While commercial treatments exist, clinical outcomes are frequently hindered by inadequate drug retention on the esophageal mucosa. To enhance targeted delivery and mucosal retention, this study presents a mucoadhesive oral formulation consisting of a suspension of budesonide-embedded short cellulose acetate (CA-B) fibers. The fibers (mean diameter 0.2 μm and length 138 μm) were suspended in a 0.5% (w/v) aqueous alginate solution to optimize mucoadhesion. Rheological characterization revealed a critical fiber concentration threshold of 0.1% (w/v) for CA-B network formation, above which the suspension transitions into a highly structured, viscoplastic system with pronounced solid-like behavior. Upon administration, the short CA-B fibers mechanically interlock and conform to the mucosal surface, enabling sustained drug release and subsequent tissue diffusion. Formulation efficacy was validated through ex vivo mucoadhesion assays utilizing a porcine esophageal model. In vitro release kinetics followed a first-order model predicting a maximum cumulative budesonide release of 74%. Furthermore, transport modeling determined the optimal inter-fiber distance to achieve a sustained, localized therapeutic dose of budesonide at the mucosal surface. This suspendable short-fiber platform provides a robust strategy for enhancing mucosal retention in EoE, with broad applicability for targeted drug delivery across mucosal barriers.