Nanoparticle-incorporated bilayer tamarind seed polysaccharide/pullulan films with sustained mucoadhesion for oral ulcer therapy.

The low drug loading capacity of oral films critically restricts their therapeutic potential, posing a primary limitation to their broader applicability. To improve the loading and delivery efficiency of oral films, bilayer films were developed, consisting of a mucoadhesive pullulan layer loaded with resveratrol-bovine serum albumin nanoparticles (Res-BSA) and a hydrophobic backing layer based on tamarind seed polysaccharide. The content of Res-BSA in the bilayer film was enhanced by increasing Res-BSA concentration (0-50%) in the mucoadhesive layer or by augmenting the mucoadhesive layer content at a fixed Res-BSA concentration (20%). The effects of increased Res-BSA content on the mechanical properties of the bilayer film could be mitigated by the backing layer, thereby preserving its flexibility. Resveratrol was continuously released from the bilayer films containing Res-BSA for over 12 h, demonstrating good antibacterial activity. The bilayer film containing 20% Res-BSA (TSP/Pul-1:1-20%) was effective in promoting cell migration and could provide a protective barrier for the oral mucosa through its sustained mucoadhesion (lasting over 12 h in vivo). In the rat oral ulcer model, TSP/Pul-1:1-20% accelerated ulcer healing by promoting re-epithelialization, increasing collagen deposition, and reducing inflammation. Additionally, TSP/Pul-1:1-20% may modulate the oral microbiota, partially shifting its composition toward a normal-like state. These results demonstrated that the bilayer films containing Res-BSA could be a promising platform for local oral treatment or transmucosal drug delivery.