Bioinspired pullulan-based adhesive coacervate films for targeted buccal delivery of peptides

Mussel-inspired coacervation offers a powerful strategy for underwater adhesion; however, translating this chemistry into scalable drug delivery platforms remains challenging. Here, we present a bioinspired adhesive coacervate, integrating catechol/gallol-mediated adhesion with mucoadhesion principles to produce a manufacturable, patient-friendly film for buccal peptide delivery. Using tannic acid (TA) and pullulan-methacrylate (PUL-MA), adhesive coacervates were formulated and processed by slot-die coating into dual-layer films consisting of (i) an active mucoadhesive layer (ML) containing a GLP-1 receptor agonist (GLP-1-RA) and a permeation enhancer, sodium glycodeoxycholate (GDC), and (ii) a cellulose-based backing layer (BL). Slot-die processing enabled uniform film fabrication while preserving GLP-1-RA peptide structural integrity. By tuning PUL methacrylation degree (MD), material properties including film swelling, cohesion, and adhesion were optimized. PUL at a 3% MD level exhibited ~ five-fold higher adhesion (102.6 ± 14.2 J/m 2 ) than conventional buccal films. In ex vivo assays, the same formulation also achieved the highest peptide permeation (7.2 ± 9.1%), indicating that stronger mucoadhesion enhances tissue residence and facilitates transbuccal transport. Overall, this study demonstrates for the first time the successful integration of mussel-inspired coacervation with mucoadhesive film engineering, enabling a scalable and non-invasive platform for buccal administration of poorly permeable peptides, bridging bioinspired chemistry and drug delivery.