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/m²) than conventional buccal films. In ex vivo assays, the same formulation also achieved the highest peptide permeation, 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.