Layer-by-layer polymeric films for buccal GLP-1 delivery

Buccal delivery can enable systemic peptide absorption while avoiding first-pass metabolism. Here, multilayer polymeric films fabricated by slot-die coating were developed for buccal delivery of a glucagon-like peptide-1 receptor agonist (GLP-1-RA) and the penetration enhancer sodium glycodeoxycholate (GDC). Dual- and triple-layer films formed distinct architectures with suitable thickness, mucoadhesion, epithelial compatibility, and preservation of GLP-1-RA secondary structure. Dual-layer films supported rapid co-release of GLP-1-RA and GDC, whereas triple-layer films enabled sustained, sequential release. In ex vivo porcine buccal tissue, triple-layer films enhanced permeation of both compounds compared to dual-layer films and reduced epithelial disruption relative to direct compound application. These results show that multilayer film design can modulate release kinetics, improve peptide transport across buccal tissue, and reduce tissue stress, supporting the potential of buccal films for systemic peptide delivery.