Oromucosal films for peptide delivery: formulation strategies using permeation enhancers and polymers

Buccal and sublingual mucosae offer highly vascularized, patient-acceptable routes for systemic peptide delivery, providing a promising alternative to peptide injections and conventional oral peptide dosage forms that suffer from enzymatic degradation, limited permeability, and hepatic first-pass metabolism. Despite these advantages, achieving consistent peptide bioavailability from oromucosal dosage forms remain challenging due to salivary washout, enzymatic instability, and the compact, lipid-rich epithelial structure. This review provides a comprehensive overview of formulation strategies developed to overcome these barriers, with an emphasis on the use of permeation enhancers (PEs), mucoadhesive polymers, and multilayer film architectures. Advances in nanoparticle-integrated films are highlighted for their potential to improve peptide stability and mucosal permeation. The review concludes by addressing patient compliance, translational potential, and regulatory perspectives that shape the clinical advancement of peptide-loaded oromucosal films.