Design buccal film for systemic delivery of insulin.

OBJECTIVE: To review advanced mucoadhesive buccal films as a non-invasive platform for systemic insulin delivery.Significance:Buccal delivery may improve patient adherence and glycemic control by bypassing gastrointestinal degradation and first-pass hepatic metabolism. However, insulin transport across the buccal mucosa is limited by salivary washout, mucus barriers, enzymatic degradation, tight epithelial junctions, and insulin's large, hydrophilic nature. METHODS: This review examines formulation strategies designed to overcome these barriers, including insulin-loaded nanocarriers, permeation enhancers, and protease inhibitors incorporated into mucoadhesive film matrices, often with impermeable backing layers to direct drug release toward the buccal mucosa. Key design elements include polymer selection (e.g., chitosan derivatives, hydroxypropyl methylcellulose, alginate, and silk fibroin), nanocarrier systems (liposomes, micelles, and nanoparticles), and fabrication methods such as solvent casting, electrospinning, and 3D printing. RESULTS: Current approaches can improve residence time, protect insulin from degradation, enhance mucosal permeability, and support controlled release. Multicomponent films integrating mucoadhesive polymers with functional excipients and nanocarriers show the greatest promise for improving systemic insulin absorption. CONCLUSIONS: Mucoadhesive buccal films are a promising alternative for insulin administration. Future progress will likely depend on smart, stimuli-responsive formulations, especially glucose-responsive systems, and precision manufacturing approaches such as 3D printing. Clinical translation will require improved stability, permeability, standardization, and scalable production.