Protein Delivery Using Three-Dimensional Printing of Buccal Films: Technological Advances and Clinical Potential

Therapeutic proteins have emerged as a cornerstone of modern medicine due to their high specificity and strong biological effects. However, delivering these proteins poses significant challenges due to their instability, susceptibility to enzymatic breakdown, low permeability, and reliance on invasive parenteral routes. Buccal drug delivery is a promising non-invasive alternative, offering quick systemic absorption while avoiding gastrointestinal degradation and hepatic first-pass metabolism. Three-dimensional (3D) printing as a fabrication method has further enhanced the potential of buccal delivery, enabling precise dosage control, multilayer structures, and patient-specific customization. This review focuses on the current state of the traditional and 3D-printed buccal film platforms using different printing methods for protein delivery, and critically analyzes protein stability challenges, and formulation strategies. The discussion further highlights emerging proof-of-concept studies.