Local drug delivery for oral squamous cell carcinoma under oral cavity.

Oral squamous cell carcinoma (OSCC) is a leading malignancy within head and neck cancers and is associated with substantial morbidity and mortality. Local drug delivery systems (LDDS) have emerged as an important strategy to increase site-specific drug exposure at oral lesions while limiting systemic distribution and associated toxicity. However, therapeutic success in the oral cavity is constrained by stringent "hard constraints," including continuous salivary flow, enzymatic degradation, pH variability, and mechanical abrasion from chewing and tongue movement, which collectively reduce residence time and destabilize labile payloads. This review synthesizes major LDDS platforms for OSCC, including mucoadhesive films/patches, oral sprays, in situ gelling systems, and injectable hydrogels, and critically analyzes how platform performance is governed by interactions between payload properties (small molecules, biologics, nucleic acids), lesion characteristics (accessibility, geometry, margin control), and patient-centered factors. We highlight the need for decision-oriented frameworks that link clinical scenarios to platform selection and recommend standardized evaluation metrics for retention under salivary flow, resistance to mechanical stress, and biochemical stability in saliva-relevant conditions. Despite rapid progress in materials and delivery technologies, OSCC-specific optimization and translational testing remain limited. Future work should prioritize biocompatible, durable systems capable of maintaining predictable local exposure and controlled release under clinically relevant oral conditions, supported by rigorous preclinical validation and well-designed clinical studies to improve outcomes in OSCC.