Bioactive Mucoadhesive Systems for Oral Ulcer and Stomatitis Management: From Traditional Topical Formulations to Advanced Biomaterials

Oral ulcerative and inflammatory mucosal diseases, exemplified by recurrent aphthous stomatitis (RAS) and cancer-therapy-induced oral mucositis (OM), remain challenging to treat locally because salivary clearance, enzymatic activity, mechanical movement and limited residence time constrain conventional topical drug delivery. This review examines mucoadhesive biomaterial platforms as functional delivery systems and asks whether their material properties—including retention, interfacial adhesion and controlled release—contribute therapeutic value beyond that attributable to the incorporated bioactive payload. Evidence for mucoadhesive tablets, buccal films and patches, hydrogels, polymeric nanocarriers, dissolving microneedles and electrospun systems is appraised according to an evidence hierarchy that distinguishes randomised clinical evidence from animal and in vitro findings. Mucoadhesive tablets have been associated with reductions in RAS ulcer diameter at days 5 and 7 in a small pooled analysis, while licorice-loaded dissolving and bioadhesive patches provide repeated clinical evidence for phytochemical delivery through mucoadhesive devices. Hydrogel and nanocarrier systems show preclinical benefits in wound healing and local delivery, including substantial dose sparing of triamcinolone acetonide in a microneedle platform, but remain without controlled clinical translation in the indications reviewed. Where evidence permits, retention and release are considered as material properties distinct from the biological responses they enable; however, existing studies rarely isolate the therapeutic contribution of the carrier from that of the payload. Priorities for translation include standardised mucoadhesion characterisation, physiologically relevant human oral mucosa models, botanical and phytochemical standardisation, and controlled trials comparing identical active agents in conventional versus mucoadhesive vehicles.