Hydrogel-based drug delivery systems for oral mucositis: a systematic review of preclinical models and translational perspectives

INTRODUCTION: Oral mucositis (OM) remains a common and clinically significant complication of chemotherapy and radiotherapy. Current management is largely supportive, and effective local therapies remain limited. Hydrogel-based delivery systems have attracted interest because they may improve mucosal retention, protect ulcerated tissue, and enable sustained local drug release. METHODS: A systematic review of preclinical animal studies evaluating hydrogel-based interventions for oral mucositis was conducted. PubMed, Embase, and the Cochrane Library were searched, with additional gray literature screening. Data on formulation characteristics, experimental models, therapeutic outcomes, and methodological quality were extracted. Risk of bias was assessed using the SYRCLE tool. RESULTS: Eighteen studies met the inclusion criteria. Most formulations reduced lesion severity, improved histological healing, and attenuated inflammatory or oxidative markers. Multifunctional systems combining mucoadhesion with anti-inflammatory, antioxidant, or antimicrobial activity tended to show broader effects than conventional gels. However, study design, outcome reporting, and translational endpoints were heterogeneous. CONCLUSIONS: Current preclinical evidence supports hydrogels as promising local drug delivery platforms for oral mucositis. Greater standardization of models and clinically relevant endpoints will be important to support translation into human studies. PROTOCOL REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD420251072050.