Advanced therapeutic strategies and drug delivery approaches for management of oral submucosal fibrosis: a comprehensive review

Oral Submucous Fibrosis (OSF) is a chronic, progressive, and potentially malignant oral mucosal disorder that leads to development of trismus, burning sensations, mucosal blanching, and impaired oral function. Traditional treatments of OSF, including corticosteroids, hyaluronidase, antioxidants, and surgery, are limited due to poor drug delivery, systemic toxicity, and patient non-compliance. In this current scenario, the development of an advanced drug delivery system can be a potential strategy for OSF therapy, and emerging drug delivery strategies offer promising solutions by enabling localised, targeted, and sustained therapy. Novel drug delivery systems include Nanocarriers, Electrospun nanofibers, Mucoadhesive buccal patches, Microneedle systems, Biomaterial-based hydrogels, Stem cell-derived exosomes and many others, which help to provide the drug concentration at the target site for a longer time and give therapeutic effects that improve patient compliance by increasing the efficacy of the formulations for OSF treatment. Hydrogels, microneedle systems, and injectable therapies (e.g., hyaluronidase-dexamethasone, sodium hyaluronate with bioglass) provide regenerative, sustained, and minimally invasive treatment options with fewer adverse effects. Emerging approaches like stem cell-derived exosomes and gene therapy (miRNA-loaded nanoparticles) target fibrogenic pathways, reversing fibrosis and offering novel regenerative strategies. This review focuses on nanotechnology-based, mucoadhesive, injectable, and transmucosal delivery systems for managing OSF, highlighting targeted, persistent treatments by combining advanced drug-delivery systems. The study examines regenerative medicines, like exosomes and microRNA delivery methods, while providing insights into site-specific drug distribution and carrier optimization. Despite promising advancements, further clinical trials, safety data, and standardized guidelines are needed, and the OSF treatments should emphasize individualized, biomarker-guided approaches.