Formulation, in-vitro characterization and clinical evaluation of curcumin in-situ gel for treatment of oral submucosal fibrosis (OSF)

Background: Oral submucosal fibrosis (OSF) is a chronic oral mucosal disease with a cancerization tendency, characterized by restricted mouth opening and dysphagia. Currently, the mainstay treatment is still the local corticosteroid injection. Curcumin can reconstruct the redox balance, inhibit epithelial-mesenchymal transition (EMT), and suppress the excessive deposition of extracellular matrix (ECM) collagen, making it a promising treatment for fibrotic diseases. However, curcumin has poor intestinal absorption and low bioavailability, which limits its efficacy in treating oral mucosa diseases. Materials and Methods: In this study, we investigated a new administration mode and dosage form for curcumin in the treatment of OSF, and evaluated its clinical efficacy as an adjuvant therapy for OSF (Registration number: ChiCTR2400092888). The gel formulations were characterized by phase-transition temperature, phase-transition time, pH, viscosity, corrosion rate, in-vitro release rate, and chemical stability. The selected formulation was clinically evaluated in terms of inter incisor distance, mucosal pain index, mucosal color score, and mucosal texture score. Results: The final gel formula contained 18% poloxamer 407 (PLX407), 2% poloxamer 188 (PLX188), and 0.5% hydroxypropyl methylcellulose (HPMC). Curcumin was released as the gel underwent degradation. Gel characterization confirmed that its physicochemical properties met clinical requirements. The clinical study showed significant improvements in clinical indicators in both groups after one course of treatment. Notably, the gel, when used in conjunction with triamcinolone acetonide injections, significantly alleviated oral mucosal pain in OSF patients. Conclusion: This study demonstrates that curcumin thermosensitive in-situ gels, as a novel dosing regimen, can achieve painless management of OSF, which is also the novelty of this work.