A Dual-Action nanoemulsified mucoadhesive polymeric buccal film of curcumin–lidocaine: non-Invasive targeting oral mucositis treatment via MMP-9 and NF-κβ pathways

Oral mucositis (OM) is a debilitating condition that typically results from chemotherapy or radiotherapy, causing painful ulceration and inflammation in the oral cavity. This work optimised and tested a dual-action mucoadhesive buccal film containing curcumin (CUR) with lidocaine (LID) for the localised targeting treatment of OM to develope an anti-inflammatory and analgesic effects and mucosal healing. Mucoadhesive buccal films were formulated using a solvent casting technique based on nanoemulsion. Buccal films were produced combining plasticisers (PEG 400), hydrophilic polymers (PVA, HPMC, PVP), and permeation enhancers (Tween 80, Transcutol). The optimised formula have high folding endurance (>300 folds), uniform thickness (1.0 ± 0.01 mm), pH compatibility (6.7), and excellent drug content homogeneity (∼97% for LID and ∼96% for CUR). <i>In vitro</i>, the film released 95% of LID and 90% of CUR within 13 min. <i>Ex vivo</i> studies showed higher permeation of LID (95 µg/cm²) compared to CUR (80 µg/cm²). <i>In vivo</i>, the CUR-LID film significantly enhanced ulcer healing (∼95-100% by day 5), with complete mucosal regeneration and normalisation of inflammatory biomarkers to baseline levels. This work supports the CUR-LID buccal film as a prospective non-invasive platform for managing oral mucositis with better therapeutic outcomes, effective drug delivery, and prolonged mucosal contact.