Chitosan-celluloses wafers containing emulsified curcumin: a nano-in-matrix approach for buccal delivery

Oral surgical and periodontal procedures generate localized tissue damage that favors microbial colonization and delayed healing. Local mucoadhesive drug delivery systems capable of prolonged release may overcome the limitations of systemic therapies. Curcumin (CUR) exhibits antimicrobial and anti-inflammatory activities but is hindered by poor aqueous solubility and physiological instability. This study aimed to develop and characterize polymeric buccal wafers containing a CUR-loaded nanoemulsion as a nano-in-matrix system for sustained local delivery and antimicrobial protection in the oral cavity. Chitosan (CH)-based hydrogels, alone or combined with cellulose derivatives (HPMC or HPC), were loaded with a CUR-nanoemulsion and lyophilized to obtain porous wafers. Nanoemulsification improved CUR aqueous dispersibility and modulated hydrogel rheology, shifting the viscoelastic profile toward a more structured behavior. Among the formulations, CH:HPMC_low wafers had optimal performance, combining mucoadhesive strength (F_max 0.46 N), adequate puncture resistance, and sustained CUR release for up to 48 h. X-ray diffraction indicated reduced CUR crystallinity within the matrix, while FTIR confirmed physical entrapment without chemical interactions. CUR-loaded gels and wafers inhibited the growth of P. gingivalis and S. aureus (MIC of 6.25 and 100 µg/mL, respectively). Wafer extracts showed cytocompatibility with TR146 cells in all tested concentrations (up to 40 μg/mL). Despite increased water uptake, the wafers remained intact after 4 months of refrigerated storage, retaining 98.31% of CUR content. These findings support the potential of the developed wafers for further pre-clinical studies as buccal delivery systems for post-surgical oral care and prevention of microbial proliferation.