Fabrication of an Antifungal PMMA Denture Nanocomposite Functionalized with Miconazole-Pectin-Silver Nanoparticles against Denture Stomatitis.

Denture stomatitis is a highly prevalent oral mucosal infection caused by Candida biofilm formation on the denture surface. In this study, an antifungal polymethyl methacrylate (PMMA) denture nanocomposite (MCZ-P-AgNPs/PMMA) was prepared by incorporating miconazole-loaded pectin-stabilized silver nanoparticles (MCZ-P-AgNPs) into the PMMA matrix. Response surface methodology was used to finalize the synthesis of AgNPs via the pectin-mediated green reduction method. To address the poor aqueous solubility of miconazole, the β-cyclodextrin inclusion complexation strategy was employed. MCZ-P-AgNPs exhibited potent antifungal activity with an MIC80 of 40 μg/mL and an MFC of 80 μg/mL for Candida albicans (CA) and Candida glabrata (CG). Biofilm inhibition and eradication assays demonstrated a BIC80 of 40 μg/mL for CA and 20-40 μg/mL for CG, along with a BEC80 of 80 μg/mL for both species. Mechanistic investigations revealed ergosterol depletion, oxidative and nitrosative stress induction, and disruption of extracellular matrix components. Subsequently, MCZ-P-AgNPs were incorporated into PMMA (0.53 wt%) using conventional heat polymerization, developing MCZ-P-AgNPs/PMMA. Physicochemical characterization by ATR-FTIR, Vickers microhardness, and SEM-EDX analyses confirmed polymerization and successful nanoparticle integration. The nanocomposites exhibited low water sorption (8.6% after 60 days) and a high water contact angle (104.45 ± 0.49°), which indicated a hydrophobic surface maintaining material integrity. In vitro release profile demonstrated sustained miconazole release. ICP-MS analysis confirmed minimal silver-ion release from the nanocomposites. Antifungal evaluation showed reduced fungal adhesion and metabolic activity on the nanocomposite surface, confirmed by XTT assay, CFU enumeration, and crystal violet staining. Additionally, in vitro cytotoxicity assay on the HEK293 cell line and the seed germination study on Brassica rapa established biosafety and ecological compatibility of MCZ-P-AgNPs. Collectively, MCZ-P-AgNPs/PMMA nanocomposite offers a promising approach in transforming conventional PMMA into an inherently antifungal denture material against denture stomatitis.