Zerumbone With Photodynamic Therapy Combats Candida Biofilms and is Biocompatible

Objectives: This study evaluated the antibiofilm activity and biocompatibility of Zerumbone (ZER) combined with Antimicrobial Photodynamic Therapy (aPDT) against a non-infected (3D-NI) and infected (3D-I) three-dimensional (3D) coculture model involving two oral cell lines.
Methods: The 3D-I groups were infected with fluconazole-susceptible (CaS) and resistant (CaR) Candida albicans and treated with ZER (256 and 512 µg/mL) combinated with aPDT [mediated by Photodithazine^® (200 mg/L) and LED (44.5 mW/cm²)]. As a control, 3D tissues were treated with nystatin (positive) or PBS (negative). The biocompatibility was evaluated using Alamar Blue^® for 3D-NI and LDH release for 3D-I. The antibiofilm efficacy was evaluated by colony-forming units (CFU/mL). Data were submitted to one-way ANOVA followed by Tukey or Games-Howell post-hoc test (α=5%).
Results: The 3D-NI treated with aPDT or combined with ZER (256 µg/mL) exhibited a significant (p≤0.002) reduction (≤19%) in cell viability. For 3D-I infected with CaS or CaR, all groups containing ZER alone or in association with aPDT, showed a smaller reduction (≤23%) in cell viability. CFU/mL analysis showed that ZER combined with aPDT resulted in the greatest reduction in CFU/mL. ZER at 256 and 512 µg/mL showed reductions of 2.36 and 2.64 log₁₀, respectively for CaS, while 2.15 and 2.81 log₁₀, respectively for CaR.
Conclusions: ZER combined with aPDT was effective against CaS and CaR biofilms and non-cytotoxic in a three-dimensional co-culture model. Further investigations using in vivo models and randomized clinical trials utilizing ZER combined with aPDT are recommended.