Riboflavin- and Hypericin-Mediated Antimicrobial Photodynamic Therapy as Alternative Treatments for Oral Candidiasis: A Systematic Review.

Oral candidiasis, predominantly caused by , presents significant challenges in treatment due to increasing antifungal resistance and biofilm formation. Antimicrobial photodynamic therapy (aPDT) using natural photosensitizers like riboflavin and hypericin offers a potential alternative to conventional antifungal therapies. : A systematic review was conducted to evaluate the efficacy of riboflavin- and hypericin-mediated aPDT in reducing Candida infections. The PRISMA framework guided the selection and analysis of 16 eligible studies published between 2014 and 2024. Data on light parameters, photosensitizer concentrations, and outcomes were extracted to assess antifungal effects. : Both riboflavin- and hypericin-mediated aPDT demonstrated significant antifungal activity, achieving substantial reductions in Candida biofilm and planktonic cell viability. Riboflavin activated by blue light and hypericin activated by yellow or orange light effectively targeted fluconazole-resistant Candida strains with minimal cytotoxicity to host tissues. However, complete biofilm eradication remained challenging, and variations in protocols highlighted the need for standardization. : Riboflavin- and hypericin-mediated aPDT present promising, biocompatible alternatives for managing antifungal resistance in Candida infections. Further clinical trials and standardized protocols are essential to optimize outcomes and confirm efficacy in broader clinical settings.