Gellan gum formulations containing natural polyphenolic compounds to treat oral candidiasis

Oral candidiasis (OC) is caused by Candida albicans, targeting immunocompromised individuals and developing drug resistance, highlighting the need for advanced therapeutics. Polyphenols such as caffeic acid phenethyl ester (CAPE) and ellagic acid (EA) display antifungal and immune-modulating properties. Incorporating CAPE and EA in gellan gum (GG) formulation enhances their applicability and effectiveness against OC. We developed GG-based formulations loaded with CAPE (1,000 µg/mL), EA (1,000 µg/mL), or CAPE + EA (1,000 µg/mL each) against C. albicans. GG formulations containing gellan (0.6% and 1.0%), genipin (5 mM), polyethylene glycol 400 (0.5%), and sorbitan monooleate 80 (0.5%) demonstrated enhanced release of CAPE and EA. The 0.6% GG formulation reduced C. albicans CFU by 2–6 log₁₀ within 30 min (P < 0.05) and biofilm mass by 48% (CAPE, P = 0.0034), 60.7% (EA, P = 0.0980), and 70% (CAPE + EA, P = 0.0181). Both 0.6% and 1.0% GG formulations inhibited hyphae (P < 0.0001). GG formulations showed high viability of human red blood cells (92%–94%) and human gingival cells (61%–69%). In artificial chewing simulations (ACS), 0.6% GG exhibited 67.7% (30 min), 55.9% (60 min), and 35.8% (120 min) for CAPE release, and 48.2% (30 min), 45.1% (60 min), and 42.1% (120 min) for EA. In 1% GG, about 44.07% (30 min), 43.8% (60 min), and 29.5% (120 min) of CAPE and 55.8% (30 min), 49.6% (60 min), and 50.6% (120 min) of EA were released. The present study is the first to evaluate the efficacy of CAPE- and EA-loaded GG formulations against C. albicans under ACS, thereby supporting their potential development for OC treatment.