Characterization, antifungal potential, cytocompatibility, and regenerative potential of mucoadhesive gel containing antifungal‐β‐cyclodextrin inclusion complexes

PURPOSE: This study aimed to characterize a mucoadhesive gel containing nystatin (NYS) or chlorhexidine (CHX), complexed or not with β-cyclodextrin (βCD), and evaluate its rheological and mucoadhesive properties, antifungal efficacy, cytocompatibility, and collagen synthesis potential. MATERIALS AND METHODS: Mucoadhesive formulations were produced using chitosan and hydroxyethylcellulose, incorporating NYS or CHX at 32 mg/g, or complexed with βCD (NYS:βCD, equivalent to 16.1 mg/g of NYS, and CHX:βCD, equivalent to 4.8 mg/g of CHX), and compared to a pure gel (GEL) and a commercially available 2% miconazole gel (DK). The formulations were evaluated for their rheological and mucoadhesive properties; antifungal activity against Candida albicans by halo inhibition, XTT metabolic assay, minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC); cytocompatibility in an organotypic oral mucosa model by LIVE/DEAD and Alamar Blue metabolic assay; and collagen synthesis potential by fluorometric quantification. All microbiological and cytocompatibility tests were performed using mucoadhesive leachates. Statistical analysis was performed (α = 0.05). RESULTS: Elastic behavior was predominant in the formulations, and greater mucoadhesiveness was observed in the complexed groups (p < 0.05). Limited antifungal activity was found in the GEL and DK groups, while the NYS, NYS:βCD, CHX, and CHX:βCD formulations exhibited significantly superior antifungal efficacy (p < 0.05). While formulations containing CHX significantly reduced cellular metabolic activity, those containing NYS demonstrated better cytocompatibility and increased collagen production. CONCLUSION: The mucoadhesive gel containing NYS:βCD optimized both antifungal activity without compromising its rheological, mucoadhesive properties, and cytocompatibility at lower therapeutic doses compared to noncomplexed NYS. These findings suggest significant advantages for the treatment of oral candidiasis.