Chitosan-Based Therapeutic Systems for Superficial Candidiasis Treatment. Synergetic Activity of Nystatin and Propolis

The paper deals with new approaches to chitosan (CS)-based antifungal therapeutic formulations designed to fulfill the requirements of specific applications. Gel-like formulations were prepared by mixing CS dissolved in aqueous lactic acid (LA) solution with nystatin (NYS) powder and/or propolis (PRO) aqueous solution dispersed in glycerin, followed by water evaporation to yield flexible mesoporous (pore widths of 2–4 nm) films of high specific surfaces between 1 × 103 and 1.7 × 103 m2/g. Morphological evaluation of the antifungal films showed uniform dispersion and downsizing of NYS crystallites (with initial sizes up to 50 μm). Their mechanical properties were found to be close to those of soft tissues (Young’s modulus values between 0.044–0.025 MPa). The films presented hydration capacities in physiological condition depending on their composition, i.e., higher for NYS-charged (628%), as compared with PRO loaded films (118–129%). All NYS charged films presented a quick release for the first 10 min followed by a progressive increase of the release efficiency at 48.6%, for the samples containing NYS alone and decreasing values with increasing amount of PRO to 45.9% and 42.8% after 5 h. By in vitro analysis, the hydrogels with acidic pH values around 3.8 were proven to be active against Candida albicans and Candida glabrata species. The time-killing assay performed during 24 h on Candida albicans in synthetic vagina-simulative medium showed that the hydrogel formulations containing both NYS and PRO presented the faster slowing down of the fungal growth, from colony-forming unit (CFU)/mL of 1.24 × 107 to CFU/mL < 10 (starting from the first 6 h)