ABSTRACT
Antimicrobial photodynamic therapy (aPDT) is an evolving treatment strategy against human pathogenic microbes such as the Candida species, including the emerging pathogen C. auris. Using a modified EUCAST protocol, the light-enhanced antifungal activity of the natural compound parietin was explored. The photoactivity was evaluated against three separate strains of five yeasts, and its molecular mode of action was analysed via several techniques, i.e., cellular uptake, reactive electrophilic species (RES), and singlet oxygen yield. Under experimental conditions (λ = 428 nm, H = 30 J/cm2, PI = 30 min), microbial growth was inhibited by more than 90% at parietin concentrations as low as c = 0.156 mg/L (0.55 µM) for C. tropicalis and Cryptococcus neoformans, c = 0.313 mg/L (1.10 µM) for C. auris, c = 0.625 mg/L (2.20 µM) for C. glabrata, and c = 1.250 mg/L (4.40 µM) for C. albicans. Mode-of-action analysis demonstrated fungicidal activity. Parietin targets the cell membrane and induces cell death via ROS-mediated lipid peroxidation after light irradiation. In summary, parietin exhibits light-enhanced fungicidal activity against all Candida species tested (including C. auris) and Cryptococcus neoformans, covering three of the four critical threats on the WHO's most recent fungal priority list.
Subject(s)
Antifungal Agents , Cryptococcus neoformans , Microbial Sensitivity Tests , Antifungal Agents/pharmacology , Cryptococcus neoformans/drug effects , Cryptococcus neoformans/radiation effects , Candida auris/drug effects , Light , Candida/drug effects , Reactive Oxygen Species/metabolism , Photochemotherapy/methods , Anthraquinones/pharmacology , Photosensitizing Agents/pharmacologyABSTRACT
Aim: To develop and evaluate chitosan-maleic acid conjugate. Methods: Maleic anhydride was attached to chitosan backbone via amide bond formation resulting in chitosan-maleic acid. After characterization of the product via 1H nuclear magnetic resonance, attenuated total reflectance-Fourier transform IR spectroscopy and 2,4,6-trinitrobenzenesulfonic acid assay, examination of mucoadhesion assessment was carried out. Results: The conjugate presented 44.91% modification and no toxicity could be observed after 1 day of incubation. Mucoadhesive properties exhibited 40.97-fold, 13.31-fold and 9.07-fold increase in elastic modulus, dynamic viscosity and viscous modulus, respectively. Moreover, detachment time was increased in 44.44-fold. Conclusion: Chitosan-maleic acid demonstrated enhanced in mucoadhesive properties resulting in biocompatibility. Therefore, potent candidates as polymeric excipients for oral drug delivery could be developed over corresponding chitosan.
