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Photodynamic therapy-mediated hypericin-loaded nanostructured lipid carriers against vulvovaginal candidiasis
Authors:Mariana Rillo Sato  João Augusto Oshiro-Junior  Camila Fernanda Rodero  Fernanda Isadora Boni  Victor Hugo Sousa Araújo  Taís Maria Bauab  Dean Nicholas  John F Callan  Marlus Chorilli
Institution:1. School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo 14800-903, Brazil;2. Graduation Program in Pharmaceutical Sciences, State University of Paraíba, Campina Grande, Paraíba 58429-500, Brazil;3. Biomedical Sciences Research Institute, University of Ulster, Coleraine, Northern Ireland, United Kingdom;1. Clinic of Infectious Diseases, University of Bari, University Hospital Policlinico, Piazza Giulio Cesare n. 11, 70124 Bari Italy;2. Microbiology and Virology Unit, University of Bari, University Hospital Policlinico, Piazza Giulio Cesare n. 11, 70124 Bari Italy;1. Department of Bacteriology, University Hospital of Dijon, BP 37013, 21070 Dijon CEDEX, France;2. UMR/CNRS 6249 Chrono-environnement, University of Bourgogne-Franche-Comté, Besançon, France;3. Laboratoire de Parasitologie-Mycologie, Plateforme de Biologie Hospitalo-universitaire, 2 rue A. Ducoudray, BP 37013, 21070 Dijon Cedex, France;4. UMR PAM Univ Bourgogne Franche-Comté - AgroSup Dijon - Equipe Vin, Aliment, Microbiologie, Stress, 21078 Dijon, cedex, France;1. Uluda? University Faculty of Medicine, Department of Pulmonology, Bursa, Turkey;2. Uluda? University Faculty of Medicine, Department of Internal Medicine, Bursa, Turkey;3. Uluda? University Faculty of Medicine, Department of Hematology, Bursa, Turkey;4. Uluda? University Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Bursa, Turkey;5. Uluda? University Faculty of Medicine, Department of Microbiology, Bursa, Turkey;1. Department of Neurology, The Third affiliated Hospital of Sun Yat-sen University, Guangzhou, 510530, P. R. China;2. Department of Neurology, The First Affiliated Hospital of Guizhou University of traditional Chinese Medicine, Guiyang, 550001, P. R. China;3. Department of Medical Records, The Third affiliated Hospital of Sun Yat-sen University, Guangzhou, 510530, P. R. China;1. Dermatology and Venereology Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt;2. Microbiology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
Abstract:Introduction and Aim: The indiscriminate use and adverse effects of the main conventional antifungal agents compromise the effectiveness of treating vulvovaginal candidiasis (VVC), mainly caused by the species Candida albicans. This study evaluated the effectiveness of photodynamic therapy (PDT) and the in vitro and in vivo anti-candida potential of the hypericin (HYP)-loaded nanostructured lipid carriers (NLC). Materials and Methods: Empty NLC and NLC-HYP were characterized by the dynamic light scattering technique and transmission electron microscopy to evaluate the average particle size distribution and its morphologies. The in vitro inhibition photodynamic effect of the systems was tested to reduce the planktonic viability of C. albicans. The therapeutic assay photodynamic of the systems was performed to treat VVC in mice. Results: Empty NLC and NLC-HYP presented values of average hydrodynamic diameter, polydispersity index, and ζ-potential from 136 to 133 nm, 0.16 to 0.22, and -18 to -30 mV, respectively, on day 30. Microscopically, the systems showed spherical morphologies and nanoscale particles. Furthermore, in the in vitro inhibition assay, the treatment of PDT with NLC-HYP (NLC-HYP+) showed a significant reduction of the C. albicans planktonic viability compared to YNB negative control after 5 min of LED light irradiation. In the in vivo therapeutic assay, the antifungal group (vaginal antifungal cream) and NLC-HYP+ evaluated in the dark and by PDT, respectively, had a significant log10 reduction in fungal burden compared to the infected group on day 8 of the VVC treatment. Conclusion: Due to the in vitro and in vivo anti-candida potential, PDT-mediated systems can be an effective strategy in VVC therapy.
Keywords:Nanostructured lipid carriers  Hypericin  Antifungal activity  Photodynamic therapy  VVC  Vulvovaginal candidiasis  PDT  Photodynamic therapy  PS  Photosensitizer compound  HYP  Hypericin  DDS  Drug delivery systems  NLCs  Nanostructured lipid carriers  P40  Polyoxyethylene 40 stearate  CCAGT  Capric/caprylic acid triglycerides  HCO40  Ethoxylated hydrogenated castor oil 40  P407  Poloxamer 407  NTA  Nanoparticle tracking analysis  DLS  Dynamic light scattering  ELS  Electrophoretic light scattering  PDI  Polydispersity index  ZP  ζ-potential  SD  Standard deviation  TEM  Transmission electron microscopy  SOSG  Singlet oxygen generation  MIC  Minimum inhibitory concentration  YNB  Yeast nitrogen base  DMSO  Dimethyl sulfoxide  RB  Rosa bengal  SDA  Sabouraud dextrose agar  SDA+Clo  Sabouraud dextrose agar with chloramphenicol  MGG  May-Grünwald giemsa  CFU  Colony forming units  ?1  Colony forming units per mililiter
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