Enhancing Antifungal Treatment of Candida albicans with Hypericin-Loaded Nanostructured Lipid Carriers in Hydrogels: Characterization, In Vitro, and In Vivo Photodynamic Evaluation

Mariana Rillo Sato, João Augusto Oshiro-Junior, Camila Fernanda Rodero, Fernanda Isadora Boni, Victor Hugo Sousa Araújo, Taís Maria Bauab, Dean Nicholas, John Francis Callan, Marlus Chorilli

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Background: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans, whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans-induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG). Methods: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated. Results: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans (p < 0.001) by 1.2 log 10 for Hy.NLC-HG/PDT and 1.9 log 10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group. Conclusions: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration.

Original languageEnglish
Article number1094
Number of pages1
Issue number8
Early online date1 Aug 2023
Publication statusPublished online - 1 Aug 2023

Bibliographical note

Funding Information:
This research was funded by the FAPESP (Sao Paulo Research Foundation, Brazil, Grant numbers #2016/11198-4, #2018/17573-7, #2019/10261-2, #2019/17913-5), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Finance Code 001), CNPq (National Council for Scientific and Technological Development, Brazil, Grant numer #408244/2018-6) and Ulster University. This study is part of the National Institute of Science and Technology in Pharmaceutical Nanotechnology: a transdisciplinary approach INCT-NANOFARMA, which is supported by FAPESP, Brazil, Grant #2014/50928-2, and by CNPq, Brazil, Grant #465687/2014-8.

Publisher Copyright:
© 2023 by the authors.


  • mucoadhesiveness
  • nanostructured system
  • photosensitizer
  • yeast
  • antifungal agent


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