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

• Published in: Pharmaceuticals (Basel, Switzerland) Switzerland), 2023-08, Vol.16 (8)
• Main Authors: Sato, Mariana Rillo, Oshiro-Junior, João Augusto, Rodero, Camila Fernanda, Boni, Fernanda Isadora, Araújo, Victor Hugo Sousa, Bauab, Taís Maria, Nicholas, Dean, Callan, John Francis, Chorilli, Marlus
• Format: Article
• Language: English
• Subjects: Candidiasis; Dosage and administration; Drug therapy; Gels (Pharmacy); Hypericin; Lipids; Materials; Nanomedicine; Structure; Testing
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph16081094

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[sub.10] for Hy.NLC-HG/PDT and 1.9 log[sub.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.