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

Author(s)

Sato, Mariana Rillo ; Oshiro-Junior, Joao Augusto ; Rodero, Camila Fernanda ; Boni, Fernanda Isadora ; Araujo, Victor Hugo Sousa ; Bauab, Tais Maria ; Nicholas, Dean ; Callan, John Francis ; Chorilli, Marlus

• Document type: Journal article
• Source: PHARMACEUTICALS; v. 16, n. 8, p. 12-pg., 2023-08-01.

Abstract

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 log10 for Hy.NLC-HG/PDT and 1.9 log10 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 (nonPDT) 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. (AU)

• FAPESP's process: 18/17573-7 - Potential effect of hypericin-loaded mucoadhesive nanostructured systems associated with antimicrobial photodynamic and sonodynamic therapies against Candida albicans strains
• Grantee: Mariana Rillo Sato
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 16/11198-4 - Nanostructured lipid carriers dispersed in situ gelling hydrogel for vaginal administration of hypericin associated with photodynamic therapy in the treatment of vulvovaginal candidiasis
• Grantee: Mariana Rillo Sato
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
• Grantee: Maria Vitória Lopes Badra Bentley
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/10261-2 - Evaluation of the potential of nanostructured lipid carriers for co-encapsulation of curcumin and fluconazole dispersed in thermally-responsive hydrogels in the treatment of vulvovaginal candidiasis
• Grantee: Victor Hugo Sousa Araujo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/17913-5 - Pharmacotechnical development and in vitro and in vivo anti-Candida albicans activity of nanostructured lipid carriers dispersed in hydrogels for vaginal administration of hypericin
• Grantee: Marlus Chorilli
• Support Opportunities: Regular Research Grants