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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICALS; v. 16, n. 8, p. 12-pg., 2023-08-01.

Resumo

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)

• Processo FAPESP: 18/17573-7 - Potencial efeito da hipericina incorporada em sistemas nanoestruturados mucoadesivos associados as terapias fotodinâmicas e sonodinâmicas antimicrobianas contra cepas de Candida albicans
• Beneficiário: Mariana Rillo Sato
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 16/11198-4 - Carreadores lipídicos nanoestruturados dispersos em hidrogéis de geleificação in situ para administração vaginal de hipericina associados à terapia fotodinâmica no tratamento da candidíase vulvovaginal
• Beneficiário: Mariana Rillo Sato
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/50928-2 - INCT 2014: Nanotecnologia Farmacêutica: uma abordagem transdisciplinar
• Beneficiário: Maria Vitória Lopes Badra Bentley
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/10261-2 - Avaliação do potencial de carreadores lipídicos nanoestruturados para co-encapsulação de curcumina e fluconazol dispersos em hidrogéis termorreponsivos no tratamento de candidíase vulvovaginal
• Beneficiário: Victor Hugo Sousa Araujo
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/17913-5 - Desenvolvimento farmacotécnico e atividade anti-Candida albicans in vitro e in vivo de carreadores lipídicos nanoestruturados dispersos em hidrogéis para administração vaginal de hipericina
• Beneficiário: Marlus Chorilli
• Modalidade de apoio: Auxílio à Pesquisa - Regular