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

doi:10.3390/ph16081094

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

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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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 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 language	English
Article number	1094
Number of pages	1
Journal	Pharmaceuticals
Volume	16
Issue number	8
Early online date	1 Aug 2023
DOIs	https://doi.org/10.3390/ph16081094
Publication status	Published 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.

Keywords

mucoadhesiveness
nanostructured system
photosensitizer
yeast
antifungal agent

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ph16081094

pharmaceuticals-16-01094Final published version, 2.17 MBLicence: CC BY

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Sato, M. R., Oshiro-Junior, J. A., Rodero, C. F., Boni, F. I., Araújo, V. H. S., Bauab, T. M., Nicholas, D., Callan, J. F., & Chorilli, M. (2023). Enhancing Antifungal Treatment of Candida albicans with Hypericin-Loaded Nanostructured Lipid Carriers in Hydrogels: Characterization, In Vitro, and In Vivo Photodynamic Evaluation. Pharmaceuticals, 16(8), Article 1094. Advance online publication. https://doi.org/10.3390/ph16081094

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

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 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.",

keywords = "mucoadhesiveness, nanostructured system, photosensitizer, yeast, antifungal agent",

author = "Sato, {Mariana Rillo} and Oshiro-Junior, {Jo{\~a}o Augusto} and Rodero, {Camila Fernanda} and Boni, {Fernanda Isadora} and Ara{\'u}jo, {Victor Hugo Sousa} and Bauab, {Ta{\'i}s Maria} and Dean Nicholas and Callan, {John Francis} and Marlus Chorilli",

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 (Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de N{\'i}vel 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: {\textcopyright} 2023 by the authors.",

year = "2023",

month = aug,

day = "1",

doi = "10.3390/ph16081094",

language = "English",

volume = "16",

journal = "Pharmaceuticals",

issn = "1424-8247",

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Sato, MR, Oshiro-Junior, JA, Rodero, CF, Boni, FI, Araújo, VHS, Bauab, TM, Nicholas, D, Callan, JF & Chorilli, M 2023, 'Enhancing Antifungal Treatment of Candida albicans with Hypericin-Loaded Nanostructured Lipid Carriers in Hydrogels: Characterization, In Vitro, and In Vivo Photodynamic Evaluation', Pharmaceuticals, vol. 16, no. 8, 1094. https://doi.org/10.3390/ph16081094

Enhancing Antifungal Treatment of Candida albicans with Hypericin-Loaded Nanostructured Lipid Carriers in Hydrogels: Characterization, In Vitro, and In Vivo Photodynamic Evaluation. / Sato, Mariana Rillo; Oshiro-Junior, João Augusto; Rodero, Camila Fernanda et al.
In: Pharmaceuticals, Vol. 16, No. 8, 1094, 01.08.2023.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Enhancing Antifungal Treatment of Candida albicans with Hypericin-Loaded Nanostructured Lipid Carriers in Hydrogels: Characterization, In Vitro, and In Vivo Photodynamic Evaluation

AU - Sato, Mariana Rillo

AU - Oshiro-Junior, João Augusto

AU - Rodero, Camila Fernanda

AU - Boni, Fernanda Isadora

AU - Araújo, Victor Hugo Sousa

AU - Bauab, Taís Maria

AU - Nicholas, Dean

AU - Callan, John Francis

AU - Chorilli, Marlus

N1 - 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.

PY - 2023/8/1

Y1 - 2023/8/1

N2 - 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.

AB - 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.

KW - mucoadhesiveness

KW - nanostructured system

KW - photosensitizer

KW - yeast

KW - antifungal agent

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U2 - 10.3390/ph16081094

DO - 10.3390/ph16081094

M3 - Article

C2 - 37631009

SN - 1424-8247

VL - 16

JO - Pharmaceuticals

JF - Pharmaceuticals

IS - 8

M1 - 1094

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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