Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations

Detalhes bibliográficos
Autor(a) principal: Costa-Orlandi, Caroline Barcelos [UNESP]
Data de Publicação: 2020
Outros Autores: Serafim-Pinto, Aline [UNESP], da Silva, Patrícia Bento [UNESP], Bila, Níura Madalena [UNESP], Bonatti, Jean Lucas de Carvalho [UNESP], Scorzoni, Liliana [UNESP], Singulani, Junya de Lacorte [UNESP], Santos, Claudia Tavares dos [UNESP], Nazaré, Ana Carolina [UNESP], Chorilli, Marlus [UNESP], Regasini, Luis Octávio [UNESP], Fusco-Almeida, Ana Marisa [UNESP], Mendes-Giannini, Maria José Soares [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3389/fmicb.2020.01154
http://hdl.handle.net/11449/200650
Resumo: Dermatophytosis is the most common mycosis worldwide, affecting approximately 20 to 25% of the population, regardless of gender, race, color, and age. Most antifungal agents used for the treatment of dermatophytosis belong to the azole and allylamine classes. Dermatophytes are reported to be resistant to most commercial drugs, especially microbial biofilms, in addition to their considerable toxicity. It should be emphasized the importance of looking for new molecules with reduced toxicity, as well as new targets and mechanisms of action. This work aims to incorporate nonyl 3,4-dihydroxybenzoate, a potent fungicide compound against planktonic cells and dermatophyte biofilms in nanostructured lipid systems (NLS), in order to reduce toxicity in high concentrations, improve its solubility and maintain its effectiveness. The compound was incorporated into NLS constituted by cholesterol, mixture of polyoxyethylene (23) lauryl ether (Brij®98) and soybean phosphatidylcholine (Epikuron® 200)], 2: 1 ratio and PBS (phosphate-buffered saline). The characterization of the incorporation was performed. Susceptibility tests were conducted according to document M38-A2 by CLSI (2008). The toxicity of the NLS compound was evaluated in HaCaT cell lines by the sulforhodamine B method and in alternative models Caenorhabditis elegans and zebrafish. Finally, its efficacy was evaluated against the mature Trichophyton rubrum and Trichophyton mentagrophytes biofilms. NLS and nonyl 3,4-dihydroxybenzoate loaded into NLS displayed sizes ranging from 137.8 ± 1.815 to 167.9 ± 4.070 nm; the polydispersity index (PDI) varying from 0.331 ± 0.020 to 0.377 ± 0.004 and zeta potential ranging from −1.46 ± 0.157 to −4.63 ± 0.398 mV, respectively. Polarized light microscopy results confirmed the formation of NLS of the microemulsion type. Nonyl incorporated into NLS showed minimum inhibitory concentration (MIC) values, ranging from 2 to 15.6 mg/L. The toxicity tests presented cell viability highers than 80% in all tested concentrations, as well as, a significantly increased of the survival of Caenorhabditis elegans and zebrafish models. Anti-biofilm tests proved the efficacy of the incorporation. These findings contribute significantly to the search for new antifungals and allow the systemic administration of the compound, since the incorporation can increase the solubility of non-polar compounds, improve bioavailability, effectiveness and reduce toxicity.
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spelling Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrationsalternative modelsbiofilmsCaenorhabditis elegansdermatophytesnanoparticlesTrichophyton mentagrophytesTrichophyton rubrumzebrafishDermatophytosis is the most common mycosis worldwide, affecting approximately 20 to 25% of the population, regardless of gender, race, color, and age. Most antifungal agents used for the treatment of dermatophytosis belong to the azole and allylamine classes. Dermatophytes are reported to be resistant to most commercial drugs, especially microbial biofilms, in addition to their considerable toxicity. It should be emphasized the importance of looking for new molecules with reduced toxicity, as well as new targets and mechanisms of action. This work aims to incorporate nonyl 3,4-dihydroxybenzoate, a potent fungicide compound against planktonic cells and dermatophyte biofilms in nanostructured lipid systems (NLS), in order to reduce toxicity in high concentrations, improve its solubility and maintain its effectiveness. The compound was incorporated into NLS constituted by cholesterol, mixture of polyoxyethylene (23) lauryl ether (Brij®98) and soybean phosphatidylcholine (Epikuron® 200)], 2: 1 ratio and PBS (phosphate-buffered saline). The characterization of the incorporation was performed. Susceptibility tests were conducted according to document M38-A2 by CLSI (2008). The toxicity of the NLS compound was evaluated in HaCaT cell lines by the sulforhodamine B method and in alternative models Caenorhabditis elegans and zebrafish. Finally, its efficacy was evaluated against the mature Trichophyton rubrum and Trichophyton mentagrophytes biofilms. NLS and nonyl 3,4-dihydroxybenzoate loaded into NLS displayed sizes ranging from 137.8 ± 1.815 to 167.9 ± 4.070 nm; the polydispersity index (PDI) varying from 0.331 ± 0.020 to 0.377 ± 0.004 and zeta potential ranging from −1.46 ± 0.157 to −4.63 ± 0.398 mV, respectively. Polarized light microscopy results confirmed the formation of NLS of the microemulsion type. Nonyl incorporated into NLS showed minimum inhibitory concentration (MIC) values, ranging from 2 to 15.6 mg/L. The toxicity tests presented cell viability highers than 80% in all tested concentrations, as well as, a significantly increased of the survival of Caenorhabditis elegans and zebrafish models. Anti-biofilm tests proved the efficacy of the incorporation. These findings contribute significantly to the search for new antifungals and allow the systemic administration of the compound, since the incorporation can increase the solubility of non-polar compounds, improve bioavailability, effectiveness and reduce toxicity.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)School of Pharmaceutical Sciences Department of Clinical Analysis Universidade Estadual Paulista (UNESP)School of Pharmaceutical Sciences Department of Drugs and Medicines Universidade Estadual Paulista (UNESP)Universidade Eduardo Mondlane School of VeterinaryInstitute of Biosciences Humanities and Exact Sciences Department of Chemistry and Environmental Sciences Universidade Estadual Paulista (UNESP)School of Pharmaceutical Sciences Department of Clinical Analysis Universidade Estadual Paulista (UNESP)School of Pharmaceutical Sciences Department of Drugs and Medicines Universidade Estadual Paulista (UNESP)Institute of Biosciences Humanities and Exact Sciences Department of Chemistry and Environmental Sciences Universidade Estadual Paulista (UNESP)FAPESP: 2018/02785-9Universidade Estadual Paulista (Unesp)School of VeterinaryCosta-Orlandi, Caroline Barcelos [UNESP]Serafim-Pinto, Aline [UNESP]da Silva, Patrícia Bento [UNESP]Bila, Níura Madalena [UNESP]Bonatti, Jean Lucas de Carvalho [UNESP]Scorzoni, Liliana [UNESP]Singulani, Junya de Lacorte [UNESP]Santos, Claudia Tavares dos [UNESP]Nazaré, Ana Carolina [UNESP]Chorilli, Marlus [UNESP]Regasini, Luis Octávio [UNESP]Fusco-Almeida, Ana Marisa [UNESP]Mendes-Giannini, Maria José Soares [UNESP]2020-12-12T02:12:25Z2020-12-12T02:12:25Z2020-06-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fmicb.2020.01154Frontiers in Microbiology, v. 11.1664-302Xhttp://hdl.handle.net/11449/20065010.3389/fmicb.2020.011542-s2.0-85087018800Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Microbiologyinfo:eu-repo/semantics/openAccess2024-06-24T13:45:28Zoai:repositorio.unesp.br:11449/200650Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:05:01.305120Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations
title Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations
spellingShingle Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations
Costa-Orlandi, Caroline Barcelos [UNESP]
alternative models
biofilms
Caenorhabditis elegans
dermatophytes
nanoparticles
Trichophyton mentagrophytes
Trichophyton rubrum
zebrafish
title_short Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations
title_full Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations
title_fullStr Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations
title_full_unstemmed Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations
title_sort Incorporation of Nonyl 3,4-Dihydroxybenzoate Into Nanostructured Lipid Systems: Effective Alternative for Maintaining Anti-Dermatophytic and Antibiofilm Activities and Reducing Toxicity at High Concentrations
author Costa-Orlandi, Caroline Barcelos [UNESP]
author_facet Costa-Orlandi, Caroline Barcelos [UNESP]
Serafim-Pinto, Aline [UNESP]
da Silva, Patrícia Bento [UNESP]
Bila, Níura Madalena [UNESP]
Bonatti, Jean Lucas de Carvalho [UNESP]
Scorzoni, Liliana [UNESP]
Singulani, Junya de Lacorte [UNESP]
Santos, Claudia Tavares dos [UNESP]
Nazaré, Ana Carolina [UNESP]
Chorilli, Marlus [UNESP]
Regasini, Luis Octávio [UNESP]
Fusco-Almeida, Ana Marisa [UNESP]
Mendes-Giannini, Maria José Soares [UNESP]
author_role author
author2 Serafim-Pinto, Aline [UNESP]
da Silva, Patrícia Bento [UNESP]
Bila, Níura Madalena [UNESP]
Bonatti, Jean Lucas de Carvalho [UNESP]
Scorzoni, Liliana [UNESP]
Singulani, Junya de Lacorte [UNESP]
Santos, Claudia Tavares dos [UNESP]
Nazaré, Ana Carolina [UNESP]
Chorilli, Marlus [UNESP]
Regasini, Luis Octávio [UNESP]
Fusco-Almeida, Ana Marisa [UNESP]
Mendes-Giannini, Maria José Soares [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
School of Veterinary
dc.contributor.author.fl_str_mv Costa-Orlandi, Caroline Barcelos [UNESP]
Serafim-Pinto, Aline [UNESP]
da Silva, Patrícia Bento [UNESP]
Bila, Níura Madalena [UNESP]
Bonatti, Jean Lucas de Carvalho [UNESP]
Scorzoni, Liliana [UNESP]
Singulani, Junya de Lacorte [UNESP]
Santos, Claudia Tavares dos [UNESP]
Nazaré, Ana Carolina [UNESP]
Chorilli, Marlus [UNESP]
Regasini, Luis Octávio [UNESP]
Fusco-Almeida, Ana Marisa [UNESP]
Mendes-Giannini, Maria José Soares [UNESP]
dc.subject.por.fl_str_mv alternative models
biofilms
Caenorhabditis elegans
dermatophytes
nanoparticles
Trichophyton mentagrophytes
Trichophyton rubrum
zebrafish
topic alternative models
biofilms
Caenorhabditis elegans
dermatophytes
nanoparticles
Trichophyton mentagrophytes
Trichophyton rubrum
zebrafish
description Dermatophytosis is the most common mycosis worldwide, affecting approximately 20 to 25% of the population, regardless of gender, race, color, and age. Most antifungal agents used for the treatment of dermatophytosis belong to the azole and allylamine classes. Dermatophytes are reported to be resistant to most commercial drugs, especially microbial biofilms, in addition to their considerable toxicity. It should be emphasized the importance of looking for new molecules with reduced toxicity, as well as new targets and mechanisms of action. This work aims to incorporate nonyl 3,4-dihydroxybenzoate, a potent fungicide compound against planktonic cells and dermatophyte biofilms in nanostructured lipid systems (NLS), in order to reduce toxicity in high concentrations, improve its solubility and maintain its effectiveness. The compound was incorporated into NLS constituted by cholesterol, mixture of polyoxyethylene (23) lauryl ether (Brij®98) and soybean phosphatidylcholine (Epikuron® 200)], 2: 1 ratio and PBS (phosphate-buffered saline). The characterization of the incorporation was performed. Susceptibility tests were conducted according to document M38-A2 by CLSI (2008). The toxicity of the NLS compound was evaluated in HaCaT cell lines by the sulforhodamine B method and in alternative models Caenorhabditis elegans and zebrafish. Finally, its efficacy was evaluated against the mature Trichophyton rubrum and Trichophyton mentagrophytes biofilms. NLS and nonyl 3,4-dihydroxybenzoate loaded into NLS displayed sizes ranging from 137.8 ± 1.815 to 167.9 ± 4.070 nm; the polydispersity index (PDI) varying from 0.331 ± 0.020 to 0.377 ± 0.004 and zeta potential ranging from −1.46 ± 0.157 to −4.63 ± 0.398 mV, respectively. Polarized light microscopy results confirmed the formation of NLS of the microemulsion type. Nonyl incorporated into NLS showed minimum inhibitory concentration (MIC) values, ranging from 2 to 15.6 mg/L. The toxicity tests presented cell viability highers than 80% in all tested concentrations, as well as, a significantly increased of the survival of Caenorhabditis elegans and zebrafish models. Anti-biofilm tests proved the efficacy of the incorporation. These findings contribute significantly to the search for new antifungals and allow the systemic administration of the compound, since the incorporation can increase the solubility of non-polar compounds, improve bioavailability, effectiveness and reduce toxicity.
publishDate 2020
dc.date.none.fl_str_mv 2020-12-12T02:12:25Z
2020-12-12T02:12:25Z
2020-06-05
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3389/fmicb.2020.01154
Frontiers in Microbiology, v. 11.
1664-302X
http://hdl.handle.net/11449/200650
10.3389/fmicb.2020.01154
2-s2.0-85087018800
url http://dx.doi.org/10.3389/fmicb.2020.01154
http://hdl.handle.net/11449/200650
identifier_str_mv Frontiers in Microbiology, v. 11.
1664-302X
10.3389/fmicb.2020.01154
2-s2.0-85087018800
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers in Microbiology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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