Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.

Detalhes bibliográficos
Autor(a) principal: Pittol, Vanessa
Data de Publicação: 2022
Outros Autores: Veras, Kleyton Santos, Kaiser, Samuel, Danielli, Letícia Jacobi, Fuentefria, Alexandre Meneghello, Ortega , George González
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Brazilian Journal of Pharmaceutical Sciences
Texto Completo: https://www.revistas.usp.br/bjps/article/view/204229
Resumo: Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.
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spelling Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.GriseofulvinPoloxamer 407Micellar solubilizationDrug-polymer interactionAntifungal activityPoorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2022-11-23info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/20422910.1590/s2175-97902022e19731 Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)2175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/204229/194791Copyright (c) 2022 Brazilian Journal of Pharmaceutical Scienceshttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessPittol, VanessaVeras, Kleyton SantosKaiser, SamuelDanielli, Letícia JacobiFuentefria, Alexandre MeneghelloOrtega , George González2023-06-05T14:20:58Zoai:revistas.usp.br:article/204229Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2023-06-05T14:20:58Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false
dc.title.none.fl_str_mv Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.
title Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.
spellingShingle Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.
Pittol, Vanessa
Griseofulvin
Poloxamer 407
Micellar solubilization
Drug-polymer interaction
Antifungal activity
title_short Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.
title_full Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.
title_fullStr Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.
title_full_unstemmed Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.
title_sort Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp.
author Pittol, Vanessa
author_facet Pittol, Vanessa
Veras, Kleyton Santos
Kaiser, Samuel
Danielli, Letícia Jacobi
Fuentefria, Alexandre Meneghello
Ortega , George González
author_role author
author2 Veras, Kleyton Santos
Kaiser, Samuel
Danielli, Letícia Jacobi
Fuentefria, Alexandre Meneghello
Ortega , George González
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Pittol, Vanessa
Veras, Kleyton Santos
Kaiser, Samuel
Danielli, Letícia Jacobi
Fuentefria, Alexandre Meneghello
Ortega , George González
dc.subject.por.fl_str_mv Griseofulvin
Poloxamer 407
Micellar solubilization
Drug-polymer interaction
Antifungal activity
topic Griseofulvin
Poloxamer 407
Micellar solubilization
Drug-polymer interaction
Antifungal activity
description Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.
publishDate 2022
dc.date.none.fl_str_mv 2022-11-23
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://www.revistas.usp.br/bjps/article/view/204229
10.1590/s2175-97902022e19731
url https://www.revistas.usp.br/bjps/article/view/204229
identifier_str_mv 10.1590/s2175-97902022e19731
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://www.revistas.usp.br/bjps/article/view/204229/194791
dc.rights.driver.fl_str_mv Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Copyright (c) 2022 Brazilian Journal of Pharmaceutical Sciences
https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
publisher.none.fl_str_mv Universidade de São Paulo. Faculdade de Ciências Farmacêuticas
dc.source.none.fl_str_mv Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)
Brazilian Journal of Pharmaceutical Sciences; v. 58 (2022)
Brazilian Journal of Pharmaceutical Sciences; Vol. 58 (2022)
2175-9790
1984-8250
reponame:Brazilian Journal of Pharmaceutical Sciences
instname:Universidade de São Paulo (USP)
instacron:USP
instname_str Universidade de São Paulo (USP)
instacron_str USP
institution USP
reponame_str Brazilian Journal of Pharmaceutical Sciences
collection Brazilian Journal of Pharmaceutical Sciences
repository.name.fl_str_mv Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)
repository.mail.fl_str_mv bjps@usp.br||elizabeth.igne@gmail.com
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