p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis

Detalhes bibliográficos
Autor(a) principal: Ferreira, P. S. [UNESP]
Data de Publicação: 2021
Outros Autores: Victorelli, F. D. [UNESP], Rodero, C. F. [UNESP], Fortunato, G. C. [UNESP], Araújo, V. H.S. [UNESP], Fonseca-Santos, B. [UNESP], Bauab, T. M. [UNESP], Van Dijck, P., Chorilli, M. [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.ijpharm.2021.120658
http://hdl.handle.net/11449/207737
Resumo: Vulvovaginal candidiasis (VVC) is an extremely common type of vaginal infection, which is mainly caused by Candida albicans. However, non-albicans Candida species are frequently more resistant to conventional antifungal agents and can represent up to 30% of cases. Due to side effects and increasing antifungal resistance presented by standard therapies, phenolic compounds, such as p-coumaric acid (p-CA), have been studied as molecules from natural sources with potential antifungal activity. p-CA is a poorly water-soluble compound, thus loading it into liquid crystals (LCs) may increase its solubility and effectiveness on the vaginal mucosa. Thereby, here we propose the development of mucoadhesive liquid crystalline systems with controlled release of p-CA, for the local treatment of VVC. Developed LCs consisted of fixed oily and aqueous phases (oleic acid and cholesterol (5:1) and poloxamer dispersion 16%, respectively), changing only the surfactant phase components (triethanolamine oleate (TEA-Oleate) or triethanolamine (TEA), the latter producing TEA-Oleate molecules when mixed with oleic acid). Systems were also diluted in artificial vaginal mucus (1:1 ratio) to mimic the vaginal environment and verify possible structural changes on formulations upon exposure to the mucosa. From the characterization assays, p-CA loaded TEA-Oleate systems presented mucoadhesive profile, liquid crystalline mesophases, well-organized structures and pseudoplastic behaviour, which are desirable parameters for topical formulations. Moreover, they were able to control the release of p-CA throughout the 12 h assay, as well as decrease its permeation into the vaginal mucosa. p-CA showed antifungal activity in vitro against reference strains of C. albicans (SC5314), C. glabrata (ATCC 2001) and C. krusei (ATCC 6258), and exhibited higher eradication of mature biofilms than amphotericin B and fluconazole. In vivo experiments demonstrated that the formulations reduced the presence of filamentous forms in the vaginal lavages and provided an improvement in swelling and redness present in the mice vaginal regions. Altogether, here we demonstrated the potential and feasibility of using p-CA loaded liquid crystalline systems as a mucoadhesive drug delivery system for topical treatment of VVC.
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spelling p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasisAnd biofilmCandida albicansCandida glabrataLiquid crystalline systemsP-coumaric acidVulvovaginal candidiasisVulvovaginal candidiasis (VVC) is an extremely common type of vaginal infection, which is mainly caused by Candida albicans. However, non-albicans Candida species are frequently more resistant to conventional antifungal agents and can represent up to 30% of cases. Due to side effects and increasing antifungal resistance presented by standard therapies, phenolic compounds, such as p-coumaric acid (p-CA), have been studied as molecules from natural sources with potential antifungal activity. p-CA is a poorly water-soluble compound, thus loading it into liquid crystals (LCs) may increase its solubility and effectiveness on the vaginal mucosa. Thereby, here we propose the development of mucoadhesive liquid crystalline systems with controlled release of p-CA, for the local treatment of VVC. Developed LCs consisted of fixed oily and aqueous phases (oleic acid and cholesterol (5:1) and poloxamer dispersion 16%, respectively), changing only the surfactant phase components (triethanolamine oleate (TEA-Oleate) or triethanolamine (TEA), the latter producing TEA-Oleate molecules when mixed with oleic acid). Systems were also diluted in artificial vaginal mucus (1:1 ratio) to mimic the vaginal environment and verify possible structural changes on formulations upon exposure to the mucosa. From the characterization assays, p-CA loaded TEA-Oleate systems presented mucoadhesive profile, liquid crystalline mesophases, well-organized structures and pseudoplastic behaviour, which are desirable parameters for topical formulations. Moreover, they were able to control the release of p-CA throughout the 12 h assay, as well as decrease its permeation into the vaginal mucosa. p-CA showed antifungal activity in vitro against reference strains of C. albicans (SC5314), C. glabrata (ATCC 2001) and C. krusei (ATCC 6258), and exhibited higher eradication of mature biofilms than amphotericin B and fluconazole. In vivo experiments demonstrated that the formulations reduced the presence of filamentous forms in the vaginal lavages and provided an improvement in swelling and redness present in the mice vaginal regions. Altogether, here we demonstrated the potential and feasibility of using p-CA loaded liquid crystalline systems as a mucoadhesive drug delivery system for topical treatment of VVC.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Department of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)Department of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP)Laboratory of Molecular Cell Biology Institute of Botany and Microbiology KU LeuvenVIB-KU Leuven Center for MicrobiologyDepartment of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)Department of Biological Sciences School of Pharmaceutical Sciences São Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)KU LeuvenVIB-KU Leuven Center for MicrobiologyFerreira, P. S. [UNESP]Victorelli, F. D. [UNESP]Rodero, C. F. [UNESP]Fortunato, G. C. [UNESP]Araújo, V. H.S. [UNESP]Fonseca-Santos, B. [UNESP]Bauab, T. M. [UNESP]Van Dijck, P.Chorilli, M. [UNESP]2021-06-25T11:00:10Z2021-06-25T11:00:10Z2021-06-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.ijpharm.2021.120658International Journal of Pharmaceutics, v. 603.1873-34760378-5173http://hdl.handle.net/11449/20773710.1016/j.ijpharm.2021.1206582-s2.0-85105870194Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Pharmaceuticsinfo:eu-repo/semantics/openAccess2024-06-24T13:46:34Zoai:repositorio.unesp.br:11449/207737Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T23:46:22.537634Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis
title p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis
spellingShingle p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis
Ferreira, P. S. [UNESP]
And biofilm
Candida albicans
Candida glabrata
Liquid crystalline systems
P-coumaric acid
Vulvovaginal candidiasis
title_short p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis
title_full p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis
title_fullStr p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis
title_full_unstemmed p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis
title_sort p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis
author Ferreira, P. S. [UNESP]
author_facet Ferreira, P. S. [UNESP]
Victorelli, F. D. [UNESP]
Rodero, C. F. [UNESP]
Fortunato, G. C. [UNESP]
Araújo, V. H.S. [UNESP]
Fonseca-Santos, B. [UNESP]
Bauab, T. M. [UNESP]
Van Dijck, P.
Chorilli, M. [UNESP]
author_role author
author2 Victorelli, F. D. [UNESP]
Rodero, C. F. [UNESP]
Fortunato, G. C. [UNESP]
Araújo, V. H.S. [UNESP]
Fonseca-Santos, B. [UNESP]
Bauab, T. M. [UNESP]
Van Dijck, P.
Chorilli, M. [UNESP]
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
KU Leuven
VIB-KU Leuven Center for Microbiology
dc.contributor.author.fl_str_mv Ferreira, P. S. [UNESP]
Victorelli, F. D. [UNESP]
Rodero, C. F. [UNESP]
Fortunato, G. C. [UNESP]
Araújo, V. H.S. [UNESP]
Fonseca-Santos, B. [UNESP]
Bauab, T. M. [UNESP]
Van Dijck, P.
Chorilli, M. [UNESP]
dc.subject.por.fl_str_mv And biofilm
Candida albicans
Candida glabrata
Liquid crystalline systems
P-coumaric acid
Vulvovaginal candidiasis
topic And biofilm
Candida albicans
Candida glabrata
Liquid crystalline systems
P-coumaric acid
Vulvovaginal candidiasis
description Vulvovaginal candidiasis (VVC) is an extremely common type of vaginal infection, which is mainly caused by Candida albicans. However, non-albicans Candida species are frequently more resistant to conventional antifungal agents and can represent up to 30% of cases. Due to side effects and increasing antifungal resistance presented by standard therapies, phenolic compounds, such as p-coumaric acid (p-CA), have been studied as molecules from natural sources with potential antifungal activity. p-CA is a poorly water-soluble compound, thus loading it into liquid crystals (LCs) may increase its solubility and effectiveness on the vaginal mucosa. Thereby, here we propose the development of mucoadhesive liquid crystalline systems with controlled release of p-CA, for the local treatment of VVC. Developed LCs consisted of fixed oily and aqueous phases (oleic acid and cholesterol (5:1) and poloxamer dispersion 16%, respectively), changing only the surfactant phase components (triethanolamine oleate (TEA-Oleate) or triethanolamine (TEA), the latter producing TEA-Oleate molecules when mixed with oleic acid). Systems were also diluted in artificial vaginal mucus (1:1 ratio) to mimic the vaginal environment and verify possible structural changes on formulations upon exposure to the mucosa. From the characterization assays, p-CA loaded TEA-Oleate systems presented mucoadhesive profile, liquid crystalline mesophases, well-organized structures and pseudoplastic behaviour, which are desirable parameters for topical formulations. Moreover, they were able to control the release of p-CA throughout the 12 h assay, as well as decrease its permeation into the vaginal mucosa. p-CA showed antifungal activity in vitro against reference strains of C. albicans (SC5314), C. glabrata (ATCC 2001) and C. krusei (ATCC 6258), and exhibited higher eradication of mature biofilms than amphotericin B and fluconazole. In vivo experiments demonstrated that the formulations reduced the presence of filamentous forms in the vaginal lavages and provided an improvement in swelling and redness present in the mice vaginal regions. Altogether, here we demonstrated the potential and feasibility of using p-CA loaded liquid crystalline systems as a mucoadhesive drug delivery system for topical treatment of VVC.
publishDate 2021
dc.date.none.fl_str_mv 2021-06-25T11:00:10Z
2021-06-25T11:00:10Z
2021-06-15
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/10.1016/j.ijpharm.2021.120658
International Journal of Pharmaceutics, v. 603.
1873-3476
0378-5173
http://hdl.handle.net/11449/207737
10.1016/j.ijpharm.2021.120658
2-s2.0-85105870194
url http://dx.doi.org/10.1016/j.ijpharm.2021.120658
http://hdl.handle.net/11449/207737
identifier_str_mv International Journal of Pharmaceutics, v. 603.
1873-3476
0378-5173
10.1016/j.ijpharm.2021.120658
2-s2.0-85105870194
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv International Journal of Pharmaceutics
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)
repository.mail.fl_str_mv
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