Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20270 |
Resumo: | Superficial mycoses are fungal diseases caused on skin, hair and nails and are among the infectious diseases with the highest incidence and difficult to treat, making them a serious public health problem. The purpose of this study was the development of nanotechnological based formulations, contemplating the use of vegetable lipids for topical application of tioconazole, aiming the treatment of superficial mycoses.The first part of this work was focused on the development of hydrogels containing Mangospheres (lipid nanoparticles prepared with mango butter, meleuca oil and tioconazole at 2 mg/mL), and hydrogels containing tioconazoleloaded copaiba oil polymeric nanocapsules, coated and uncoated with chitosan (1 mg/mL). Mangospheres were prepared by high-pressure homogenization technique and the polymeric nanocapsules by interfacial deposition of pre-formed polymer method. The nanoparticles showed adequate physicochemical characteristics. The mean particle size was around 100 nm for Mangospheres and 170 nm for copaiba oil nanocapsules. The formulations showed the polydispersity index below 0.15, slightly acid pH and negative zeta potential for Mangospheres and uncoated nanocapsules and positive for chitosan-coated nanocapasules. Tioconazole content was 1.64-1.74 mg/mL for Mangospheres and 1.00 mg/mL for copaiba nanocapsules. The formulations presented antifungal activity and a great control of tioconazole release was observed for Mangospheres containing melaleuca oil and for the uncoated nanocapsules. The nanostructures were preserved after incorporation into hydrogels. The hydrogels showed slightly acidic pH, drug content close to the theoretical values and flow characteristics in accordance with Casson model for hydrogels containing Mangopheres. The hydrogels containing the cationiccoated polymeric nanocapsules presented Hershel-Bulkley flow model and bioadhesivity. In vitro skin permeation studies showed tioconazole targeting to stratum corneum for the hydrogels presenting Mangospheres and copaiba oil nanocapsules, with greater retention for the hydrogels containing the coated copaiba oil nanocapsules. The second part of the present work focused on studies related to the optimization of formulations for the treatment of onychomycosis, starting with a review of the literature on the use of essential oils in treating these infections. In addition, it was aimed to develop a nail formulation containing tioconazole associated with nanocapsules of medium chain triglycerides coated with chitosan. The coated and uncoated nanocapsules were obtained by interfacial deposition of pre-formed polymer and showed nanometric size, adequate polydispersity index and positive zeta potential for the coated nanocapsules and negative for the uncoated particles. Tioconazole content was 1.00 mg/mL and pH with slightly acid values. Both formulations showed control of tioconazole release and antifungal activity. The nail formulation showed adequate characteristics for nail application and preserved the nanostructures while on nail permeation studies, presented higher percentage of tioconazole recovery from nail plate. Confocal microscopy analysis showed more than 30% of nail thickness in penetration depth of the fluorescent marker form the formulations. In an ex vivo onychomycosis model, the ungual formulations showed equivalent activity compared to the commercial tioconazole formulation with tioconazole concentration of 280 times lower. In addition, the association of tioconazole to polymeric nanocapsules led to a reduction of the irritative potential of the drug in vitro. |
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Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiaisInnovative nanotechnological formulations for topical treatment of superficial mycosisTioconazolNanopartículas lipídicasNanocápsulas poliméricasMatérias-primas vegetaisMicoses superficiaisPenetração cutâneaOnicomicosesPenetração unguealTioconazoleLipid nanocparticlesPolymeric nanocapsulesNatural raw materialsSuperficial mycosisSkin penetrationOnychomycosisNail penetrationCNPQ::CIENCIAS DA SAUDE::FARMACIASuperficial mycoses are fungal diseases caused on skin, hair and nails and are among the infectious diseases with the highest incidence and difficult to treat, making them a serious public health problem. The purpose of this study was the development of nanotechnological based formulations, contemplating the use of vegetable lipids for topical application of tioconazole, aiming the treatment of superficial mycoses.The first part of this work was focused on the development of hydrogels containing Mangospheres (lipid nanoparticles prepared with mango butter, meleuca oil and tioconazole at 2 mg/mL), and hydrogels containing tioconazoleloaded copaiba oil polymeric nanocapsules, coated and uncoated with chitosan (1 mg/mL). Mangospheres were prepared by high-pressure homogenization technique and the polymeric nanocapsules by interfacial deposition of pre-formed polymer method. The nanoparticles showed adequate physicochemical characteristics. The mean particle size was around 100 nm for Mangospheres and 170 nm for copaiba oil nanocapsules. The formulations showed the polydispersity index below 0.15, slightly acid pH and negative zeta potential for Mangospheres and uncoated nanocapsules and positive for chitosan-coated nanocapasules. Tioconazole content was 1.64-1.74 mg/mL for Mangospheres and 1.00 mg/mL for copaiba nanocapsules. The formulations presented antifungal activity and a great control of tioconazole release was observed for Mangospheres containing melaleuca oil and for the uncoated nanocapsules. The nanostructures were preserved after incorporation into hydrogels. The hydrogels showed slightly acidic pH, drug content close to the theoretical values and flow characteristics in accordance with Casson model for hydrogels containing Mangopheres. The hydrogels containing the cationiccoated polymeric nanocapsules presented Hershel-Bulkley flow model and bioadhesivity. In vitro skin permeation studies showed tioconazole targeting to stratum corneum for the hydrogels presenting Mangospheres and copaiba oil nanocapsules, with greater retention for the hydrogels containing the coated copaiba oil nanocapsules. The second part of the present work focused on studies related to the optimization of formulations for the treatment of onychomycosis, starting with a review of the literature on the use of essential oils in treating these infections. In addition, it was aimed to develop a nail formulation containing tioconazole associated with nanocapsules of medium chain triglycerides coated with chitosan. The coated and uncoated nanocapsules were obtained by interfacial deposition of pre-formed polymer and showed nanometric size, adequate polydispersity index and positive zeta potential for the coated nanocapsules and negative for the uncoated particles. Tioconazole content was 1.00 mg/mL and pH with slightly acid values. Both formulations showed control of tioconazole release and antifungal activity. The nail formulation showed adequate characteristics for nail application and preserved the nanostructures while on nail permeation studies, presented higher percentage of tioconazole recovery from nail plate. Confocal microscopy analysis showed more than 30% of nail thickness in penetration depth of the fluorescent marker form the formulations. In an ex vivo onychomycosis model, the ungual formulations showed equivalent activity compared to the commercial tioconazole formulation with tioconazole concentration of 280 times lower. In addition, the association of tioconazole to polymeric nanocapsules led to a reduction of the irritative potential of the drug in vitro.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESMicoses superficiais são doenças fúngicas ocasionadas na pele, pelos e unhas e se encontram entre as doenças infecciosas de maior incidência e difícil tratamento, o que as torna um sério problema de saúde pública. O objetivo deste trabalho foi o desenvolvimento de formulações de base nanotecnológica, contemplando a utilização de lipídeos vegetais para a aplicação tópica de tioconazol visando o tratamento de micoses superficiais. Na primeira parte do estudo, focou-se no desenvolvimento de hidrogéis contendo Mangosferas (nanopartículas lipídicas preparadas com manteiga de manga, óleo de melaleuca e tioconazol a 2 mg/mL), as quais foram preparadas pelo método de homogeneização a alta pressão, e também, hidrogéis contendo nanocápsulas poliméricas de óleo de copaíba, revestidas e não revestidas com quitosana com tioconazol a 1 mg/mL, obtidas por deposição interfacial do polímero pré-formado. As nanopartículas apresentaram características satisfatórias com tamanho de partícula em torno de 100 nm para as Mangoesferas e 170 nm para as nanocápsulas poliméricas; o índice de polidispersão abaixo de 0,15 para ambas; pH ligeiramente ácido; potencial zeta negativo para as Mangoesferas e nanocápsulas sem revestimento e positivo para as nanocápsulas revestidas com quitosana. O teor de tioconazol foi de 1,64-1,74 mg/mL para as Mangoesferas e 1,00 mg/mL para as nanocápsulas de copaíba. As formulações apresentaram atividade antifúngica e o controle de liberação do tioconazol foi mais pronunciado para as Mangoesferas contendo o óleo de melaleuca e para as nanocápsulas não revestidas. Após a incorporação nos hidrogéis, as nanoestruturas foram preservadas. Os hidrogéis apresentaram pH ligeiramente ácido, teor de fármaco próximo ao teórico e características de fluxo de acordo com o modelo de Casson para os hidrogéis contendo as Mangoesferas. Os hidrogéis contendo as nanocápsulas poliméricas revestidas com quitosana apresentaram modelo de fluxo do tipo Hershel-Bulkley e bioadesividade. No estudo de permeação cutânea in vitro, os hidrogéis contendo as Mangoesferas e as nanocápsulas de copaíba direcionaram o tioconazol para o estrato córneo, com maior retenção para os hidrogéis contendo as nanocápsulas de copaíba revestidas. A segunda estapa deste trabalho concentrou nos estudos relacionados à otimização de formulações para o tratamento de onicomicoses, inciando com uma revisão da literatura sobre a utilização de óleos essenciais no tratamento destas infecções. Além disso, objetivou-se desenvolver uma formulação ungueal contendo tioconazol associado à nanocápsulas de triglicerídeos de cadeia média revestidas com quitosana. As nanocápsulas revestidas e não revestidas foram preparadas por deposição interfacial do polímero pré-formado e apresentaram tamanho de partícula nanométrico, índice de polidispersão adequado, com potencial zeta positivo para as nanocápsulas revestidas e negativo para as não revestidas. O teor de tioconazol foi 1,00 mg/mL e o pH das formulações levemente ácido. Ambas possibilitaram o controle da liberação do fármaco e apresentaram atividade antifúngica. A formulação ungueal apresentou características adequadas à aplicação ungueal preservando as nanoestruturas, e maior percentual de recuperação de tioconazol no estudo de penetração ungueal. A análise por microscopia confocal demonstrou uma penetração de mais de 30% da espessura ungueal a partir das formulações nanoestruturadas. Em modelo ex vivo de onicomicose, as formulações ungueais demonstraram-se equivalentes à formulação comercial com uma concentração de tioconazol 280 vezes menor. Ainda, a inclusão do tioconazol nas nanocápsulas reduziu o potencial irritante in vitro do fármaco.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeSilva, Cristiane de Bona dahttp://lattes.cnpq.br/6029111646602279Guterres, Sílvia Stanisçuaskihttp://lattes.cnpq.br/4662273973783290Senna, Elenara Maria Teixeira Lemoshttp://lattes.cnpq.br/7306169864153373Cruz, Letíciahttp://lattes.cnpq.br/3095970241017527Canto, Gizele Scotti dohttp://lattes.cnpq.br/2076175621657265Flores, Fernanda Cramer2021-01-23T11:36:07Z2021-01-23T11:36:07Z2016-02-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20270porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2021-01-24T06:02:34Zoai:repositorio.ufsm.br:1/20270Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-01-24T06:02:34Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais Innovative nanotechnological formulations for topical treatment of superficial mycosis |
title |
Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais |
spellingShingle |
Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais Flores, Fernanda Cramer Tioconazol Nanopartículas lipídicas Nanocápsulas poliméricas Matérias-primas vegetais Micoses superficiais Penetração cutânea Onicomicoses Penetração ungueal Tioconazole Lipid nanocparticles Polymeric nanocapsules Natural raw materials Superficial mycosis Skin penetration Onychomycosis Nail penetration CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais |
title_full |
Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais |
title_fullStr |
Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais |
title_full_unstemmed |
Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais |
title_sort |
Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais |
author |
Flores, Fernanda Cramer |
author_facet |
Flores, Fernanda Cramer |
author_role |
author |
dc.contributor.none.fl_str_mv |
Silva, Cristiane de Bona da http://lattes.cnpq.br/6029111646602279 Guterres, Sílvia Stanisçuaski http://lattes.cnpq.br/4662273973783290 Senna, Elenara Maria Teixeira Lemos http://lattes.cnpq.br/7306169864153373 Cruz, Letícia http://lattes.cnpq.br/3095970241017527 Canto, Gizele Scotti do http://lattes.cnpq.br/2076175621657265 |
dc.contributor.author.fl_str_mv |
Flores, Fernanda Cramer |
dc.subject.por.fl_str_mv |
Tioconazol Nanopartículas lipídicas Nanocápsulas poliméricas Matérias-primas vegetais Micoses superficiais Penetração cutânea Onicomicoses Penetração ungueal Tioconazole Lipid nanocparticles Polymeric nanocapsules Natural raw materials Superficial mycosis Skin penetration Onychomycosis Nail penetration CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Tioconazol Nanopartículas lipídicas Nanocápsulas poliméricas Matérias-primas vegetais Micoses superficiais Penetração cutânea Onicomicoses Penetração ungueal Tioconazole Lipid nanocparticles Polymeric nanocapsules Natural raw materials Superficial mycosis Skin penetration Onychomycosis Nail penetration CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Superficial mycoses are fungal diseases caused on skin, hair and nails and are among the infectious diseases with the highest incidence and difficult to treat, making them a serious public health problem. The purpose of this study was the development of nanotechnological based formulations, contemplating the use of vegetable lipids for topical application of tioconazole, aiming the treatment of superficial mycoses.The first part of this work was focused on the development of hydrogels containing Mangospheres (lipid nanoparticles prepared with mango butter, meleuca oil and tioconazole at 2 mg/mL), and hydrogels containing tioconazoleloaded copaiba oil polymeric nanocapsules, coated and uncoated with chitosan (1 mg/mL). Mangospheres were prepared by high-pressure homogenization technique and the polymeric nanocapsules by interfacial deposition of pre-formed polymer method. The nanoparticles showed adequate physicochemical characteristics. The mean particle size was around 100 nm for Mangospheres and 170 nm for copaiba oil nanocapsules. The formulations showed the polydispersity index below 0.15, slightly acid pH and negative zeta potential for Mangospheres and uncoated nanocapsules and positive for chitosan-coated nanocapasules. Tioconazole content was 1.64-1.74 mg/mL for Mangospheres and 1.00 mg/mL for copaiba nanocapsules. The formulations presented antifungal activity and a great control of tioconazole release was observed for Mangospheres containing melaleuca oil and for the uncoated nanocapsules. The nanostructures were preserved after incorporation into hydrogels. The hydrogels showed slightly acidic pH, drug content close to the theoretical values and flow characteristics in accordance with Casson model for hydrogels containing Mangopheres. The hydrogels containing the cationiccoated polymeric nanocapsules presented Hershel-Bulkley flow model and bioadhesivity. In vitro skin permeation studies showed tioconazole targeting to stratum corneum for the hydrogels presenting Mangospheres and copaiba oil nanocapsules, with greater retention for the hydrogels containing the coated copaiba oil nanocapsules. The second part of the present work focused on studies related to the optimization of formulations for the treatment of onychomycosis, starting with a review of the literature on the use of essential oils in treating these infections. In addition, it was aimed to develop a nail formulation containing tioconazole associated with nanocapsules of medium chain triglycerides coated with chitosan. The coated and uncoated nanocapsules were obtained by interfacial deposition of pre-formed polymer and showed nanometric size, adequate polydispersity index and positive zeta potential for the coated nanocapsules and negative for the uncoated particles. Tioconazole content was 1.00 mg/mL and pH with slightly acid values. Both formulations showed control of tioconazole release and antifungal activity. The nail formulation showed adequate characteristics for nail application and preserved the nanostructures while on nail permeation studies, presented higher percentage of tioconazole recovery from nail plate. Confocal microscopy analysis showed more than 30% of nail thickness in penetration depth of the fluorescent marker form the formulations. In an ex vivo onychomycosis model, the ungual formulations showed equivalent activity compared to the commercial tioconazole formulation with tioconazole concentration of 280 times lower. In addition, the association of tioconazole to polymeric nanocapsules led to a reduction of the irritative potential of the drug in vitro. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-02-19 2021-01-23T11:36:07Z 2021-01-23T11:36:07Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/20270 |
url |
http://repositorio.ufsm.br/handle/1/20270 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805922023945273344 |