Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha
Ano de defesa: | 2015 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Goiás
|
Programa de Pós-Graduação: |
Programa de Pós-graduação em Ciências Farmacêuticas (FF)
|
Departamento: |
Faculdade Farmácia - FF (RG)
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.bc.ufg.br/tede/handle/tede/8190 |
Resumo: | The voriconazole (VOR) is an antifungal from the thiazole class, which has a proven action against dermatophytes, main cause of onychomycosis. Topical treatment of pathologies located in the nail is highly desirable, since oral administration of antifungal agents have been shown ineffective. Thus, the goal is the work was the development of nanostructured lipid carriers (NLC) for nail topical administration of the VOR. To quantify VOR in the nail plate, an analytical method was developed and validated by high-performance liquid chromatography (HPLC) with detection in the UV-vis. CLNs were obtained with glyceryl behenate, Miglyol®, polysorbate 80, sorbitan trioleate surfactant, and a cationic cetilpiridíneo chloride (CPC) and different drug loading. Nanoparticles were characterized for medium size, PdI, zeta potential, encapsulation efficiency and recovery, morphology by scanning electron microscopy (SEM), and the stability. Hydration factor of the formulations and permeation enhancers was performed. Analysis of dry and hydrated hooves treated with NLC were achieved by SEM. Release and in vitro permeation studies were performed with unloaded drug (VOR-free) and VOR loaded NLC. The drug quantification method was linear in the concentration range from 0.4 to 40 mg / mL. The limit of quantitation was 400 ng/mL. Furthermore, the method was able to analyze the VOR without suffering interference from components of the nail and NLC. The NLC (n = 3) loaded with drug showed positive surface charge (around +25 mV) and average size of 230 nm. The NLC obtained had 1.75% of drug load, with encapsulation efficiency of 74.52 (+ 2.13)%. Hydration factor studies showed that the formulation with the highest amount of Miglyol was able to hydrate the nail more as well as the urea, which was the best promotor enhancer for nail hydration. NLC developed with and without addition of promoters were stable for a period of 150 days. In vitro release studies showed that the release VOR from the NLC occurs in a controlled manner from the lipid matrix. There was no significant difference in drug penetration when applied CLNs with and without promoter, for the VOR-Free. Although amounts of drug were found more deeply with the use of the CLN in the sample depletion assays, which can facilitate treatment of nail affected by onychomycosis. |
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Taveira, Stephânia Fleuryhttp://lattes.cnpq.br/0382450621383005Alonso, AntônioMarreto, Ricardo NevesTaveira, Stephânia Fleuryhttp://lattes.cnpq.br/4761308167552564Rocha, Kamilla Amaral David2018-02-28T16:16:32Z2015-08-18ROCHA, K. A. D. Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha. 2015. 88 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2015.http://repositorio.bc.ufg.br/tede/handle/tede/8190The voriconazole (VOR) is an antifungal from the thiazole class, which has a proven action against dermatophytes, main cause of onychomycosis. Topical treatment of pathologies located in the nail is highly desirable, since oral administration of antifungal agents have been shown ineffective. Thus, the goal is the work was the development of nanostructured lipid carriers (NLC) for nail topical administration of the VOR. To quantify VOR in the nail plate, an analytical method was developed and validated by high-performance liquid chromatography (HPLC) with detection in the UV-vis. CLNs were obtained with glyceryl behenate, Miglyol®, polysorbate 80, sorbitan trioleate surfactant, and a cationic cetilpiridíneo chloride (CPC) and different drug loading. Nanoparticles were characterized for medium size, PdI, zeta potential, encapsulation efficiency and recovery, morphology by scanning electron microscopy (SEM), and the stability. Hydration factor of the formulations and permeation enhancers was performed. Analysis of dry and hydrated hooves treated with NLC were achieved by SEM. Release and in vitro permeation studies were performed with unloaded drug (VOR-free) and VOR loaded NLC. The drug quantification method was linear in the concentration range from 0.4 to 40 mg / mL. The limit of quantitation was 400 ng/mL. Furthermore, the method was able to analyze the VOR without suffering interference from components of the nail and NLC. The NLC (n = 3) loaded with drug showed positive surface charge (around +25 mV) and average size of 230 nm. The NLC obtained had 1.75% of drug load, with encapsulation efficiency of 74.52 (+ 2.13)%. Hydration factor studies showed that the formulation with the highest amount of Miglyol was able to hydrate the nail more as well as the urea, which was the best promotor enhancer for nail hydration. NLC developed with and without addition of promoters were stable for a period of 150 days. In vitro release studies showed that the release VOR from the NLC occurs in a controlled manner from the lipid matrix. There was no significant difference in drug penetration when applied CLNs with and without promoter, for the VOR-Free. Although amounts of drug were found more deeply with the use of the CLN in the sample depletion assays, which can facilitate treatment of nail affected by onychomycosis.O voriconazol (VOR) é um antifúngico da classe tiazol, que possui ação comprovada contra os dermatófitos, principais causadores da onicomicose. O tratamento tópico localizado de patologias na unha é altamente desejado, visto que a administração oral de antifúngicos têm se demonstrado ineficiente. Desta forma, o objetivo deste trabalho consiste no desenvolvimento de carreadores lipídicos nanoestruturados (CLN) para administração tópica do VOR na unha. Para a quantificação do VOR na placa ungueal foi desenvolvido e validado um método analítico por cromatografia líquida de alta eficiência (CLAE) com detecção no UV-vis. Os CLN foram obtidos com behenato de glicerila, Miglyol®, polissorbato 80, trioleato de sorbitano e tensoativo catiônico cloreto de cetilpiridnío (CPC), com diferentes cargas do fármaco. As nanopartículas foram caracterizadas quanto ao tamanho, PdI, potencial zeta, eficiência de encapsulação e recuperação, morfologia por microscopia eletrônica de varredura (MEV), e a estabilidade das mesmas. Avaliação do fator de hidratação das formulações e de promotores de permeação foi realizada. Análises dos cascos secos e hidratados com os CLN foram feitas por MEV. Estudos de liberação e permeação passiva in vitro do VOR livre e encapsulado em CLN foram realizados. O método de quantificação do fármaco mostrou-se linear na faixa de concentração de 0,4 a 40 μg/mL. O limite de quantificação foi de 400 ng/mL. Ainda, o método foi capaz de analisar o VOR sem sofrer interferência dos componentes da unha e dos CLN. Os CLN (n=3) carregados com fármaco apresentaram carga superficial positiva (em torno de +25 mV) e tamanho médio de 230 nm. Obtiveram-se carreadores com 1,75% de carga de fármaco e com eficiência de encapsulação de 74,52 (+ 2,13) %. A avaliação do fator de hidratação mostrou que a formulação com maior quantidade de Miglyol® foi capaz de hidratar mais a unha, assim como o promotor que apresentou melhor resultado foi a uréia (10%). Os CLN desenvolvidos com e sem adição de promotores se mostraram estáveis por um período de 150 dias. Os estudos de liberação in vitro demonstraram que a liberação do VOR a partir dos CLN ocorre de forma controlada a partir da matriz lipídica. Não houve diferença significativa na penetração do fármaco quando aplicado os CLN com e sem promotor, em relação ao VOR-Livre. Embora, quantidades de fármacos foram encontradas mais profundamente com uso dos CLN em ensaios de esgotamento da amostra, o que pode favorecer o tratamento de unhas acometidas pela onicomicose.Submitted by Liliane Ferreira (ljuvencia30@gmail.com) on 2018-02-28T14:49:21Z No. of bitstreams: 2 Dissertação - Kamilla Amaral David Rocha - 2015.pdf: 3193387 bytes, checksum: 6cc146ed197535b6a21627e8ffa4891c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2018-02-28T16:16:32Z (GMT) No. of bitstreams: 2 Dissertação - Kamilla Amaral David Rocha - 2015.pdf: 3193387 bytes, checksum: 6cc146ed197535b6a21627e8ffa4891c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2018-02-28T16:16:32Z (GMT). No. of bitstreams: 2 Dissertação - Kamilla Amaral David Rocha - 2015.pdf: 3193387 bytes, checksum: 6cc146ed197535b6a21627e8ffa4891c (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2015-08-18Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Farmacêuticas (FF)UFGBrasilFaculdade Farmácia - FF (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessVoriconazolOnicomicoseCarreador lipídico nanoestrututradoVoriconazoleOnichomycosisNanostructured lipid carrierFARMACIA::ANALISE E CONTROLE E MEDICAMENTOSDesenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unhaDevelopment of formulations containing voriconazole encapsulated in lipid nanoparticles and chemical absorption promoters for topical nail applicationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis824936988196152412600600600600601028116152420937562160250746569323362075167498588264571reponame:Biblioteca Digital de Teses e Dissertações da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.eng.fl_str_mv |
Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha |
dc.title.alternative.eng.fl_str_mv |
Development of formulations containing voriconazole encapsulated in lipid nanoparticles and chemical absorption promoters for topical nail application |
title |
Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha |
spellingShingle |
Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha Rocha, Kamilla Amaral David Voriconazol Onicomicose Carreador lipídico nanoestrututrado Voriconazole Onichomycosis Nanostructured lipid carrier FARMACIA::ANALISE E CONTROLE E MEDICAMENTOS |
title_short |
Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha |
title_full |
Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha |
title_fullStr |
Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha |
title_full_unstemmed |
Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha |
title_sort |
Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha |
author |
Rocha, Kamilla Amaral David |
author_facet |
Rocha, Kamilla Amaral David |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Taveira, Stephânia Fleury |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0382450621383005 |
dc.contributor.referee1.fl_str_mv |
Alonso, Antônio |
dc.contributor.referee2.fl_str_mv |
Marreto, Ricardo Neves |
dc.contributor.referee3.fl_str_mv |
Taveira, Stephânia Fleury |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4761308167552564 |
dc.contributor.author.fl_str_mv |
Rocha, Kamilla Amaral David |
contributor_str_mv |
Taveira, Stephânia Fleury Alonso, Antônio Marreto, Ricardo Neves Taveira, Stephânia Fleury |
dc.subject.por.fl_str_mv |
Voriconazol Onicomicose Carreador lipídico nanoestrututrado |
topic |
Voriconazol Onicomicose Carreador lipídico nanoestrututrado Voriconazole Onichomycosis Nanostructured lipid carrier FARMACIA::ANALISE E CONTROLE E MEDICAMENTOS |
dc.subject.eng.fl_str_mv |
Voriconazole Onichomycosis Nanostructured lipid carrier |
dc.subject.cnpq.fl_str_mv |
FARMACIA::ANALISE E CONTROLE E MEDICAMENTOS |
description |
The voriconazole (VOR) is an antifungal from the thiazole class, which has a proven action against dermatophytes, main cause of onychomycosis. Topical treatment of pathologies located in the nail is highly desirable, since oral administration of antifungal agents have been shown ineffective. Thus, the goal is the work was the development of nanostructured lipid carriers (NLC) for nail topical administration of the VOR. To quantify VOR in the nail plate, an analytical method was developed and validated by high-performance liquid chromatography (HPLC) with detection in the UV-vis. CLNs were obtained with glyceryl behenate, Miglyol®, polysorbate 80, sorbitan trioleate surfactant, and a cationic cetilpiridíneo chloride (CPC) and different drug loading. Nanoparticles were characterized for medium size, PdI, zeta potential, encapsulation efficiency and recovery, morphology by scanning electron microscopy (SEM), and the stability. Hydration factor of the formulations and permeation enhancers was performed. Analysis of dry and hydrated hooves treated with NLC were achieved by SEM. Release and in vitro permeation studies were performed with unloaded drug (VOR-free) and VOR loaded NLC. The drug quantification method was linear in the concentration range from 0.4 to 40 mg / mL. The limit of quantitation was 400 ng/mL. Furthermore, the method was able to analyze the VOR without suffering interference from components of the nail and NLC. The NLC (n = 3) loaded with drug showed positive surface charge (around +25 mV) and average size of 230 nm. The NLC obtained had 1.75% of drug load, with encapsulation efficiency of 74.52 (+ 2.13)%. Hydration factor studies showed that the formulation with the highest amount of Miglyol was able to hydrate the nail more as well as the urea, which was the best promotor enhancer for nail hydration. NLC developed with and without addition of promoters were stable for a period of 150 days. In vitro release studies showed that the release VOR from the NLC occurs in a controlled manner from the lipid matrix. There was no significant difference in drug penetration when applied CLNs with and without promoter, for the VOR-Free. Although amounts of drug were found more deeply with the use of the CLN in the sample depletion assays, which can facilitate treatment of nail affected by onychomycosis. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-08-18 |
dc.date.accessioned.fl_str_mv |
2018-02-28T16:16:32Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ROCHA, K. A. D. Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha. 2015. 88 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2015. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/8190 |
identifier_str_mv |
ROCHA, K. A. D. Desenvolvimento de formulações contendo voriconazol encapsulado em nanopartículas lipídicas e promotores químicos de absorção para aplicação tópica na unha. 2015. 88 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2015. |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/8190 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
824936988196152412 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 |
dc.relation.department.fl_str_mv |
6010281161524209375 |
dc.relation.cnpq.fl_str_mv |
6216025074656932336 |
dc.relation.sponsorship.fl_str_mv |
2075167498588264571 |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
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 Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Ciências Farmacêuticas (FF) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade Farmácia - FF (RG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
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Universidade Federal de Goiás (UFG) |
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UFG |
institution |
UFG |
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Biblioteca Digital de Teses e Dissertações da UFG |
collection |
Biblioteca Digital de Teses e Dissertações da UFG |
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repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UFG - Universidade Federal de Goiás (UFG) |
repository.mail.fl_str_mv |
tesesdissertacoes.bc@ufg.br ||tesesdissertacoes.bc@ufg.br |
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