Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/19382 |
Resumo: | Epilepsy is a disease characterized by convulsive seizures, caused by an excessive neuronal electrical discharge, which affects 50 million people worldwide. Vinpocetine, derived from the alkaloid vincamine, is a neuroprotective that has antioxidant activity, being used in the treatment of neurodegenerative diseases. Researches have also shown an important antiepileptic activity for vinpocetine. However, this drug presents low solubility and short half-life, limiting its application in the pharmaceutical field. Thus, nanocapsules, which are also well researched for the cerebral delivery of drugs, become alternatives to deliver this active substance. In this work, vinpocetine-loaded poly(ɛ-caprolactone) (PCL) nanocapsule suspensions (0.5 mg/mL) were developed by the interfacial deposition of preformed polymer, containing medium chain triglycerides (NC-TCM-VP) or avocado oil (NC-ABA-VP) as core, in order to evaluate the physicochemical characteristics, drug release profile, both in vitro antioxidant and in vivo anticonvulsive activities of the drug associated with nanostructures. The nanocapsule suspensions had a size of 200 to 211 nm (Zetasizer®), PdI of 0.12 to 0.13, negative zeta potential, pH between 6.78 to 6.83, drug content close to 95% and encapsulation efficiency about 98 %. In the parameters evaluated, the type of oil influenced the viscosity of the formulations (capillary viscometer) and particle size distribution (Mastersizer®). Atomic force microscopy of the formulations demonstrated the presence of colloidal particles with shape close to spheres. Both developed systems were able to control the release of vinpocetine, compared to the free drug, by the dialysis bag diffusion technique using phosphate buffer pH 7.4: ethanol (70:30). The suspensions prepared with TCM presented better stability as well as a more homogeneous size distribution compared to avocado oil, and were then selected to follow the studies. The NC-TCM-VP formulations showed higher in vitro antioxidant activity than the free drug, by the TBARS method, as well as suspensions without drug. In the in vivo study, using animal model of seizure induced by pentylenetetrazole (PTZ), doses of 5 mg/kg or 10 mg/kg vinpocetine were evaluated, and treatments were performed 30 minutes or 4 h prior to administration of PTZ. The results demonstrated that NC-TCM-VP suspensions were able to improve the antiepileptic effect of the free drug or vehicle/nanocapsules without drug in some parameters evaluated, mainly in the shortest time (30 minutes). In view of the results obtained, nanocapsule suspensions are promising aqueous systems for the cerebral delivery of vinpocetine, a highly lipophilic drug, and may be a future alternative for the treatment of epilepsy. Vinpocetine is not yet used clinically for this purpose. |
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Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivanteNanocapsules of poly (ɛ-caprolactone) containing vinpocetine: development and evaluation of anticonvulsant activityNeuroprotetorPoli(ε-caprolactona)NanoestruturasLiberação cerebralAtividade anticonvulsivanteMicroscopia de força atômicaViscosidadeNeuroprotectorPoly(ε-caprolactone)NanostructuresBrain deliveryAnticonvulsive activityAtomic force microscopyViscosityCNPQ::CIENCIAS DA SAUDE::FARMACIAEpilepsy is a disease characterized by convulsive seizures, caused by an excessive neuronal electrical discharge, which affects 50 million people worldwide. Vinpocetine, derived from the alkaloid vincamine, is a neuroprotective that has antioxidant activity, being used in the treatment of neurodegenerative diseases. Researches have also shown an important antiepileptic activity for vinpocetine. However, this drug presents low solubility and short half-life, limiting its application in the pharmaceutical field. Thus, nanocapsules, which are also well researched for the cerebral delivery of drugs, become alternatives to deliver this active substance. In this work, vinpocetine-loaded poly(ɛ-caprolactone) (PCL) nanocapsule suspensions (0.5 mg/mL) were developed by the interfacial deposition of preformed polymer, containing medium chain triglycerides (NC-TCM-VP) or avocado oil (NC-ABA-VP) as core, in order to evaluate the physicochemical characteristics, drug release profile, both in vitro antioxidant and in vivo anticonvulsive activities of the drug associated with nanostructures. The nanocapsule suspensions had a size of 200 to 211 nm (Zetasizer®), PdI of 0.12 to 0.13, negative zeta potential, pH between 6.78 to 6.83, drug content close to 95% and encapsulation efficiency about 98 %. In the parameters evaluated, the type of oil influenced the viscosity of the formulations (capillary viscometer) and particle size distribution (Mastersizer®). Atomic force microscopy of the formulations demonstrated the presence of colloidal particles with shape close to spheres. Both developed systems were able to control the release of vinpocetine, compared to the free drug, by the dialysis bag diffusion technique using phosphate buffer pH 7.4: ethanol (70:30). The suspensions prepared with TCM presented better stability as well as a more homogeneous size distribution compared to avocado oil, and were then selected to follow the studies. The NC-TCM-VP formulations showed higher in vitro antioxidant activity than the free drug, by the TBARS method, as well as suspensions without drug. In the in vivo study, using animal model of seizure induced by pentylenetetrazole (PTZ), doses of 5 mg/kg or 10 mg/kg vinpocetine were evaluated, and treatments were performed 30 minutes or 4 h prior to administration of PTZ. The results demonstrated that NC-TCM-VP suspensions were able to improve the antiepileptic effect of the free drug or vehicle/nanocapsules without drug in some parameters evaluated, mainly in the shortest time (30 minutes). In view of the results obtained, nanocapsule suspensions are promising aqueous systems for the cerebral delivery of vinpocetine, a highly lipophilic drug, and may be a future alternative for the treatment of epilepsy. Vinpocetine is not yet used clinically for this purpose.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA epilepsia é uma doença caracterizada por crises convulsivas, oriundas de uma descarga elétrica neuronal excessiva, que acomete 50 milhões de pessoas no mundo inteiro. A vimpocetina, derivada do alcaloide vincamina, é um neuroprotetor que possui atividade antioxidante, sendo utilizada no tratamento de doenças neurodegenerativas. Pesquisas têm demostrado também um importante efeito antiepilético. No entanto, este fármaco apresenta baixa solubilidade e curta meia-vida, limitando sua aplicação no campo farmacêutico. Dessa forma, nanocápsulas, as quais também são muito pesquisadas para a liberação cerebral de fármacos, tornam-se alternativas para veicular esta substância ativa. Neste trabalho, foram desenvolvidas suspensões de nanocápsulas de poli(ɛ-caprolactona) (PCL) pelo método de deposição interfacial de polímero pré-formado, contendo triglicerídeos de cadeia média (NC-TCM-VP) ou óleo de abacate (NC-ABA-VP) como núcleo, para veicular vimpocetina (0,5 mg/mL), a fim de avaliar as características físico-químicas, o perfil de liberação, a atividade antioxidante in vitro e atividade anticonvulsivante in vivo do fármaco associado às nanoestruturas. As suspensões de nanocápsulas apresentaram tamanho de 200 a 211 nm (Zetasizer®), PdI de 0,12 a 0,13, potencial zeta negativo, pH entre 6,78 a 6,83, teor próximo a 95% e eficiência de encapsulamento de, aproximadamente, 98%. Nos parâmetros avaliados, o tipo de óleo utilizado influenciou a viscosidade das formulações (viscosímetro capilar) e a distribuição de tamanho de partículas (Mastersizer®). Microscopia de força atômica das formulações demonstrou a presença de partículas coloidais de formato próximo a esferas. Ambos os sistemas desenvolvidos foram capazes de controlar a liberação da vimpocetina, em comparação ao fármaco livre, pela técnica de difusão em sacos de diálise, utilizando tampão fosfato pH 7,4: etanol (70:30). As suspensões preparadas com TCM apresentaram melhor estabilidade, bem como distribuição de tamanho mais homogênea, em comparação às de óleo de abacate, sendo, então, selecionadas para dar seguimento aos estudos. As formulações NC-TCM-VP apresentaram atividade antioxidante in vitro superior ao fármaco livre, pelo método TBARS, assim como as suspensões sem o fármaco. No estudo in vivo, utilizando modelo animal de convulsão induzida por pentilenotetrazol (PTZ), doses de vimpocetina de 5 mg/Kg ou 10 mg/Kg foram avaliadas, e os tratamentos foram realizados 30 minutos ou 4 h antes da administração de PTZ. Os resultados demostraram que as suspensões NC-TCM-VP foram capazes de melhorar o efeito anticonvulsivante do fármaco livre ou em relação ao veículo/nanocápsulas sem fármaco, em alguns parâmetros avaliados, principalmente no menor tempo (30 minutos). Diante dos resultados obtidos, as suspensões de nanocápsulas são sistemas aquosos promissores para a liberação cerebral da vimpocetina, fármaco altamente lipofílico, podendo constituir uma alternativa futura para o tratamento da epilepsia, o qual ainda não é usado clinicamente para este fim.Universidade Federal de Santa MariaBrasilDesenvolvimento e Avaliação de Produtos FarmacêuticosUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeSchaffazick, Scheila Rezendehttp://lattes.cnpq.br/3671495623581433Ourique, Aline Ferreirahttp://lattes.cnpq.br/7478810804464054Silva, Cristiane de Bona dahttp://lattes.cnpq.br/6029111646602279Rosa, Carolina Pires2020-01-15T16:28:11Z2020-01-15T16:28:11Z2017-02-13info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/19382porAttribution-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:UFSM2022-10-06T19:58:20Zoai:repositorio.ufsm.br:1/19382Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-10-06T19:58:20Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante Nanocapsules of poly (ɛ-caprolactone) containing vinpocetine: development and evaluation of anticonvulsant activity |
title |
Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante |
spellingShingle |
Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante Rosa, Carolina Pires Neuroprotetor Poli(ε-caprolactona) Nanoestruturas Liberação cerebral Atividade anticonvulsivante Microscopia de força atômica Viscosidade Neuroprotector Poly(ε-caprolactone) Nanostructures Brain delivery Anticonvulsive activity Atomic force microscopy Viscosity CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante |
title_full |
Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante |
title_fullStr |
Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante |
title_full_unstemmed |
Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante |
title_sort |
Nanocápsulas de poli(ɛ-caprolactona) contendo vimpocetina: desenvolvimento e avaliação da atividade anticonvulsivante |
author |
Rosa, Carolina Pires |
author_facet |
Rosa, Carolina Pires |
author_role |
author |
dc.contributor.none.fl_str_mv |
Schaffazick, Scheila Rezende http://lattes.cnpq.br/3671495623581433 Ourique, Aline Ferreira http://lattes.cnpq.br/7478810804464054 Silva, Cristiane de Bona da http://lattes.cnpq.br/6029111646602279 |
dc.contributor.author.fl_str_mv |
Rosa, Carolina Pires |
dc.subject.por.fl_str_mv |
Neuroprotetor Poli(ε-caprolactona) Nanoestruturas Liberação cerebral Atividade anticonvulsivante Microscopia de força atômica Viscosidade Neuroprotector Poly(ε-caprolactone) Nanostructures Brain delivery Anticonvulsive activity Atomic force microscopy Viscosity CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Neuroprotetor Poli(ε-caprolactona) Nanoestruturas Liberação cerebral Atividade anticonvulsivante Microscopia de força atômica Viscosidade Neuroprotector Poly(ε-caprolactone) Nanostructures Brain delivery Anticonvulsive activity Atomic force microscopy Viscosity CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Epilepsy is a disease characterized by convulsive seizures, caused by an excessive neuronal electrical discharge, which affects 50 million people worldwide. Vinpocetine, derived from the alkaloid vincamine, is a neuroprotective that has antioxidant activity, being used in the treatment of neurodegenerative diseases. Researches have also shown an important antiepileptic activity for vinpocetine. However, this drug presents low solubility and short half-life, limiting its application in the pharmaceutical field. Thus, nanocapsules, which are also well researched for the cerebral delivery of drugs, become alternatives to deliver this active substance. In this work, vinpocetine-loaded poly(ɛ-caprolactone) (PCL) nanocapsule suspensions (0.5 mg/mL) were developed by the interfacial deposition of preformed polymer, containing medium chain triglycerides (NC-TCM-VP) or avocado oil (NC-ABA-VP) as core, in order to evaluate the physicochemical characteristics, drug release profile, both in vitro antioxidant and in vivo anticonvulsive activities of the drug associated with nanostructures. The nanocapsule suspensions had a size of 200 to 211 nm (Zetasizer®), PdI of 0.12 to 0.13, negative zeta potential, pH between 6.78 to 6.83, drug content close to 95% and encapsulation efficiency about 98 %. In the parameters evaluated, the type of oil influenced the viscosity of the formulations (capillary viscometer) and particle size distribution (Mastersizer®). Atomic force microscopy of the formulations demonstrated the presence of colloidal particles with shape close to spheres. Both developed systems were able to control the release of vinpocetine, compared to the free drug, by the dialysis bag diffusion technique using phosphate buffer pH 7.4: ethanol (70:30). The suspensions prepared with TCM presented better stability as well as a more homogeneous size distribution compared to avocado oil, and were then selected to follow the studies. The NC-TCM-VP formulations showed higher in vitro antioxidant activity than the free drug, by the TBARS method, as well as suspensions without drug. In the in vivo study, using animal model of seizure induced by pentylenetetrazole (PTZ), doses of 5 mg/kg or 10 mg/kg vinpocetine were evaluated, and treatments were performed 30 minutes or 4 h prior to administration of PTZ. The results demonstrated that NC-TCM-VP suspensions were able to improve the antiepileptic effect of the free drug or vehicle/nanocapsules without drug in some parameters evaluated, mainly in the shortest time (30 minutes). In view of the results obtained, nanocapsule suspensions are promising aqueous systems for the cerebral delivery of vinpocetine, a highly lipophilic drug, and may be a future alternative for the treatment of epilepsy. Vinpocetine is not yet used clinically for this purpose. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-02-13 2020-01-15T16:28:11Z 2020-01-15T16:28:11Z |
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.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/19382 |
url |
http://repositorio.ufsm.br/handle/1/19382 |
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 Desenvolvimento e Avaliação de Produtos Farmacêuticos UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Desenvolvimento e Avaliação de Produtos Farmacêuticos 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 |
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1805922169902858240 |