DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER
Ano de defesa: | 2012 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Franciscana
|
Programa de Pós-Graduação: |
Mestrado Acadêmico em Nanociências
|
Departamento: |
Biociências e Nanomateriais
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/203 http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/324 |
Resumo: | The hypothesis of Alzheimer s Disease (DA) may be related to high serum cholesterol levels made lipid-lowering drugs, as lovastatin (LV) and simvastatin (SV), potential choices of treatment against this disease. However, low levels of simvastatin and lovastatin are able to cross the blood brain barrier (BHE) and side effects associated to these drugs are a problem for their use in diseases affecting the central nervous system (SNC). Therefore, considering the therapeutic potentials of nanocapsules, the aim of this work was develop, characterize and evaluate the biological effect of NC containing SV or LV in animal models of DA induced by hypercholesterolemia. NC polymeric suspensions were prepared with SV (NCSV) or LV (NCLV) by interfacial deposition of preformed polymers. NCLV and NCSV exhibited average particle size of 204.0 ± 1.5 nm and 205.5 ± 0.5 nm, respectively, as monodispersed systems, with slightly acid pH (around 6) and negative zata potential (-23.29 ± 0.80 for NCLV and -19.5 ± 0.13 mV for NCSV). The analysis by fourier transform infrared spectroscopy and differential canning calorimetry (DSC) indicated that no chemical reactions occurred among components during nanocapsule preparation. The DSC analysis showed that sorbitan monostearate was dissolved in the oil core. The X-ray diffractometry, scanning electron microscopy (SEM), optical microscopy and drug content showed that a large amount lovastatine was presented in a crystalline form in NCLV, and they were not encapsulated. On the other hand, for NCSV, simvastatin was amorphous, indicating absent of drug crystals and that the drug was molecularly dispersed in NC. The encapsulation efficacy of LV was low (21.52 ± 1.4 %) while of SV was very high (99.18 ± 0.7 %). The animals fed with hyperlipemic diet showed significantly increase of serum cholesterol levels and LDL-cholesterol, however the treatment with unencapsulated SV and nanocapsules loading SV 1 mg/kg/dia and 3 mg/kg/day, during 45 days, not sufficient for reducing these biochemistry parameters. The serum triglycerides and VLDL-cholesterol levels did not show significant variations. The HDL-cholesterol was higher for animals treated with free SV (3mg/kg/day). The animals fed with hyperlipemic diet and/or treated with free drug or loaded in nanocapsules didi not show any increase of liver transaminases, indicating that there was no liver damage. The activity of pyruvate kinase and creatine kinase suggested that there were not any changes in neuronal energy metabolism. The hypercholesterolemia was capable of inducing alterations in cognition in Wistar rats. The NCSV showed promising effects in DA, once the animals were able to enhance memory when subjected to passive avoidance test. Free SV led to no significant alterations in learning and memory. The histology results suggested the presence of some brain lesions in some groups, indicating a possible neurodegeneration. Based on these results, we can conclude that simvastatin nanocapsules are a promising alternative in the treatment of cognitive loss due to high cholesterol levels and deserves more studies. |
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Raffin, Renata PlatcheckCPF:76201643087http://lattes.cnpq.br/9315943331569148CPF:00760261083http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4162307E9Lorenzoni, Ricardo2018-06-27T18:56:25Z2012-04-23LORENZONI, Ricardo. DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER. 2012. 118 f. Dissertação (Mestrado em Biociências e Nanomateriais) - Universidade Franciscana, Santa Maria, 2012.http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/203http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/324The hypothesis of Alzheimer s Disease (DA) may be related to high serum cholesterol levels made lipid-lowering drugs, as lovastatin (LV) and simvastatin (SV), potential choices of treatment against this disease. However, low levels of simvastatin and lovastatin are able to cross the blood brain barrier (BHE) and side effects associated to these drugs are a problem for their use in diseases affecting the central nervous system (SNC). Therefore, considering the therapeutic potentials of nanocapsules, the aim of this work was develop, characterize and evaluate the biological effect of NC containing SV or LV in animal models of DA induced by hypercholesterolemia. NC polymeric suspensions were prepared with SV (NCSV) or LV (NCLV) by interfacial deposition of preformed polymers. NCLV and NCSV exhibited average particle size of 204.0 ± 1.5 nm and 205.5 ± 0.5 nm, respectively, as monodispersed systems, with slightly acid pH (around 6) and negative zata potential (-23.29 ± 0.80 for NCLV and -19.5 ± 0.13 mV for NCSV). The analysis by fourier transform infrared spectroscopy and differential canning calorimetry (DSC) indicated that no chemical reactions occurred among components during nanocapsule preparation. The DSC analysis showed that sorbitan monostearate was dissolved in the oil core. The X-ray diffractometry, scanning electron microscopy (SEM), optical microscopy and drug content showed that a large amount lovastatine was presented in a crystalline form in NCLV, and they were not encapsulated. On the other hand, for NCSV, simvastatin was amorphous, indicating absent of drug crystals and that the drug was molecularly dispersed in NC. The encapsulation efficacy of LV was low (21.52 ± 1.4 %) while of SV was very high (99.18 ± 0.7 %). The animals fed with hyperlipemic diet showed significantly increase of serum cholesterol levels and LDL-cholesterol, however the treatment with unencapsulated SV and nanocapsules loading SV 1 mg/kg/dia and 3 mg/kg/day, during 45 days, not sufficient for reducing these biochemistry parameters. The serum triglycerides and VLDL-cholesterol levels did not show significant variations. The HDL-cholesterol was higher for animals treated with free SV (3mg/kg/day). The animals fed with hyperlipemic diet and/or treated with free drug or loaded in nanocapsules didi not show any increase of liver transaminases, indicating that there was no liver damage. The activity of pyruvate kinase and creatine kinase suggested that there were not any changes in neuronal energy metabolism. The hypercholesterolemia was capable of inducing alterations in cognition in Wistar rats. The NCSV showed promising effects in DA, once the animals were able to enhance memory when subjected to passive avoidance test. Free SV led to no significant alterations in learning and memory. The histology results suggested the presence of some brain lesions in some groups, indicating a possible neurodegeneration. Based on these results, we can conclude that simvastatin nanocapsules are a promising alternative in the treatment of cognitive loss due to high cholesterol levels and deserves more studies.A hipótese de que o desenvolvimento da Doença de Alzheimer (DA) pode estar relacionado com altos níveis de colesterol plasmático faz dos fármacos hipolipemiantes, como Lovastatina (LV) e Sinvastatina (SV), potenciais terapêuticos frente a esta enfermidade. Contudo, a baixa penetração da LV e da SV através da barreira hematoencefálica (BHE) e os efeitos colaterais que elas podem ocasionar apresentam-se como um impasse para a utilização destes fármacos frente a doenças que acometem o sistema nervoso central. Deste modo, considerando as potencialidades terapêuticas que as nanocápsulas poliméricas (NC) podem promover, este trabalho teve como objetivo, desenvolver, caracterizar e avaliar o efeito biológico de NC contendo SV ou LV frente ao modelo animal da DA induzida por hipercolesterolemia. Assim, foram desenvolvidas suspensões de NC poliméricas contendo SV (NCSV) ou LV (NCLV) através do método de deposição interfacial do polímero pré-formado. As suspensões exibiram tamanho médio de partícula homogêneo (204,0 ± 1,5 nm para as NCLV e 205,5 ± 0,5 nm para as NCSV), com baixo índice de polidispersão, caracterizando sistema monodispersos, com pH levemente ácido (em torno de 6) e potencial zeta negativo (-23,29 ± 0,80 mV para as NCLV e -19,5 ± 0,13 mV para as NCSV). As análises de espectroscopia na região do infravermelho com transformada de Fourier e calorimetria exploratória diferencial (DSC) indicaram que não houve reação química entre os componentes da formulação durante a produção das formulações. A avaliação por DSC mostrou que o monoestearato de sorbitano encontra-se dissolvido no núcleo oleoso das partículas. A difração de raios-X, a microscopia eletrônica de varredura (MEV), microscopia óptica revelaram que grande quantidade de fármaco apresentou-se sob a forma cristalina nas suspensões de NCLV. Por outro lado, a difração de raios-X, MEV e microscopia óptica revelaram que a SV encontra-se molecularmente dispersa nas suspensões de NCSV. Assim, a eficiência de encapsulação da LV foi baixa (21,52 ± 1,4 %) enquanto que para a SV foi alta (99,18 ± 0,7 %). Os animais alimentados com dieta hiperlipídica apresentaram aumento significativo do colesterol total e do LDL-colesterol, porém os tratamentos com SV livre e nanoencapsulada nas doses de 1 mg/kg/dia e 3 mg/kg/dia, durante 45 dias, não foram suficientes para reduzir estes parâmetros bioquímicos. Os triglicerídeos séricos e VLDL-colesterol não apresentaram variações significativas induzidas pela dieta ou como consequência do tratamento medicamentoso. O HDL-colesterol apresentou-se mais elevado apenas para os animais tratados com SV livre. Não houveram evidências de aumento das aminotransferases séricas, sugerindo ausência de dano hepático. As atividades da piruvatoquinase e da creatinoquinase indicaram que não houve alteração no metabolismo energético neuronal. A hipercolesterolemia foi capaz de induzir alterações cognitivas em ratos. A SV nanoencapsulada apresentou efeitos promissores frente à cognição, pois foram capazes de melhorar a memória dos animais submetidos ao teste de esquiva passiva. A SV livre não provocou alterações significativas no aprendizado e na memória dos animais neste teste. Os resultados histopatológicos indicam que houveram lesões cerebrais em alguns grupos de animais, indicando um possível efeito de neurodegeneração. Com base nos resultados, podemos concluir que as nanocápsulas de sinvastina são uma alternativa de uso terapêutico promissora e que merece mais estudos nos casos de perdas cognitivas por excesso de colesterol plasmático.Made available in DSpace on 2018-06-27T18:56:25Z (GMT). No. of bitstreams: 2 Ricardo Lorenzoni.pdf: 2169381 bytes, checksum: 9b086c1fe18c612a1d43ebe5f91c0f8f (MD5) Ricardo Lorenzoni.pdf.jpg: 3465 bytes, checksum: 60fb1578356f3148589233475ed9e01a (MD5) Previous issue date: 2012-04-23Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfhttp://tede.universidadefranciscana.edu.br:8080/retrieve/423/Ricardo%20Lorenzoni.pdf.jpgporUniversidade FranciscanaMestrado Acadêmico em NanociênciasUFNBRBiociências e Nanomateriaisestatinas, nanocápsulasDoença de Alzheimerbarreira hematoencefálicastatinsnanocapsulesAlzheimer s Diseaseblood brain barrierCNPQ::ENGENHARIASDESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMERinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional Universidade Franciscanainstname:Universidade Franciscana (UFN)instacron:UFNORIGINALRicardo Lorenzoni.pdfapplication/pdf2169381http://tede.universidadefranciscana.edu.br:8080/bitstream/UFN-BDTD/324/1/Ricardo+Lorenzoni.pdf9b086c1fe18c612a1d43ebe5f91c0f8fMD51THUMBNAILRicardo Lorenzoni.pdf.jpgimage/jpeg3465http://tede.universidadefranciscana.edu.br:8080/bitstream/UFN-BDTD/324/2/Ricardo+Lorenzoni.pdf.jpg60fb1578356f3148589233475ed9e01aMD52UFN-BDTD/3242018-06-27 15:56:25.092oai:tede.universidadefranciscana.edu.br:UFN-BDTD/324Repositório de Publicaçõeshttp://www.tede.universidadefranciscana.edu.br:8080/http://www.tede.universidadefranciscana.edu.br:8080/oai/requestopendoar:2018-06-27T18:56:25Repositório Institucional Universidade Franciscana - Universidade Franciscana (UFN)false |
dc.title.por.fl_str_mv |
DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER |
title |
DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER |
spellingShingle |
DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER Lorenzoni, Ricardo estatinas, nanocápsulas Doença de Alzheimer barreira hematoencefálica statins nanocapsules Alzheimer s Disease blood brain barrier CNPQ::ENGENHARIAS |
title_short |
DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER |
title_full |
DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER |
title_fullStr |
DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER |
title_full_unstemmed |
DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER |
title_sort |
DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER |
author |
Lorenzoni, Ricardo |
author_facet |
Lorenzoni, Ricardo |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Raffin, Renata Platcheck |
dc.contributor.advisor1ID.fl_str_mv |
CPF:76201643087 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9315943331569148 |
dc.contributor.authorID.fl_str_mv |
CPF:00760261083 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4162307E9 |
dc.contributor.author.fl_str_mv |
Lorenzoni, Ricardo |
contributor_str_mv |
Raffin, Renata Platcheck |
dc.subject.por.fl_str_mv |
estatinas, nanocápsulas Doença de Alzheimer barreira hematoencefálica |
topic |
estatinas, nanocápsulas Doença de Alzheimer barreira hematoencefálica statins nanocapsules Alzheimer s Disease blood brain barrier CNPQ::ENGENHARIAS |
dc.subject.eng.fl_str_mv |
statins nanocapsules Alzheimer s Disease blood brain barrier |
dc.subject.cnpq.fl_str_mv |
CNPQ::ENGENHARIAS |
description |
The hypothesis of Alzheimer s Disease (DA) may be related to high serum cholesterol levels made lipid-lowering drugs, as lovastatin (LV) and simvastatin (SV), potential choices of treatment against this disease. However, low levels of simvastatin and lovastatin are able to cross the blood brain barrier (BHE) and side effects associated to these drugs are a problem for their use in diseases affecting the central nervous system (SNC). Therefore, considering the therapeutic potentials of nanocapsules, the aim of this work was develop, characterize and evaluate the biological effect of NC containing SV or LV in animal models of DA induced by hypercholesterolemia. NC polymeric suspensions were prepared with SV (NCSV) or LV (NCLV) by interfacial deposition of preformed polymers. NCLV and NCSV exhibited average particle size of 204.0 ± 1.5 nm and 205.5 ± 0.5 nm, respectively, as monodispersed systems, with slightly acid pH (around 6) and negative zata potential (-23.29 ± 0.80 for NCLV and -19.5 ± 0.13 mV for NCSV). The analysis by fourier transform infrared spectroscopy and differential canning calorimetry (DSC) indicated that no chemical reactions occurred among components during nanocapsule preparation. The DSC analysis showed that sorbitan monostearate was dissolved in the oil core. The X-ray diffractometry, scanning electron microscopy (SEM), optical microscopy and drug content showed that a large amount lovastatine was presented in a crystalline form in NCLV, and they were not encapsulated. On the other hand, for NCSV, simvastatin was amorphous, indicating absent of drug crystals and that the drug was molecularly dispersed in NC. The encapsulation efficacy of LV was low (21.52 ± 1.4 %) while of SV was very high (99.18 ± 0.7 %). The animals fed with hyperlipemic diet showed significantly increase of serum cholesterol levels and LDL-cholesterol, however the treatment with unencapsulated SV and nanocapsules loading SV 1 mg/kg/dia and 3 mg/kg/day, during 45 days, not sufficient for reducing these biochemistry parameters. The serum triglycerides and VLDL-cholesterol levels did not show significant variations. The HDL-cholesterol was higher for animals treated with free SV (3mg/kg/day). The animals fed with hyperlipemic diet and/or treated with free drug or loaded in nanocapsules didi not show any increase of liver transaminases, indicating that there was no liver damage. The activity of pyruvate kinase and creatine kinase suggested that there were not any changes in neuronal energy metabolism. The hypercholesterolemia was capable of inducing alterations in cognition in Wistar rats. The NCSV showed promising effects in DA, once the animals were able to enhance memory when subjected to passive avoidance test. Free SV led to no significant alterations in learning and memory. The histology results suggested the presence of some brain lesions in some groups, indicating a possible neurodegeneration. Based on these results, we can conclude that simvastatin nanocapsules are a promising alternative in the treatment of cognitive loss due to high cholesterol levels and deserves more studies. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-04-23 |
dc.date.accessioned.fl_str_mv |
2018-06-27T18:56:25Z |
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info:eu-repo/semantics/publishedVersion |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
LORENZONI, Ricardo. DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER. 2012. 118 f. Dissertação (Mestrado em Biociências e Nanomateriais) - Universidade Franciscana, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/203 http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/324 |
identifier_str_mv |
LORENZONI, Ricardo. DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER. 2012. 118 f. Dissertação (Mestrado em Biociências e Nanomateriais) - Universidade Franciscana, Santa Maria, 2012. |
url |
http://tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/203 http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/324 |
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por |
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openAccess |
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Universidade Franciscana |
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Mestrado Acadêmico em Nanociências |
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