DESENVOLVIMENTO, CARACTERIZAÇÃO E EFEITO BIOLÓGICO DE NANOCÁPSULAS POLIMÉRICAS CONTENDO ESTATINAS PARA O TRATAMENTO DA DOENÇA DE ALZHEIMER
| Ano de defesa: | 2012 |
|---|---|
| Autor(a) principal: |
Lorenzoni, Ricardo
 |
| Orientador(a): |
Raffin, Renata Platcheck
|
| 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. |