DESENVOLVIMENTO E CARACTERIZAÇÃO DE VESÍCULAS LIPOSSOMAIS CONTENDO TRIÓXIDO DE ARSÊNIO

• Ano de defesa: 2015
• Autor(a) principal: Moreira, Mauber Eduardo Schultz
• Orientador(a): Mortari, Sergio Roberto
• Banca de defesa: Fiocruz, Armando de Oliveira Schubach, Santos, Roberto Christ Vianna
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Centro Universitário Franciscano
• Programa de Pós-Graduação: Programa de Pós-Graduação em Nanociências
• Departamento: Biociências e Nanomateriais
• País: Brasil
• Palavras-chave em Português: Evaporação em fase reversa. Lipossomas. Trióxido de arsênio. Ultrassonicação
• Palavras-chave em Inglês: Arsenic trioxide. Liposome. Reverse phase evaporation. Ultrasonication
• Área do conhecimento CNPq: Biociências e Nanomateriais
• Link de acesso: http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/538

Cancer is a public health problem of great impact. Relapses require higher doses of drugs or new approaches to minimizing toxicity. The use of liposome-based carrier systems pharmaceuticals may be an alternative by the use of the enhanced permeability and retention effect present in the tumor area. The aim of this project was to develop and characterize liposomes containing arsenic trioxide (ATO). They were prepared according reverse phase evaporation method using ethyl acetate (EA) as solvent followed by ultrasonication with probe to reduce the size and homogenization. In determining the arsenic, titanium and residual EA we used Atomic Absorption Spectrometry with Graphite Furnace (GF- AAS), Mass Spectrometry Inductively Coupled Plasma (ICP -MS) and Gas Chromatography coupled to mass detector (GC-MS), respectively. We also carried out stability studies with formulations being subjected to room temperature (25° C), cooling (4 to 8° C) and climate chamber (40° C and 60% humidity) for a period of 90 days. Cytotoxicity assays were performed by the method of reduction of 3- (4,5) dimetiltialzoil 2,5 - diphenyltetrazolium bromide (MTT). Data of physical-chemical characterization showed that the best condition was sonication with a power of 750 W, 40% amplitude and cycles of 8 seconds on and 2 seconds off, to avoid overheating. The average particle size was 87.5±1.07 nm and polydispersity index (IPD) 0.28±0.03 for liposomes blank (BL) and 71.17±0.06 nm and 0.29±0.04 for liposomes containing TOA (LAs / LAS). TOA content of LAs was 1.0 mg ml-1 and the encapsulation efficiency (%EE) of 7,43±0.72%. ICP-MS showed the presence of titanium in the formulation and the determination of the residual solvent was below the tolerable limit. The stability study showed that formulations remained stable over a period of 30 days, regardless of storage condition wherein the stored under refrigeration remained stable for 60 days. Cytotoxicity assays with MTT revealed that in 72 hours the LB, AE and the buffer did not exercise death activity. The reverse phase evaporation method followed by ultrasonication appears to be suitable for obtaining liposomal vesicles containing arsenic trioxide .