?rea de concentra??o: Ci?ncias farmac?uticas. / Data de aprova??o ausente. / Disponibiliza??o do conte?do parcial, conforme Termo de Autoriza??o no trabalho. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2016-12-20T19:20:11Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) sara_pacelli_sousa_marcial_parcial.pdf: 166236 bytes, checksum: c01c4f087337cd82c64b06b90a1cc4dc (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-01-17T18:55:36Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) sara_pacelli_sousa_marcial_parcial.pdf: 166236 bytes, checksum: c01c4f087337cd82c64b06b90a1cc4dc (MD5) / Made available in DSpace on 2017-01-17T18:55:36Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) sara_pacelli_sousa_marcial_parcial.pdf: 166236 bytes, checksum: c01c4f087337cd82c64b06b90a1cc4dc (MD5) Previous issue date: 2016 / Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG) / O paclitaxel (PTX) ? um agente quimioter?pico que tem uma importante fun??o no tratamento de v?rios tipos de c?ncer, especialmente o c?ncer de mama. No entanto, a baixa solubilidade do PTX em meio aquoso (coeficiente de parti??o log = 3,96) representa uma limita??o para a administra??o intravenosa. A formula??o convencional do PTX cont?m uma alta concentra??o de Cremofor-EL? (derivado polietoxilado do ?leo de r?cino), o qual induz significante toxicidade, restringindo sua utiliza??o cl?nica. A encapsula??o do PTX em sistema de libera??o de f?rmacos pode melhorar a absor??o e aumentar a sua efic?cia terap?utica. Neste estudo, tr?s diferentes nanossistemas lip?dicos contendo PTX, nanopart?culas lip?dicas s?lidas (NLS), nanoemuls?o (NE) e carreadores lip?dicos nanoestruturados (CLN) foram preparados e as propriedades f?sico-qu?micas e a atividade citotoxicidade in vitro foram avaliadas. Em rela??o ao di?metro m?dio, o CLN branco mostrou valor de di?metro aproximadamente 2 e 1,7 vezes menor que os obtidos para NLS e NE, respectivamente. A presen?a de PTX levou a um aumento significativo no di?metro das part?culas em todos os sistemas avaliados, exceto no NE. Al?m disso, o aumento da concentra??o do f?rmaco (0,01% para 0,025%) produziu um aumento do di?metro para a prepara??o de CLN. Todas as formula??es com PTX mostraram ?ndice de polidispers?o superior a 0,3, exceto para NE-PTX na concentra??o do f?rmaco igual a 0,01% (p/v). Valores negativos de potencial zeta foram observados para todas as formula??es avaliadas. CLN-PTX foi o sistema mais est?vel ap?s armazenado por 30 dias a 4 ?C. O estudo de citotoxicidade nas linhagens celulares de c?ncer de mama (MDA-MB-231 e MCF-7) demonstrou atividade citot?xica mais pronunciada para CLN-PTX do que para o PTX livre em ambos as linhagens celulares do tumor. Baseado nesses resultados, CLN-PTX parece ser uma ferramenta potencial para o tratamento do c?ncer de mama. / Disserta??o (Mestrado) ? Programa de P?s-gradua??o em Ci?ncias Farmac?uticas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, [2016]. / Paclitaxel (PTX) is a chemotherapeutic agent that plays an important role in the treatment of several types of human cancer, especially breast cancer. However, the low solubility of PTX in aqueous medium (partition coefficient log of 3.96) represents a barrier for intravenous administration. The conventional PTX formulation contains a high concentration of Cremophor-EL? (polyethoxylated castor oil), which is associated with significant toxicities restricting its clinical use. The encapsulation of the PTX in drug delivery systems could improve the uptake and increase its therapeutic efficacy. In this study, three different lipid nanosystems containing PTX, solid lipid nanoparticle (SLN), nanoemulsion (NE), and nanostructured lipid carrier (NLC) were prepared, and the physicochemical properties and in vitro cytotoxic activity were evaluated. Concerning the mean diameter, NLC blank showed diameter values approximately 2 and 1.7-fold lower than those obtained for SLN and NE, respectively. The presence of PTX leads to a significant increase in the particle diameter in all systems evaluated, except NE. In addition, increases in drug concentration (0.01% to 0.025%) produced an enhanced diameter for NLC preparation. All formulations containing PTX showed PI higher than 0.3, except for NE-PTX at drug concentration equal to 0.01% (w/v). Negative zeta potential values were observed in all formulations evaluated. NLC-PTX was the system more stable after storage for 30 days at 4 oC. The cytotoxicity studies on breast cancer cell lines (MDA-MB-231 and MCF-7) demonstrated cytotoxic activity more pronounced for NCL-PTX than for free PTX for both tumor cell lines. Thus, the results showed that NCL-PTX seems to be a potential tool for the treatment of breast cancer.