Estudio de sistemas nanométricos basados en lecitina como vehículos de oligonucleótidos en el tratamiento del cáncer de mama

The aim of the present Thesis was to study lecithin-based nanocarriers to be used as oligonucleotides delivery systems for breast cancer treatment. \nTwo kinds of carriers were developed, Phosphatidylcholine-based Nanoparticles (NPCs) and Mixed Nanoparticles (NMs). Their physicochemical properties w...

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Autor principal: Gándola, Yamila Belén
Otros Autores: Carlucci, Adriana
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2015
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Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_827
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_827.dir/827.PDF
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Sumario:The aim of the present Thesis was to study lecithin-based nanocarriers to be used as oligonucleotides delivery systems for breast cancer treatment. \nTwo kinds of carriers were developed, Phosphatidylcholine-based Nanoparticles (NPCs) and Mixed Nanoparticles (NMs). Their physicochemical properties were characterized in terms of particle size distribution, zeta potential, and morphology. Both formulations exhibited siRNA loading capacity. The NPCs showed no signs of cytotoxicity in a broad range of concentrations, and proved to be capable of mediating fluorescent siRNA delivery in MCF-7 human breast cancer cells, but no silencing effect was observed. NMs were also capable of mediating siRNA internalization and even showed efficient gene silencing in certain conditions. However, these formulations showed dose-dependent cytotoxicity related to composition and dose formulation.\nThe biological effects of these delivery systems were also studied. Cellular proliferation and signaling pathways activation were found to be dependent on both nanoparticles composition and physicochemical properties. This novel characterization of the nanocarriers biological activity, proved to be relevant even if their components are considered biocompatible.