Desarrollo galénico de sistemas nanoparticulados innovadores para uso como vehículos de pequeños ARN de interferencia (siRNA)
Gene silencing by RNA interference (iRNA) is a specific mechanism that can be mediated by the delivery of chemically synthesized small interfering RNA (siRNA). The aim of the present work was to take advantage of phosphatidylcholine (PC) and bile salts? biocompatibility along with their physicochemi...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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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_1144 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_1144.dir/1144.PDF |
| Aporte de: |
| Sumario: | Gene silencing by RNA interference (iRNA) is a specific mechanism that can be mediated by the delivery of chemically synthesized small interfering RNA (siRNA). The aim of the present work was to take advantage of phosphatidylcholine (PC) and bile salts? biocompatibility along with their physicochemical properties for the development, optimization, characterization and in vitro evaluation of PC-based nanocarriers for siRNA delivery to MCF-7 human breast cancer cells and MDCK cells.\nLipoplexes formulated in different conditions were able to load siRNA and efficiently deliver it to the cells, without signs of cytotoxicity. Their physicochemical characterization exhibited particles of nanometric sizes and pH-dependant morphology, though with limited physical stability. Mixed systems composed of PC and bile salts were then optimized, obtaining low cytotoxic vehicles with high siRNA loading capacity and high transfection and silencing efficiency. Nanoparticles below 150 nm were observed and physicochemical evaluations accounted for small unilamellar vesicles or mixed micellar systems depending on each vehicle composition and formulation medium, making them suitable for in vivo further evaluation. Preliminary assays also suggest their promising use for plasmid DNA delivery.\n |
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