Desarrollo de un sistema de liberación basado en nanopartículas de quitosano para la optimización del uso terapeútico de interferón alfa

Interferon alpha (IFN?) is protein approved for the treatment of viral and oncological\npathologies, which must be administered parenterally. Our aim was to develop a delivery\nsystem for IFN?-2b by means of a simple, reproducible and economical methodology that\nwould enable its oral administration...

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Autor principal: Cánepa, Camila Belén
Otros Autores: Sosnik, Alejandro
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Facultad de Farmacia y Bioquímica 2018
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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_2932
http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2932.dir/2932.PDF
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Sumario:Interferon alpha (IFN?) is protein approved for the treatment of viral and oncological\npathologies, which must be administered parenterally. Our aim was to develop a delivery\nsystem for IFN?-2b by means of a simple, reproducible and economical methodology that\nwould enable its oral administration. Spherical chitosan nanoparticles (CTNPs) of 47 nm were\nobtained by ionotropic gelation. These were stable at pH 5.0-7.0 and mucoadhesive. In\naddition, CTNPs were safe and showed a moderate permeability through colonic cells in vitro.\nThe encapsulation efficiency of the drug loaded system (CT-IFNNPs) was 98%; the\nphysicochemical characteristics were not altered with respect to the unloaded CTNPs. In vitro\nantiviral activity of the CT-IFNNPs was analogous to that of the commercial IFN?. After oral\nadministration of CT-IFNNPs (0,3MIU) to Balb/C mice, IFN? was detected in plasma.\nFurthermore, 3 daily doses of CT-IFNNPs induced the production of pro-inflammatory\ncytokines in spleen, to a greater extent than the pristine IFN? administered subcutaneously,\nsuggesting biological functionality of the drug. Thus, we report for the first time the\ndevelopment of a formulation that enabled the absorption of orally administered IFN?,\nelucidating a new avenue for non-invasive and eventually safer administration routes for\nhighly labile biological drugs, compared to conventional parenteral therapy.