Oral Pharmacokinetics of a Chitosan-Based Nano- Drug Delivery System of Interferon Alpha

Abstract: Interferon alpha (IFN) is a protein drug used to treat viral infections and cancer diseases. Dueto its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability,which is associated with severe side eects. We hypothesized that the nanoencapsulation...

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Detalles Bibliográficos
Autores: Imperiale, Julieta Celeste, Schlachet, Inbar, Lewicki, Marianela, Sosnik, Alejandro Dario, Biglione, Mirna Marcela
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/122998
Acceso en línea:http://hdl.handle.net/11336/122998
Access Level:acceso abierto
Palabra clave:IFNΑ
IN VITRO INTESTINAL PERMEABILITY
ORAL PHARMACOKINETICS
ORAL PROTEIN DELIVERY
POLYMERIC NANOPARTICLES
https://purl.org/becyt/ford/2.10
https://purl.org/becyt/ford/2
Descripción
Sumario:Abstract: Interferon alpha (IFN) is a protein drug used to treat viral infections and cancer diseases. Dueto its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability,which is associated with severe side eects. We hypothesized that the nanoencapsulation ofIFN within nanoparticles of the mucoadhesive polysaccharide chitosan would improve theoral bioavailability of this drug. In this work, we produced IFN-loaded chitosan nanoparticlesby the ionotropic gelation method. Their hydrodynamic diameter, polydispersity index andconcentration were characterized by dynamic light scattering and nanoparticle tracking analysis.After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability ofunmodified and poly(ethylene glycol) (PEG)-modified (PEGylated) nanoparticles was measured inmonoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated thatthe nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the studyof the oral pharmacokinetics of nanoencapsulated IFN in BalbC mice revealed two maxima andarea-under-the-curve of 56.9 pg*h/mL.