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

Abstract

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.