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

Julieta C Imperiale,Inbar Schlachet,Mirna M Biglione,Marianela Lewicki,Alejandro Sosnik

doi:10.3390/polym11111862

Abstract

Interferon alpha (IFNα) is a protein drug used to treat viral infections and cancer diseases. Due to its poor stability in the gastrointestinal tract, only parenteral administration ensures bioavailability, which is associated with severe side effects. We hypothesized that the nanoencapsulation of IFNα within nanoparticles of the mucoadhesive polysaccharide chitosan would improve the oral bioavailability of this drug. In this work, we produced IFNα-loaded chitosan nanoparticles by the ionotropic gelation method. Their hydrodynamic diameter, polydispersity index and concentration were characterized by dynamic light scattering and nanoparticle tracking analysis. After confirming their good cell compatibility in Caco-2 and WISH cells, the permeability of unmodified and poly(ethylene glycol) (PEG)-modified (PEGylated) nanoparticles was measured in monoculture (Caco-2) and co-culture (Caco-2/HT29-MTX) cell monolayers. Results indicated that the nanoparticles cross the intestinal epithelium mainly by the paracellular route. Finally, the study of the oral pharmacokinetics of nanoencapsulated IFNα in BalbC mice revealed two maxima and area-under-the-curve of 56.9 pg*h/mL.

Highlights

Biological drugs are increasingly positioned in the pharmaceutical market because their high affinity for the different therapeutic targets enhances treatment efficacy and lowers side-effects.their high molecular weight, low lipophilicity and polyelectrolyte nature preclude absorption by transmucosal routes that are more patient-compliant
Results showed that CT-NPs incubated at pH 1, their Dtheir h by half
These findings suggest that CT-NPs are unstable at pH 1

Summary

Introduction

Biological drugs are increasingly positioned in the pharmaceutical market because their high affinity for the different therapeutic targets enhances treatment efficacy and lowers side-effects. Their high molecular weight, low lipophilicity and polyelectrolyte nature preclude absorption by transmucosal routes that are more patient-compliant. Interferon alpha (IFNα) is a cytokine that exhibits a broad spectrum of antiviral, immunomodulatory, antiproliferative and antitumoral activities [2]. The antitumor and antiviral activity of IFNα stems from the activation of CD4 and CD8 T lymphocytes and natural killer cells, Polymers 2019, 11, 1862; doi:10.3390/polym11111862 www.mdpi.com/journal/polymers

Methods

Results

Conclusion