Working Paper Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 22 September 2019 / Approved: 23 September 2019 / Online: 23 September 2019 (07:33:59 CEST)

How to cite: Imperiale, J.; Schlachet, I.; Marianela Lewicki, M.; Sosnik, A.; Biglione, M. Oral Pharmacokinetics of a Chitosan-Based Nano-Drug Delivery System of Interferon Alpha. Preprints 2019, 2019090263 Imperiale, J.; Schlachet, I.; Marianela Lewicki, M.; Sosnik, A.; Biglione, M. Oral Pharmacokinetics of a Chitosan-Based Nano-Drug Delivery System of Interferon Alpha. Preprints 2019, 2019090263

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 size, size distribution 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 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 oral pharmacokinetics in BalbC mice of nanoencapsulated IFNα revealed that it was absorbed reaching an area-under-the-curve of 56.9 pg.h/mL.

Subject Areas

ifnα; polymeric nanoparticles; oral protein delivery; in vitro intestinal permeability; oral pharmacokinetics

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