Interferonα Oral Administration: Development of a Nanotechnological Drug Delivery System Based on Polimeric Nanoparticles

CAMILA CANEPA; JULIETA IMPERIALE; CAROLINA BERINI; MIRNA BIGLIONE; ALEJANDRO SOSNIK

Ciudad Autónoma de Buenos Aires

Congreso; III International Congress in Translational Medicine; 2016

Interferon alpha (IFNa) is a protein drug used to treat oncological diseases and viral infections. Owing to its sensitivity to enzymatic degradation and limited absorption in the gastrointestinal tract, pegilated IFNa is administered via parenteral route once weekly which is associated with pain, allergic reactions and poor patient compliance. To overcome these problems, the design of a suitable drug delivery system (DDS) able to protect the drug in order to administer it orally would lead not only to greater acceptance and adherence to the treatment but also to a better quality of life for patients. In this context, we prepared IFNa2b loaded chitosan nanoparticles (IFN CS NPs) by ionotropic gelation method. Infrared spectra supported the formation of CS NPs. The amount of CS that formed NPs, colorimetrically determined, was 95.5%. Size, determined by dynamic light scattering (DLS), showed a bimodal distribution; the mean sizes were 381.7 ± 35.2 nm and 50.17± 6.96 for blank CS NPs, 353.0 ± 31.2 nm and 42.49 ± 23.75 for IFNa-loaded ones. The polidispersity index was 0.472 ± 0.030 and 0.407 ± 0.010, while the zeta potential (ZPot) 31.4 ± 4.6 mV and 31.8 ± 1.7 mV, respectively. The Z-Pot value suggests not only a net positive surface charge but also physical stability of the DDS as was confirmed at 4 and 25°C for 30 days by DLS results. The encapsulation efficiency was 99.5%. Transmission electron microscopy confirmed the size obtained by DLS results. The antiviral activity of encapsulated IFN determined in Vesicular Stomatitis Virus (VSV)infected MDBK cells, was comparable to commercial IFN. Preliminary pharmacokinetic studies in Balb/C mice showed absorption of IFNa2b after oral administration of IFN loaded CS NPs in opposition to different studies in which the drug was not detected in plasma following administration of free drug. These promising CS NPs show great potential for application in oral delivery of IFNa2b allowing an enhancement of patient compliance.