Development of a drug delivery system (DDS) based on polymeric nanoparticles: The possibility of an oral administration route for interferon alpha

GHERARDI, M ; A SOSNICK; BERINI, M; ACOSTA GB; JCIMPERIALE; CANEPA C; M LEWICKI; MM BIBLIONE

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC) LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI) XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE; 2017

LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC) LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI) XLVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE)

DEVELOPMENT OF A DRUG DELIVERY SYSTEM (DDS) BASED ON POLYMERIC NANOPARTICLES:THE POSSIBILITY OF AN ORAL ADMINISTRATION ROUTEFOR INTERFERON ALPHACAMILA CÁNEPA1, CAROLINA A. BERINI1, MAGDALENA GHERARDI1, MARIANELA LEWICKI2, GABRIELA B.ACOSTA3, ALEJANDRO SOSNIK4, MIRNA M. BIGLIONE1, JULIETA C. IMPERIALE3,(1) Institute of Biomedical Research on Retroviruses and AIDS (INBIRS), UBA-CONICET, Buenos Aires, Argentina (2)Instituto de Investigaciones en Microbiología y Parasitología Médica, CONICET, Buenos Aires, Argentina (3) Instituteof Pharmacological Research (ININFA), National Scientific and Technical Research Council, School of Pharmacy andBiochemistry, University of Buenos Aires, Buenos Aires, Argentina (4) Laboratory of Pharmaceutical NanomaterialsScience, Technion, Haifa, IsraelInterferon alpha (IFNa) is a protein drug used to treatoncological diseases and viral infections. Owing to itssensitivity to enzymatic degradation and limited absorptionin the gastrointestinal tract, pegilated IFNa is administeredvia parenteral route once weekly which is associated withpain, allergic reactions and poor patient compliance. To AWARDS 85overcome these problems, the design of a suitable drugdelivery system (DDS) able to protect the drug in order toadminister it orally would lead not only to greater acceptanceand adherence to the treatment but also to a better quality oflife for patients. In this context, we prepared IFNa2b loadedchitosan nanoparticles (IFN CS NPs) by ionotropic gelationmethod. Infrared spectra supported the formation of CSNPs. The amount of CS that formed NPs, colorimetricallydetermined, was 95.5%. Size, determined by dynamic lightscattering (DLS), showed a bimodal distribution; the meansizes were 381.7 ± 35.2 nm and 50.17± 6.96 for blank CSNPs, 353.0 ± 31.2 nm and 42.49 ± 23.75 for IFNa-loadedones. The polidispersity index was 0.472 ± 0.030 and 0.407± 0.010, while the zeta potential (Z-Pot) 31.4 ± 4.6 mV and31.8 ± 1.7 mV, respectively. The Z-Pot value suggests notonly a net positive surface charge but also physical stability ofthe DDS as was confirmed at 4 and 25°C for 30 days by DLSresults. The encapsulation efficiency was 99.5%. Transmissionelectron microscopy confirmed the size obtained by DLSresults. The antiviral activity of encapsulated IFN determinedin Vesicular Stomatitis Virus (VSV) infected MDBK cells, wascomparable to commercial IFN. Preliminary pharmacokineticstudies in Balb/C mice showed absorption of IFNa2b afteroral administration of IFN loaded CS NPs in opposition todifferent studies in which the drug was not detected in plasmafollowing administration of free drug. These promising CSNPs show great potential for application in oral delivery ofIFNa2b allowing an enhancement of patient compliance