Preperation and characterization of Ribavirin nanocarriers towards improving the Hepatitis C treatment

Abstract

The hepatitis C virus (HCV) is among the leading causes of chronic liver diseases worldwide. The current primary treatment for HCV includes the oral administration of ribavirin (RBV) and pegylated interferon alpha (pegasys). The treatment is associated with toxic side effects due to the high daily dosage of 1200 mg RBV and overall low success rate. RBV possess a high accumulation rate in erythrocytes (red blood cells), therefore this makes it difficult for RBV to reach the target cells (hepatocytes) in the liver. The aim of this project was to load RBV into a polymer as nanoparticles (NPs) and characterize their physicochemical properties. The in vitro drug release was performed to study the ability of the polymer to release the drug. Eudragit L 100 (Eud) and RBV were chosen as polymer and drug respectively. Polyvinyl alcohol (PVA) and poloxamer 407 (POLO) were selected as emulsifying agents. Nanoprecipitation technique was employed to formulate the NPs by varying the surfactant concentration and the type of organic solvent. NPs characteristics such as particle size, polydispersity index (PDI) and zeta potential (ZP) were carried out by Malvern Zetasizer. The effects of surfactant concentration and organic solvent on particle size and ZP were analysed and the two optimised NPs were chosen for further characterisation. The optimised NPs had a diameter ranging from 200-250 nm and ZP of greater than -30 mV. The morphological study of the optimised NPs was carried by scanning electron microscopy and the NPs were spherical. The Fourier transform infrared spectroscopy showed the major peaks of both drug and polymer. There was clear evidence that there is a high amount of drug entrapped within the polymer. The ultraviolet visible spectroscopy studies showed a high drug encapsulation efficiency of >70%. The drug release studies showed a rapid release within the first 6 hours. The NPs showed the sensitive pH characteristic in vitro drug release. The Eud-RBV NPs showed a high thermal stability than pure RBV. The in vivo cytotoxicity in Daphnia magma showed that NPs were not toxic. Therefore, the use of NPs as drug delivery system for RBV shows substantial characteristics; this promise a possibility to decrease the high daily intake of RBV thus minimizing its toxic side effects.