Investigation of novel HCV therapies: Boscia angustifalia & Boscia senegalensis extracts loaded on galactosylated chitosan nanoparticles synthesized by eco-friendly method for HCV treatment

Abstract

Hepatitis C virus (HCV) is a major causative agent of chronic liver diseases including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Treatment of HCV has evolved from early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C after receiving therapy with direct-acting antivirals (DAA) with a 0.5 % chance of the hepatitis C virus recurrence, similar to other chronic viral infections. So, retreatment options following treatment failure have become crucial issues. Hence, this study aims to investigate a new promising therapy for HCV. In the field of nanomedicine, chitosan nanoparticles are well-known delivery systems that are frequently used as polymeric carriers. Galactosylated chitosan nanoparticles have been widely applied in HCV treatment. In this study, we have modified galactosylation by an eco-friendly method using l-ascorbic instead of hazardous reagents and we have loaded it with newly tested two Boscia extracts each in three different concentrations. The synthesized chitosan nanoparticles showed two dispersion peaks, at 196 ± 29 nm and 1.33 ± 0.36 μm, with a zeta potential of +3.3 ± 0.4mV with high stability in a range of 40.7 mV. The percentage of encapsulation of Boscia angustifalia extract was found to be 46.58 ± 1.33 % and for Boscia senegalensis extract was 9.77 ± 0.33 %. The release of Boscia angustifalia extract from the nanoparticles was about 40 % in acidic media after 180 min and about 60 % in normal pH. However, the release of Boscia senegalensis extract was 20 % in acidic media and 56 % in normal media after 24 h. Testing of these two newly developed composites against HCV was carried out using an in vitro system for the production of hepatitis C virus (HCV) which was established by infection of human hepatoma cells. Evidence for persistent virus production was monitored by the ELISA technique using an anti-HCV-specific antibody. Results obtained showed that all samples had an anti-HCV activity that increased by increasing concentration, and Boscia angustifalia had remarkable anti-HCV activity compared to Boscia senegalensis.

Keywords: Boscia angustifalia & Boscia senegalensis extracts; Drug delivery; Galactosylated nano chitosan; HCV.