Sofosbuvir’s hepatoprotective efficacy in rats is enhanced by encapsulating in taurocholate-stabilized galactose-anchored bilosomes

Abstract

Background

In conjunction with other antiviral medicines, sofosbuvir (SOF) is an essential therapy for chronic hepatitis C. There is some debate over its influence on hepatic fibrosis. The use of nanotechnology in treatment has gained popularity, with the goal of delivering therapeutic substances to the liver to increase efficacy and decrease adverse effects. The aim of this study was to demonstrate the protective effect of sofosbuvir and the efficacy of incorporating nanoparticle galactosylated taurocholate bilosomal formula to SOF on thioacetamide-induced liver fibrosis.

Methods

Rats were divided into 7 groups: normal control, SOF, SOF encapsulated in galactosylated taurocholate bilosomal formula (nano-SOF), galactosylated taurocholate bilosomal formula (nanoparticle), thioacetamide (TAA), TAA-SOF and TAA-nano-SOF. Liver fibrosis was induced by TAA (200 mg/kg) intraperitoneal injection twice per week for 8 weeks. SOF, nanoparticle and nano-SOF were given (40 mg/Kg/day) orally from day one of the study. Serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and tissue transforming growth factor beta (TGF-β) were assessed. Also, histopathological assessment of hepatic tissue was done.

Results

Administration of SOF and TAA to normal rats resulted in significant increase in serum AST, ALT, ALP and tissue TGF-β₁ levels with variable degree of liver fibrosis. Additionally, rats in TAA group that received SOF therapy did not exhibit improved liver functions, TGF-β₁ level and liver fibrosis score. However, administering nano-sofosbuvir prophylactically to TAA-treated rats resulted in a considerable improvement in liver function tests, TGF-1 levels, with liver fibrosis score regression.

Conclusion

In contrast to free sofosbuvir, SOF encapsulated in galactosylated taurocholate bilosomal formula (nano-SOF) displayed hepatoprotective effects in rat with thioacetamide-induced hepatic fibrosis. These findings strongly support the concept that galactoylatedbilosomes are promising nanocarrier for the targeted delivery of sofosbuvir to the liver.