Enhanced prevention of progression of non alcoholic fatty liver to steatohepatitis by incorporating pumpkin seed oil in nanoemulsions

Abstract

Nanoemulsions (NEs) possess several advantages and have applications in controlled drug delivery and targeting. Pumpkin seed oil (PSO) oral NEs were dispensed with the objective of improving its oral bioavailability and prolonging its therapeutic efficacy. Phase diagrams were constructed. Eighteen formulations were selected from Labrafac™ PG phase diagrams. They passed thermodynamic stability tests and 10 out of them passed dispersibility tests in distilled water and 0.1N HCl. Four formulations were compatible with PSO and showed total phenolic content ranging from 5.71 to 6.51mg/kg of the incorporated PSO, expressed as gallic acid equivalent (GAE). The selected formulations revealed percolative electric conductivity, physiologically compatible pH, globule size <400nm, optimum polydispersity index (PDI), negatively charged zeta potential values, and were sterically stabilized by Tween 80. The morphology investigation revealed spherical shaped globules using transmission electron microscopy. PSO NE formulation (F7), comprised of PSO (10%), Labrafac™ PG (17%), Tween 80 (31.5%), PEG 400 (31.5%) and water (10%) revealed the highest percent cumulative total phenolic content released after 24h. F7 was evaluated for prevention of progression of fatty liver to steatohepatitis and fibrosis in a steatohepatitis and fibrosis induced rat model. Two oral doses (50 and 100mg/kg rat body weight) were investigated thrice weekly. Results showed improvement of the different plasma lipid profile parameters as well as malondialdehyde and tumor necrosis factor-α, as representative of lipid peroxidation and inflammation, respectively, along with reduction of liver fat and improvement of hepatic function on treatment with PSO NE (F7); the high dose was more promising. Thus, incorporating PSO in nanosized NE system (F7) holds a promising technological approach to enhance the inhibition of the progression of fatty liver to steatohepatitis.