Glutathione-loaded non-ionic surfactant niosomes: A new approach to improve oral bioavailability and hepatoprotective efficacy of glutathione

Abstract

A new formulation (niosomes) was prepared to enhance the bioavailability, hepatic tissue uptake, and hepatoprotective activity of glutathione (GSH). The GSH-loaded niosomes (nanoform, N-GSH) were formulated by the thin-film hydration technique using cholesterol/non-ionic surfactants (Span®40, Span®60, and Tween®80) at a componential ratio of 1:1 and 2:1. The hepatoprotective activity of N-GSH, GSH, and the standard silymarin against CCl4-induced liver damage and oxidative stress were tested on the rats' model. The hepatic morphology and histopathological characters were also investigated. The tissue contents of N-GSH were analysed using a concurrently validated RP-HPLC method. The optimized niosomes, composed of glutathione (500 mg), cholesterol, and Span®60-Tween®80 at a molar ratio of 2:1 of cholesterol/non-ionic surfactant, displaying a particle size of 688.5 ± 14.52 nm, a zeta potential of -26.47 ± 0.158 mV, and encapsulation efficiency (EE) of 66 ± 2.8% was selected for in vivo testing. The levels of MDA, NO, SOD, NF-κB, IL-1β, and Bcl-2 were measured. The results demonstrated that hepatic tissue damage was ameliorated using N-GSH as confirmed by the morphological and histopathological examination compared to the CCl4 and control groups. The N-GSH significantly (p < 0.05) decreased the elevated levels of hepatic enzymes, oxidative parameters, and inflammatory mediators, as compared to silymarin and GSH. Also, N-GSH significantly (p < 0.05) increased GSH hepatocyte concentrations as compared to the control groups. The present study demonstrated that N-GSH remarkably improved glutathione oral bioavailability and hepatic tissue uptake, thereby introducing a new glutathione formulation to protect hepatic tissue from injury and restore its GSH contents.