PEGylated terpesomes of curcumin for prominent hepatoprotective activity: Fabrication, optimization, biochemical analysis and in vivo evaluation

Abstract

Drug induced Liver Injury (DILI) is a major problem that usually leads to dose reduction or even drug withdrawal, leading to therapeutic failures. The current study aimed to formulate curcumin (CCM) PEGylated terpesomes and demonstrate its efficacy against carbon tetrachloride (CCl₄)- induced liver damage and oxidative stress. A 2³ factorial design was employed and a selected formula (SPT), comprising 7.5, 0.25 and 0.5 ratios of Polyethylene glycol 400 (PEG): CCM, fenchone: PEG and phosphatidyl choline: PEG, respectively was obtained. SPT exhibited satisfactory values of percentage entrapment efficiency, vesicular size and zeta potential (84.3 ± 1.9 %, 236.7 ± 5.3 nm and 33.7 ± 0.7 mV, respectively). Transmission Electron Microscopy revealed the spherical morphology of SPT vesicles, with VS like that obtained via zeta sizer. Release of CCM from SPT exhibited a biphasic pattern and obeyed Higuchian diffusion. SPT was stable in the refrigerator for up to three months. The biochemical analysis study revealed the superior hepatoprotective effect of CCM SPT compared to its aqueous suspension against CCl₄-induced liver damage and oxidative stress. The decrease in Aspartate transaminase (AST) and Alanine transaminase (ALT) and the increase in Glutathione (GSH) were 76 and 68.1 % and 9-folds vs 19.7 and 9.8 % and 1.6-folds, for CCM SPT and CCM aqueous suspension, respectively. Thus, SPT is considered a promising safe and effective hepatoprotective formula against DILI.