Improved hepatoprotective activity of Beta vulgaris L. leaf extract loaded self-nanoemulsifying drug delivery system (SNEDDS): in vitro and in vivo evaluation

Abstract

Objective Beta vulgaris L. (beetroot) is a vegetable plant rich in phytochemical compounds such as phenolic acids, carotenoids and flavonoids. The objective of the current study is the development and optimization of self-nanoemulsifying drug delivery systems (SNEDDSs) to enhance the hepatoprotective activity of beet leaf (BL) extract. Methods Total flavonoids content was estimated in the BL extract and its solubility was evaluated in various vehicles to select proper component combinations. Pseudo-ternary phase diagrams were constructed employing olive, linseed, castor and sesame oils (oil phase), Tween® 20 (Tw20) and Tween® 80 (Tw80) (surfactants (SAs)) as well as dimethyl sulfoxide (DMSO) and propylene glycol (PG) (co-surfactants (Co-SAs)). Optimization of formulations from the phase diagrams took place through testing their thermodynamic stability, dispersibility and robustness to dilution. Results Four optimized BL-SNEDDS formulations, comprising linseed oil or olive oil, Tw80 and DMSO at two SA/Co-SA ratios (2:1 or 3:1) were chosen. They exhibited high cloud point and percentage transmittance values with spherical morphology of mean droplet sizes ranging from 14.67 to 16.06 nm and monodisperse distribution with negatively charged zeta potential < −9.51 mV. The in vitro release profiles of the optimized formulations in pH 1.2 and 6.8 were nearly similar, with a non-Fickian release mechanism. In vivo evaluation of BL-SNEDDSs hepatoprotective activity in a thioacetamide-induced hepatotoxicity rat model depicted promoted liver functions, inflammatory markers and histopathological findings, most prominently in the group treated by F7. Conclusion The results indicate that SNEDDS, as a nanocarrier system, has potential to improve the hepatoprotective activity of the BL extract.