SNEDDS delivery of black sticky rice extract: Hepatoprotective and antioxidant potential

Black sticky rice ( Oryza sativa var. glutinosa Blanco) Extract (BSRE) contains a high concentration of polyphenols, flavonoids, and anthocyanins with known antioxidant and hepatoprotective effects. Nevertheless, its clinical application is limited by poor water solubility and low bioavailability. This study is intended to develop and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) formulations of BSRE to enhance its antioxidant and hepatoprotective effects. The systems are characterized for their physicochemical properties and evaluated in vitro and in vivo in carbon tetrachloride (CCl₄)-induced liver damage in rats. Ethanolic maceration extraction was performed, followed by phytochemical and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS)/MS fingerprinting. SNEDDS was formulated with corn oil, Tween 80, and propylene glycol and optimized through pseudo-ternary phase diagrams. The optimized system was then adsorbed onto Neusilin® US2 to produce S-SNEDDS. Both systems were characterized for droplet size, emulsification time, zeta potential, and thermodynamic stability. Dissolution and antioxidant activity (DPPH assay) were measured in vitro , while in vivo efficacy was tested in the CCl₄-induced hepatotoxicity rat model. BSRE was found to have high cyanidin-3-O-glucoside (13.87 ± 0.12 mg/g) and quercetin (24.10 ± 1.34 mg/g) content. SNEDDS produced nano-sized droplets (~15 nm) with fast emulsification and enhanced solubility at pH 1.2, 4.5, and 6.8. Antioxidant activity was markedly improved in SNEDDS-BSRE (IC 50 : 32.6 µg/mL) compared to crude BSRE (IC 50 : 47.4 µg/mL). SNEDDS-BSRE at 100 and 200 mg/kg body weight (BW) significantly lowered serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), and bilirubin (BIL) and normalized albumin (ALB) level. Histopathological analysis confirmed reduced hepatic necrosis and inflammation. This investigation illustrates that SNEDDS-based delivery system profoundly improves the physicochemical stability, antioxidant activity, and hepatoprotective effect of BSRE, favoring its development as a functional nutraceutical. Additional pharmacokinetic and clinical studies are necessary to establish its translational feasibility.