Self-assembled nanoscale entities: Preparative process optimization, payload release, and enhanced bioavailability of thymoquinone natural product

Abstract

Abstract Thymoquinone (TMQ), present in Nigella sativa L., exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties. Poor aqueous solubility, low oral bioavailability, hepatic first-pass metabolic constraints, and pH instability have limited TMQ’s in vivo use in clinical settings. This study designed and prepared thermodynamically stable, self-emulsified, nanoscale vesicles with the ternary diagram assistance to produce self-nanoemulsifying drug delivery system (SNEDDS). The TMQ-SNEDDS preparations used clove oil, isopropyl myristate (IPM) (1:1), Labrasol, and Transcutol-P. The SNEDDS mean droplet size varied between 72.85 and 98.42 nm, and approximately >70% TMQ was released within the first 4 h. The peak plasma concentration values of TMQSNE3 and TMQ suspension were 420.31 ± 35.23 and 98.51 ± 9.97 μg/mL, respectively, whereas time to achieve the peak plasma concentration values were 0.75 ± 0.12 and 1.0 ± 0.30 h, respectively. The area under the curve from time 0 to t (AUC0–t ) and the area under the moment curve from time 0 to t (AUMC0–t ) of TMQSNE3 were found to be 1838.63 ± 55.73 µg h/mL and 1909.59 ± 382.81 µg h/mL, respectively, which were highly significant (p < 0.05) in comparison with AUC0–t (389.36 ± 87.08 μg h/mL) and AUMC0–t (390.31 ± 184.55 μg h/mL) of the TMQ suspension. The relative bioavailability of TMQ was enhanced by 4.7-folds for the optimized TMQSNEDDS than that of the free drug suspension. The SNEDDS enhanced the bioavailability, which, in turn, positively affected the therapeutic efficacy of this naturally bioactive compound, TMQ, which has delivery and bioavailability problems owing to poor aqueous solubility.