Abstract
The present study aimed to develop a nanoparticle (NP) formulation of thymoquinone (TQ), a potent anti-oxidant chemical, with use of a cold wet-milling (CWM) system to improve its dissolution behavior and pharmacokinetic properties. The NP formulation of TQ (TQ/CWM) was prepared by CWM system, and its physicochemical properties were characterized in terms of particle size distribution, morphology, crystallinity, and dissolution. The photochemical properties of TQ were also examined upon UV/VIS absorption, reactive oxygen species (ROS) generation, and photostability. Pharmacokinetic studies were carried out in rats. Application of the CWM system to TQ led to successful development of nano-sized TQ. The mean diameter of TQ in TQ/CWM was calculated to be 143nm, and TQ particles in TQ/CWM were found to be amorphous. There was a marked improvement in dissolution rate compared with TQ. TQ showed significant generation of singlet oxygen and superoxide upon exposure to simulated sunlight, suggesting its high photoreactivity, and solid samples such as TQ and TQ/CWM exhibited higher photostability than TQ solution. In comparison with TQ, enhanced TQ exposure was observed with a ca. 6-fold increase of oral bioavailability, and the Tmax was shown to be a quarter. From these findings, the NP approach employing the CWM system might be a promising dosage option for improving the nutraceutical values of TQ.
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