Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (< 90 nm). Zeta potential was measured to be −11.35 mV, signifying the high stability of the oil droplets. In vivo pharmacokinetic evaluation showed a fourfold increase in the bioavailability of TQ-SNEDDS over pure TQ. Furthermore, in a PCM-induced animal model, TQ-SNEDDS demonstrated significant (p < 0.05) hepatoprotective activity compared to pure TQ and silymarin. Reduction in liver biomarker enzymes and histopathological examinations of liver sections further supported the results. In this study, SNEDDS was demonstrated to be an improved oral delivery method for TQ, since it potentiates hepatotoxicity and enhances bioavailability.

Graphical abstract

中文翻译：

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自纳米乳化药物递送系统 (SNEDDS) 介导提高百里醌的口服生物利用度：优化、表征、药代动力学和肝毒性研究

百里醌 (TQ) 是一种抗氧化剂、抗炎剂和保肝化合物，从黑种草的黑籽油中提取. 然而，高疏水性、较高 pH 水平下的不稳定性、光敏性和低口服生物利用度阻碍了其向靶组织的递送。使用微乳化技术制备了自纳米乳化药物递送系统（SNEDDS）来解决这些问题。对其物理化学性质、热力学稳定性研究、药物释放动力学、体内药代动力学和保肝活性进行了评估。液滴尺寸在纳米范围内 (< 90 nm)。Zeta 电位测得为 -11.35 mV，表明油滴的稳定性高。体内药代动力学评估表明，与纯 TQ 相比，TQ-SNEDDS 的生物利用度增加了四倍。此外，在 PCM 诱导的动物模型中，TQ-SNEDDS 表现出显着的 ( p < 0.05) 与纯 TQ 和水飞蓟素相比的保肝活性。肝脏生物标志物酶的减少和肝切片的组织病理学检查进一步支持了结果。在这项研究中，SNEDDS 被证明是一种改进的 TQ 口服给药方法，因为它增强了肝毒性并提高了生物利用度。

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