Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies

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.

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Materials

TQ was purchased from M/s Nice Chemicals Pvt. Ltd., Cochin, India. Other reagents, namely, sodium dihydrogen phosphate, potassium dihydrogen phosphate, and sodium hydroxide (NaOH), were made available from Sigma-Aldrich, Mumbai, India. Labrafil M 2125 CS, Labrafac Lipophile WL 1349, Labrafac PG, Labrafil, and Compritol 888 ATO were received ex gratia from M/s Gattefosse, Saint-Priest, France. M/s Merck Specialties Pvt. Ltd. India supplied ethanol (EtOH) and hydrochloric acid (HCl). Span 80 and Tween 80 were obtained from M/s Qualikem Fine Chemicals Pvt. Ltd. Vadodara, India. Glyceryl monostearate (GMS) and stearic acid were obtained from Hi-Media Pvt. Ltd., Mumbai, India.

Rathore, C., Hemrajani, C., Sharma, A.K. et al. Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies. Drug Deliv. and Transl. Res. (2022).
https://doi.org/10.1007/s13346-022-01193-8