TY - JOUR
T1 - Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone
T2 - optimization, characterization, pharmacokinetic, and hepatotoxicity studies
AU - Rathore, Charul
AU - Hemrajani, Chetna
AU - Sharma, Abhishek Kumar
AU - Gupta, Piyush Kumar
AU - Jha, Niraj Kumar
AU - Aljabali, Alaa A.A.
AU - Gupta, Gaurav
AU - Singh, Sachin Kumar
AU - Yang, Jen Chang
AU - Dwivedi, Ram Prakash
AU - Dua, Kamal
AU - Chellappan, Dinesh Kumar
AU - Negi, Poonam
AU - Tambuwala, Murtaza M.
N1 - Funding Information:
M/s Gattefosse, Saint-Priest, France, provided gift samples of Labrafil M 2125 CS, Labrafac Lipophile WL 1349, Labrafac PG, and Compritol 888 ATO to the authors. The authors are grateful to Shoolini University for supporting them with their research.
Publisher Copyright:
© 2022, The Author(s).
PY - 2023/1
Y1 - 2023/1
N2 - 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: [Figure not available: see fulltext.].
AB - 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: [Figure not available: see fulltext.].
KW - Bioavailability
KW - Hepato-toxicity
KW - In vitro release kinetics
KW - SNEDDS
KW - Thermodynamic stability
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U2 - 10.1007/s13346-022-01193-8
DO - 10.1007/s13346-022-01193-8
M3 - Article
C2 - 35831776
AN - SCOPUS:85134294479
SN - 2190-393X
VL - 13
SP - 292
EP - 307
JO - Drug Delivery and Translational Research
JF - Drug Delivery and Translational Research
IS - 1
ER -