Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs

ABSTRACT

Background: The poor biopharmaceutical properties of thymoquinone (TQ) obstruct its development as a hepatoprotective agent. To surmount the delivery challenges of TQ, phospholipid nanoconstructs (PNCs) were constructed.

Method: PNCs were constructed employing microemulsification technique and systematic optimization by three-factor three level Box-Behnken design.

Result: Optimized PNC composition exhibited nano size (<100 nm), spherical morphology, within acceptable range of polydispersity index (0.55), high drug entrapment efficiency (>90%), controlled drug release pattern, and neutral surface charge (zeta potential of −0.65 mV). After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-vis plain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vis pure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.

Conclusion: TQ-loaded PNCs can be efficient nano-platforms for the management of hepatic disorders and promising drug delivery systems to enhance oral bioavailability of this hydrophobic molecule.

KEYWORDS:

• Thymoquinone
• box-Behnken design
• lipid carriers
• microemulsifcation
• hepatotoxicity
• pharmacokinetics

Acknowledgments

The authors are thankful to M/s Phospholipid GmbH, Nattermannallee, Germany, for the ex gratis supply of PL90G, and M/s Gattefosse, Saint-Priest, France, for providing the gift samples of Labrafac, Compritol 888 ATO and Labrafil. The authors are also thankful to Shoolini University for facilitating the research work.

Author contributions

C. Rathore carried out the study, helped in compilation of the data, manuscript writing and editing. N. Upadhyay helped in conducting experimental work and interpreting analytical data. R. Kaundal helped in editing and analysis of the data. R.P. Dwivedi helped in editing the data. S. Rahatekar and A. John helped in revising the manuscript. K. Dua helped in interpretation of the data and checked the first draft of the prepared manuscript. M. Tambuwala helped in revising the manuscript. S. Jain and D. Chaudhari helped in interpreting data and revising the manuscript. P. Negi conceptualized, planned, supervised the study, analyzed, interpreted the data and edited the manuscript. All authors have read and approved the manuscript for publication

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

The research work was funded by Shoolini University of Biotechnology and Management Sciences.