Optimized piperine–phospholipid complex with enhanced bioavailability and hepatoprotective activity

Abstract

Piper species is one of the most widely consumed spices for culinary purposes. Piperine (PIP) present in Piper species has a wide range of therapeutic activity including hepatoprotection. However, the major biological limitation of PIP is its low bioavailability after oral administration. Purpose of the study was to prepare an optimized and adequately characterized PIP–phospholipid complex (PPC) as a delivery system to overcome these limitations and to investigate the pharmacokinetics and hepato-protectivity of the formulation in the animal model. Response surface methodology was adopted to optimize the process parameters for PPC preparation. FT-IR, DTA, PXRD, SEM, molecular docking etc. were used for characterization. Solubility, log P, dissolution efficiency and in vivo pharmacokinetics were also investigated. PPC showed enhanced hepatoprotective potential as compared to pure PIP at the same dose level (25 and 50 mg/kg). PPC restored the levels of serum marker and antioxidant enzymes. PPC also increased the bioavailability of PIP in rat serum by 10.40-fold in comparison with pure PIP at the same dose level and enhanced the elimination half-life (t_{1/2 el}) from 0.477 ± 1.76 to 9.80 ± 1.98 h. Results concluded that PPC enhanced the hepatoprotection of PIP which may be due to the improved bioavailability and pharmacokinetics of PIP in rats.

Graphical Abstract

Keywords:

• Piperine
• phosphatidylcholine complex
• bioavailability
• hepatoprotective
• pharmacokinetics
• molecular docking

Acknowledgements

The authors are thankful to the Institute of Bioresources and Sustainable Development, a National institute under Dept of Biotechnology (DBT), Government of India, Imphal, India for necessary help and support. Thanks are due to DBT for financial support through Tata Innovation fellowship program (Vide: D.O. No. BT/HRD/3501/04/2014) to Pulok K Mukherjee.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

Thanks are due to DBT for financial support through Tata Innovation fellowship program [Vide: D.O. No. BT/HRD/3501/04/2014] to Pulok K Mukherjee.