Designing novel piperine-vanillin nano-crystals for bioavailability enhancement

Abstract

Piperine (PIP) exhibits various pharmacological effects including anti-inflammatory, antipyretic, anti-convulsant, and neuroprotective activity, but its poor water solubility and oral absorption limit its therapeutic uses. In the present study, nano-crystal technology was employed to enhance the dissolution rate and bioavailability of PIP. Piperine-vanillin (PIP-VN) nano-crystals were formulated by top-down and bottom-up techniques and evaluated both in vitro and in vivo. The results revealed that the PIP-VN nano-crystal exhibited an average particle size of 34.03 ± 0.51 nm. In the release study, PIP-VN nano-crystal performed 2.63-fold enhancement than PIP coarse powder. Upon oral administration, in the brain AUC0–24 of PIP-VN nano-crystal was significantly higher than PIP suspension. The brain/blood ratio of the drug for PIP-VN nano-crystal was higher than PIP suspension; indicating that administration of PIP-VN nano-crystal was superior for the delivery drug to the brain. PIP-VN nano-crystal showed AUC0–24 of 5.654 ± 0.230 ngh/mL in the brain which was more than PIP suspension (AUC0–24 of 2.025 ± 0.009 ngh/mL in the brain). From AUC data it may be concluded that brain delivery efficiency was improved using the nano-crystal approach. Compared with PIP coarse powder PIP-VN nano-crystals exhibit excellent performance in both in vitro and in vivo studies.