Enhancing both oral bioavailability and brain penetration of puerarin using borneol in combination with preparation technologies

Now there are few good oral preparations of puerarin used in cerebrovascular diseases because of its poor oral absorption caused by the low water solubility and the poor penetration into brain. In this study, three oral formulations of puerarin, nanocrystals suspension (NCS), inclusion compounds solution (ICS) and self-microemulsifying drug delivery system (SMEDDS) were prepared with borneol as an oral brain-targeting enhancer. A rat syngeneic in vitro model of the brain–blood barrier (BBB) was established to investigate effects of borneol on the permeability of puerarin across the BBB. The pharmacokinetics of puerarin in mice after oral administration was investigated by a high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) method. The in vitro BBB model study showed the permeability of puerarin was increased significantly (p < 0.05) and the value of transepithelial electrical resistance at 2 h was decreased significantly (p < 0.01) when the concentration of borneol was over 12.5 μg/mL compared with the control group. The pharmacokinetics results indicated borneol with doses of over 50 mg/kg could obviously increase both intestinal absorption and brain penetration of puerarin. With co-administration of borneol (100 mg/kg), the AUC of puerarin both in plasma (AUC(plasma)) and in brain (AUC(brain)) for SMEDDS were significantly higher than those for NCS (p < 0.01) and ICS (p < 0.05). These results suggested borneol in combination with SMEDDS could improve both the oral absorption and the brain penetration of puerarin in mice, which was promising for the development of an oral formulation of puerarin used in cerebrovascular diseases.