Novel breviscapine nanocrystals modified by panax notoginseng saponins for enhancing bioavailability and synergistic anti-platelet aggregation effect.

Abstract

Breviscapine (BVP) is a flavonoid compound with strong neuroprotective and anti-platelet aggregation effect. The objective of this study is to design novel BVP nanocrystals modified by natural panax notoginseng saponins (PNS) for enhancing dissolution and anti-platelet aggregation effect of BVP. BVP nanocrystals modified by PNS (BVP-NC/PNS) were firstly prepared by coupling homogenization technology and freeze-drying technology, and BVP nanocrystals modified by RH40 (BVP-NC/RH40) as reference for comparison. The morphology, crystals characterization, dissolution behavior and anti-platelet aggregation effect of BVP-NC/PNS was systemically evaluated. The results demonstrated that the PNS could effectively maintain stability of BVP-NC at suspensions state dependent of its surface activity and the electrostatic repulsion effect. Combination of PNS and trehalose could prevent the aggregation of BVP-NC/PNS during freeze-drying. The PXRD and DSC results demonstrated that the BVP crystal state in BVP-NC/PNS was not changed owing to PNS modification and homogenization treatment. And the freeze-dried BVP-NC could easily recover back to BVP-NS and significantly improve the dissolution of BVP. The AUC(0-∞) of the BVP-NC/PNS was 4.54 times as high as that of the coarse BVP, but not significantly different compared to that of BVP-NC/RH40 (p < 0.05). The anti-platelet aggregation results demonstrated that, BVP-NC/PNS group showed more effective inhibition on PAF-induced platelet aggregation compared with corresponding control groups, which might attribute to the enhanced bioavailability of BVP and synergistic effect of PNS with BVP. In conclusion, PNS could be used as an alternative stabilizer for preparation of BVP-NC, and BVP-NC modified by PNS is a promising formulation strategy for enhancing oral bioavailability and anti-platelet aggregation of BVP.