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