Preparation and Physicochemical and Pharmacokinetic Characterization of Ginkgo Lactone Nanosuspensions for Antiplatelet Aggregation

Abstract

The aim of this study was to investigate the potential of nanosuspensions (NSs) in improving the dissolution and absorption of poorly water-soluble ginkgo lactones (GLs), including ginkgolide A, ginkgolide B, and ginkgolide C. Liquid GL-NSs were prepared by a combined bottom-up and top-down approach with response surface methodology design, followed by freeze-drying solidification. Physicochemical characterization of the prepared freeze-dried GL-NSs was performed by photon correlation spectroscopy, scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. In vitro dissolution and in vivo bioavailability of ginkgolide A, ginkgolide B, and ginkgolide C in freeze-dried GL-NSs were evaluated with GLs coarse powder as control. Their inhibitory effects on platelet aggregation were also comparatively analyzed. GLs existed in an amorphous state in the prepared freeze-dried GL-NSs. The particle size, polydispersity index, zeta potential, and redispersibility index of freeze-dried GL-NSs were around 286 nm, 0.26, -25.19 mV, and 112%, respectively. The particle size reduction resulted in much more rapid and complete dissolution of ginkgolides from GL-NSs than coarse powder. Comparison with GLs coarse powder, freeze-dried GL-NSs showed a significant decreased Tmax, 2-fold higher peak concentration, and 2-fold higher area under plasma concentrations curve for 3 ginkgolides and exhibited significantly higher antiplatelet aggregation effect.

Keywords: bioavailability; dissolution; drug transport; nanotechnology; oral absorption; oral drug delivery; pharmacodynamics; pharmacokinetics; physical characterization; stabilization.