title: 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.
authors: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Tian-Qi
authors: TQ
authors: Rui
authors: State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, 230036, China.
authors: Liang
authors: L
authors: Zhang
authors: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Hong-Zhi
authors: HZ
authors: Qiao
authors: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Ping
authors: P
authors: Huang
authors: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 210009, China.
authors: Shuai
authors: S
authors: Qian
authors: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: lijunsong1964@163.com.
authors: Jun-Song
authors: JS
authors: Li
authors: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Zhi-Peng
authors: ZP
authors: Chen
authors: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Ting-Ming
authors: TM
authors: Fu
authors: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Provincial TCM Engineering Technology Research Center of High Efficient Drug Delivery System (DDS), Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Liu-Qing
authors: LQ
authors: Di
authors: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors: Baochang
authors: B
authors: Cai
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005612:Freeze Drying; D020441:Ginkgo biloba / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D049329:Nanostructures; D010316:Particle Size; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013535:Suspensions
chemical_list: D007783:Lactones; D010975:Platelet Aggregation Inhibitors; D013535:Suspensions
keywords: bioavailability; dissolution; drug transport; nanotechnology; oral absorption; oral drug delivery; pharmacodynamics; pharmacokinetics; physical characterization; stabilization