A novel oil-body nanoemulsion formulation of ginkgolide B: pharmacokinetics study and in vivo pharmacodynamics evaluations.
The goal of this study was to develop a novel oil-body nanoemulsion (ONE) for Ginkgolide B (GB) and to conduct pharmacokinetics and pharmacodynamics evaluations. GB-ONE was prepared by O/O emulsion method. The differences in pharmacokinetics parameters and tissue distribution of rats after oral administrated with GB-ONE were investigated by liquid chromatography-tandem mass spectrometry. Changes in the ethological and pathological characterizations of the Alzheimer's disease rats after treated with GB-ONE were evaluated by Morris water maze (MWM) and pathological section, respectively. Furthermore, choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) activity in hippocampus was analyzed by spectrophotometric method. The results indicated that the AUC of GB in rats' plasma was significantly improved after incorporated into ONE, and GB-ONE was significantly targeted into brain. In MWM experiment, memory improvement of rats with cognition impaired was confirmed after administrated with GB-ONE. Furthermore, GB-ONE significantly inhibited AchE activity and enhanced the activity of ChAT in the hippocampus. The overall results implicated that the novel ONE was effective for improving the drawbacks of GB and showed great potential for clinical application.
The Pharmacokinetics Lab, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China; School of pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China; The Institute of Pharmacokinetics, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230038, China.
Pengfei
P
Yang
Xiaolei
X
Cai
Kai
K
Zhou
Chuanhua
C
Lu
Weidong
W
Chen
D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004655:Emulsions / Q000737:chemistry*; D046934:Ginkgolides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007783:Lactones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008568:Memory / Q000187:drug effects; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D004655:Emulsions; D046934:Ginkgolides; D007783:Lactones; D014677:Pharmaceutical Vehicles; C045856:ginkgolide B; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase
Alzheimer's disease; CNS; Ginkgolide B; amyloid β25-35; blood brain barrier; nanoemulsion; pharmacodynamics; pharmacokinetics