Development and pharmacokinetics of nimodipine-loaded liposomes.
In order to improve the water solubility of nimodipine and prolong the time of the drug in the circulation, nimodipine-loaded liposomes with a small size and high entrapment efficiency were prepared by a method that was easy to scale up (the modified ethanol injection method). The nimodipine liposome dispersions were characterized with respect to particle size distribution, zeta potential and entrapment efficiency. Liposomal nimodipine and nimodipine solution were intravenously administered to mice as a single dose of 4 mg kg-1. The pharmacokinetic parameters of nimodipine changed significantly when encapsulated in liposomes. The clearance of nimodipine encapsulated in liposomes was reduced and the elimination half-life was prolonged. The ratios of the area under the curve values of nimodipine liposomes to nimodipine solution were 1.78 and 1.90 in plasma and cerebral tissue, respectively. The drug concentration in cerebral tissue and in plasma showed a good linear correlation, which showed that liposomes could efficiently deliver nimodipine into brain tissue. These findings suggest that intravenous administration of liposomal nimodipine produces higher and more stable plasma and cerebral drug concentrations compared with nimodipine solution. In conclusion, liposomal nimodipine is a promising alternative to the solution preparation.
Wang
Zhixuan
Z
Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China. wngzhixuan@yahoo.com
Deng
Yingjie
Y
Zhang
Xiaopeng
X
Wang
Ting
T
Wu
Fenglan
F
D000818:Animals; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D006207:Half-Life; D007275:Injections, Intravenous; D008081:Liposomes; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009553:Nimodipine / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D015203:Reproducibility of Results; D012995:Solubility; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D008081:Liposomes; D012996:Solutions; D009553:Nimodipine