Preparation, characterization, biodistribution, pharmacokinetics and pharmacodynamics of tanshinone Ⅱ A emulsion for intravenous administration
This study investigates emulsion as a potential parenteral drug delivery system for tanshinone ⅡA. The emulsion was prepared using injectable triglyceride as oil phase, soybean phospholipid as emulsifier and poloxamer 188 as coemulsifier. The emulsion had a spherical shape with a average size of 234nm, a zeta potential of -54.5mV, a drug-loading efficiency of 0.8mg/mL and a entrapment efficiency of 99.6％. There were no change in the size distribution, the zeta potential, the pH value, content of tanshinone ⅡA and physical appearance of the emulsion stored at 25℃ away from light during one year. The tanshinone ⅡA emulsion was applied for pharmacokinetics and biodistribution studies after intravenous administration. The plasma concentration-time data was best fitted with a two-compartment model, the pharmacokinetics of tanshinone ⅡA was characterized with a distribution half-life (t1/2α) of 0.14min, a terminal half-life (t1/2β) of 8.43min, a distribution volume (V) of 0.01L/kg, a plasma clearance (CL) of 0.033L/min/kg and an AUC0→∞ of 152.19μg.min/ml. After an i. v. dose of 10mg/kg to mice, tanshinone ⅡA tissue concentrations decreased in the order of liver>lung>plasma>brain>spleen>heart>kidney. Rats were intravenous administrated with tanshinone ⅡA emulsion at a dose of 1mg/kg/day for 4 days and then subjected to cerebral ischemia-reperfusion injury induced by a middle cerebral artery occlusion (MCAO). Tanshinone ⅡA-treated group was ameliorated in the neurological score (P<0.01) and decreased in cerebral infarct volume (P<0.05). The study demonstrates promising therapeutic potential for cerebral ischemia using the emulsion as a drug delivery system for tanshinone ⅡA.
tanshinone ⅡA emulsion biodistribution pharmacokinetics cerebral ischemia
MAO Sheng-jun LIANG Zhen JIN Hui BI Yue-qi LI Hui HOU Shi-xiang
West China School of Pharmacy, Sichuan University, Chengdu 610041, China The Hospital of Sichuan province, Change, Sichuan, China 610072, China
国际会议
上海
英文
316-322
2007-10-19（万方平台首次上网日期，不代表论文的发表时间）