Preparation, characterization, biodistribution, pharmacokinetics and pharmacodynamics of tanshinone Ⅱ A emulsion for intravenous administration

摘要

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°C 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.