Preparation, characterization and pharmacokinetics of oridonin-loaded liposomes.

The aim of this study was to prepare the oridonin liposomes and evaluate the physicochemical characteristics and pharmacokinetics in rats. A three-level three-factor Box-Behnken Design was used to optimize the preparation of oridonin liposomes. A highly sensitive high performance liquid chromatographic quantification method with ultraviolet detection was established and validated for the determination of oridonin in rat plasma. Twelve Sprague-Dawley rats were randomly assigned to inject with 15 mg/kg of oridonin or oridonin liposomes via the tail vein. Pharmacokinetic parameters were estimated using a compartmental modelling approach by PKsolver software. The optimum conditions were as follow: soybean phospholipids/cholesterol ratio of 3.9:1, soybean phospholipids/drug ratio of 8.5:1, and soybean phospholipids concentration of 1.1%. Under these conditions, the mean particles size, polydispersity index, zeta potential and encapsulation efficiency of oridonin liposomes were 170.5 nm, 0.246, -30.3 mV, and 76.15%, respectively. The pharmacokinetic results showed that liposomes could significantly prolong the elimination half-life (from 2.88±0.55 to 13.67±3.52 h), increase area under the concentration-time curve (from 1.65±0.17 to 6.22±0.83 μg·h/ml), and decrease the clearance (from 6.62±1.38 to 1.96±0.24 l/kg·h). The oridonin liposomes increased the elimination half-life and area under the concentration-curve and offer a reference for the development of drugs with short half-life.