Department of Pharmacy, Nanjing University of Traditional Chinese Medicine, Nanjing, People's Republic of China.
J Drug Target. 2010 Sep;18(8):627-36. doi: 10.3109/10611861003639788.
The purpose of this study was to develop and study the behaviors of bifendate (DDB) liposome in vivo. DDB liposome was prepared by the rotary evaporationextrusion method. The particle size, zeta-potential, encapsulation efficiency (EE), and in vitro drug release from liposome were determined and the in vivo studies were tested in mice and rats. The concentrations of DDB in plasma and liver at different sampling time points were determined by RP-HPLC. The liver concentration-time curves of DDB liposome and free drug solution in mice were determined, and the pharmacokinetic parameters in rats and mice were calculated and compared by statistical analysis. The average liposome diameter was 323 +/- 29 nm (n = 3) and the EE was 91.52 +/- 2.38%. There were significantly different parameters of k10 and area under the plasma concentrationtime curve (AUC(0-T)) between liposome and solution. The mean residence time (MRT(0-T)) in plasma of liposomal formulation was 3.72 times longer than that of solution. Compared with solution, DDB liposome delivered about 2.57 times higher DDB into liver. Thus, an optimum intravenous liposome formulation for DDB could be developed as an alternative to the commercial DDB preparations.
本研究旨在开发和研究双丹酯（DDB）脂质体的体内行为。采用旋转蒸发挤出法制备 DDB 脂质体。测定了脂质体的粒径、Zeta 电位、包封率（EE）和体外药物释放，并在小鼠和大鼠中进行了体内研究测试。采用反相高效液相色谱法（RP-HPLC）测定不同时间点血浆和肝脏中 DDB 的浓度。测定了 DDB 脂质体和游离药物溶液在小鼠体内的肝浓度-时间曲线，并通过统计分析计算和比较了大鼠和小鼠的药代动力学参数。平均脂质体直径为 323 ± 29nm（n=3），EE 为 91.52 ± 2.38%。脂质体与溶液之间的 k10 和血浆浓度-时间曲线下面积（AUC（0-T））参数有显著差异。脂质体在血浆中的平均驻留时间（MRT（0-T））比溶液长 3.72 倍。与溶液相比，DDB 脂质体将约 2.57 倍的 DDB 递送到肝脏。因此，可以开发出一种优化的 DDB 静脉内脂质体制剂，作为商业 DDB 制剂的替代品。
