Lv Wenli, Guo Jianxin, Li Jin, Wang Xueliang, Li Jianying, Ping Qineng
School of Pharmacy, China Pharmaceutical University, Nanjing, PR China.
Drug Dev Ind Pharm. 2006 Mar;32(3):309-14. doi: 10.1080/03639040500518880.
The purpose of the study was to prepare the unilamellar liposomal vesicles of breviscapine (Breviscapine-LUVs) and investigate the pharmacokinetics of Breviscapine-LUVs in rabbits. Breviscapine-LUVs were prepared by the film dispersion method and treated further by extrusion. Its size distribution and zeta potential were determined by photon correlation spectroscopy. The encapsulation efficiency (EE) and cumulative release of Breviscapine-LUVs were assayed by the dialysis method. The crossover design (two periods) was used in six rabbits, which were administered Breviscapine-LUVs and reference preparation. Results showed that the particle size of Breviscapine-LUVs was 50.8 nm, and the polydispersity index was 0.287. The zeta potential was -24 mV +/- 9 mV (n = 3), and the EE% was 81.1 +/- 1.1% (n = 3). The cumulative release of vesicles in 0.9% NaCl was 17.2 +/- 0.78%, 26.1 +/- 0.68%, and 29.9 +/- 0.81% in 2, 8, and 24 h, respectively. The mean concentration-time curves of breviscapine liposomes and reference preparation were both fitted to a two-compartment model with the main pharmacokinetic parameters as follows: t(1/2beta) of Breviscapine-LUVs and reference preparation were (42.5 +/- 28.6) min and (6.01 +/- 4.64) min, respectively; CL((s)) were (15.3 +/- 9.03) mL x min(-1) and (84.6 +/- 40.6) mL x min(-1), respectively; AUC(0-300) were (1267 +/- 1083) microg x min x mL(-1) and (196 +/- 107) microg x min x mL(-1), respectively. Compared with the reference preparation, breviscapine liposomes had a much higher concentration in plasma and contained characteristic of sustained-release, which ameliorated the pharmacokinetic properties of scutellarin.
本研究的目的是制备灯盏花素单层脂质体囊泡（灯盏花素 - LUVs），并研究灯盏花素 - LUVs在兔体内的药代动力学。采用薄膜分散法制备灯盏花素 - LUVs，并通过挤压进一步处理。通过光子相关光谱法测定其粒径分布和zeta电位。采用透析法测定灯盏花素 - LUVs的包封率（EE）和累积释放率。采用交叉设计（两个周期）对6只兔进行实验，分别给予灯盏花素 - LUVs和参比制剂。结果显示，灯盏花素 - LUVs的粒径为50.8 nm，多分散指数为0.287。zeta电位为 -24 mV ± 9 mV（n = 3），EE%为81.1 ± 1.1%（n = 3）。囊泡在0.9%氯化钠中的累积释放在2、8和24 h分别为17.2 ± 0.78%、26.1 ± 0.68%和29.9 ± 0.81%。灯盏花素脂质体和参比制剂的平均浓度 - 时间曲线均符合二室模型，主要药代动力学参数如下：灯盏花素 - LUVs和参比制剂的t(1/2β)分别为(42.5 ± 28.6) min和(6.01 ± 4.64) min；CL(s)分别为(15.3 ± 9.03) mL·min⁻¹和(84.6 ± 40.6) mL·min⁻¹；AUC(0 - 300)分别为(1267 ± 1083) μg·min·mL⁻¹和(196 ± 107) μg·min·mL⁻¹。与参比制剂相比，灯盏花素脂质体在血浆中的浓度更高，具有缓释特性，改善了灯盏乙素的药代动力学性质。
