Preparation and Pharmacokinetics in Rabbits of Breviscapine Unilamellar Vesicles

ABSTRACT

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 zata 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_1/2β 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 × min⁻¹ and (84.6 ± 40.6) mL × min⁻¹, respectively; AUC_0–300 were (1267 ± 1083) μg × min × mL⁻¹ and (196 ± 107) μg × min × 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.

KEYWORDS:

• Breviscapine
• Scutellarin
• Liposomes
• Vesicles
• Dialysis
• Phamacokinetics