灯盏花素纳米混悬剂的制备及其大鼠体内药动学研究

摘要

AIM:Nanosuspension was used to improve the oral bioavailability of breviscapine. METHODS: The breviscapine nanosuspension was prepared by emulsification-diffusion. Its PCS size was 293.11±55.86 nm,Zeta-potential was 27.5±4.9 mV. The solubility and dissolution of breviscapine was determined by ultrafiltration. RESULTS: The solubility and dissolution of breviscapine were remarkably increased by the nanosuspension. Pharmacokinetic behavior of the breviscapine nanosuspension in rats was investigated compared with the coarse suspension. The absolute bioavailability was increased from 1.3±0.9% to 14.4±3.7% and MRT extended from 4.1±1.4 h to 8.6±1.8 h. CONCLUSION: The transporting characteristics of nanoparticles in intestine was a more critical factor for improving bioavailability of breviscapine than the solubility.%目的:应用纳米混悬剂提高难溶性药物灯盏花素的口服生物利用度.方法:采用自乳化溶剂扩散工艺制备了灯盏花素纳米混悬剂.所得纳米混悬剂PCS粒径为(293.11±55.86) nm,Zeta电位为(27.5±4.9) mV;建立以超滤法测定灯盏花素纳米混悬剂溶解度和溶出度的方法,并以该法进行了灯盏花素溶解度和溶解速度的考察.结果:纳米混悬剂显著提高了灯盏花素的溶解度和溶解速度;进行了灯盏花素纳米混悬剂及粗混悬剂大鼠体内的药动学研究,纳米混悬剂显著提高了灯盏花素在大鼠体内的生物利用度并延长了其作用时间,其大鼠灌胃绝对生物利用度从(1.3±0.9)%提高到(14.4±3.7)%,MRT从(4.1±1.4) h延长到(8.6±1.8) h.结论:纳米混悬剂的肠道转运行为是提高生物利用度的关键因素.