紫杉醇长循环脂质体制备及其药动学探究.docVIP

紫杉醇长循环脂质体制备及其药动学探究摘要：目的制备紫杉醇长循环脂质体并观察其在大鼠体内的药动学。方法用薄膜分散法制备紫杉醇长循环脂质体；HPLC法测定血浆中紫杉醇的药物浓度；用3P97程序计算药动学参数。结果脂质体粒径为（106.5±1.7）nm，包封率为（87.5±2.5）%，紫杉醇长循环脂质体和紫杉醇注射液的血药浓度-时间曲线均符合二室模型，药动参数t1/2β分别为（7.32±1.24）h和（0.32±0.06）h，AUC分别为（23.85±1.20）μgh?mL-1和（5.08±0.45）μgh?mL-1。结论与紫杉醇注射液相比，紫杉醇长循环脂质体显著延长了紫杉醇在血液循环系统中的驻留时间，具有长效作用。 关键词：紫杉醇；长循环脂质体；包封率；药动学 中图分类号：R946文献标识码：A文章编号：1672-979X(2009)-01-0014-04 Preparation of Long-circulating Paclitaxel-containing Liposomes and Its Pharmacokinetics ZHANG Zi-yu1, JIA Li-jun2, GONG Jian-gang3, LI Guang-zhou4, KANG Bai1* (1. Department of Pharmacology, Weifang Medical University, Weifang 261042, China; 2. Beijing Tongren Hospital affiliated to Capital Medical University, Beijing 100730, China; 3. College Of Traditional Chinese Veterinary Medicine, Hebei Agricultural University, Dingzhou 073000, China; 4. Department of Nuclear Medicine, Affiliated Hospital of Weifang Medical University, Weifang 261042, China) Abstract：Objective To prepare the long-circulating paclitaxel-containing liposomes and evaluate its pharmacokinetics in rats. Methods The long-circulating paclitaxel-containing liposomes were prepared by film dispersion method. The concentration of paclitaxel in rats?plasma was determined by HPLC method and the parameters were calculated with 3P97 program. Results The mean diameter of liposomes was (106.5±1.7) nm and the entrapment efficiency was (87.5±2.5) %. The plasma concentration-time curves of long-circulating paclitaxel-containing liposomes and paclitaxel injection were both fit to the two-compartment model and the pharmacokinetic parameters were (7.32±1.24) h and (0.32±0.06) h for t1/2β,(23.85±1.20) μg?h?mL-1 and (5.08±0.45) μg ?h?mL-1 for AUC, respectively. Conclusion Compared with paclitaxel injection, the long-circulating paclitaxel-containing liposomes can significantly prolong the resident time of paclitaxel in the blood circulating system, and has a prolonged action. Key words：paclitaxel; long-circulating liposom