【作者】 张馨欣； 潘卫三； 甘勇； 朱春柳； 张建媛；

【Author】 Zhang Xin-xin1,2, Pan Wei-san1, Gan Yong2*, Zhu Chun-liu2, Zhang Jian-yuan1 (1. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; 2.Shanghai Institute of Materia Medica Chinese Academy of Sciences, Shanghai 201203, China)

【机构】 沈阳药科大学药学院； 中国科学院上海药物研究所；

【摘要】 目的以单硬脂酸甘油酯为载体材料制备羟基喜树碱长循环纳米脂质载体,并考察其体内外性质。方法采用“熔融乳化-高压均质法”制备以PEG40硬脂酸酯及PEG100硬脂酸酯修饰的纳米脂质载体(PEG40-NLC及PEG100-NLC);测定PEG40-NLC及PEG100-NLC的开环百分率及固定水化层厚度;考察二者的体外释放及大鼠体内的药动学参数。结果PEG40-NLC及PEG100-NLC具有稳定羟基喜树碱内酯结构的作用,固定水化层厚度分别为2.01nm和4.81nm。二种制剂体外释放呈缓释特征,经大鼠尾静脉注射后的消除半衰期分别为1.63和5.34h,具有长循环效果。结论长循环纳米脂质载体可稳定羟基喜树碱的内酯型结构,延长药物在中央室的循环时间。更多还原

【Abstract】 OBJECTIVE To prepare long-circulating nanostructrued lipid carries (NLC) containing hydroxycamptothecin with monostearin and investigate the in vitro and in vivo characterization of them. METHODS PEG40 stearate and PEG100 stearate modified NLC (PEG40-NLC, PEG100-NLC) were prepared by melt emulsification and homogenization technique. The fixed aqueous layer thickness (FALT) of NLC and percent of HCPT lactone form was calculated. The release of HCPT in vitro and pharmacokinetics after iv were studied. RESULTS Stability of HCPT lactone form in NLC was increased. The FALTs of them were 2.01nm and 4.81nm, respectively. The PEG40-NLC and PEG100-NLC release HCPT slowly, 79.0% and 59.0% of total drug released with 48h, respectively. PEG40-NLC and PEG100-NLC behaved long-circulation feature, and the elimination half-life of them were 1.63 and 5.34h. CONCLUSION Long-circulating NLC containing stable HCPT lactone form has been obtained.更多还原