摘要
目的研究9-硝基喜树碱纳米脂质载体系统的体外释放、巨噬细胞摄取及体内组织分布特性。方法以BLB/C小鼠腹腔巨噬细胞为细胞模型进行9-硝基喜树碱纳米脂质载体系统的体外细胞吞噬实验;以一级昆明种小鼠为动物模型进行体内组织分布实验;并进行多晶X-射线衍射及体外释放实验的测定。结果9-硝基喜树碱可能以无定形物分散在纳米脂质载体中,液态脂质的加入并没有改变纳米粒固态内核的性质;体外释放实验表明纳米脂质载体系统具有一定的缓释特性;PEG的修饰使巨噬细胞对纳米粒的摄取减少,且能够增强纳米粒抵抗蛋白吸附的能力;纳米脂质载体系统能够延长9-硝基喜树碱在血中的滞留时间,并改变其在小鼠体内的分布特征。结论由Myrj59制备的纳米脂质载体系统具有缓释特性,且具有良好的长循环性及肝、肺靶向性。
Aim To study the release and cell uptake characteristics of 9-nitrocamptotheein （9-NC） nanostruetured lipid carrier system （NLC） in vitro and its tissue distrihution characteristics in vivo. Methods Mouse peritoneal macrophagcs were used to investigate the uptake of nanopartieles by cells in vitro. The tissue distribution of 9-nitrocamptothecin solution and stealth nanostruetured lipid carrier system （S-NLC） was determined aider inlravenous administration to mice at a single dose of 1.5 mg ·kg^-1. The release and erystalloid characteristics were also investigated. Results X-ray diffraction spectrum showed that 9-NC prohahly was amorphous in S-NLC. The liquid lipid did not change the characteristics of the solid matrix in nanoparticles. The in vitro release and cell uptake characteristics of stealth and non-stealth 9-NC-NLC were investigated, separately. The results showed that the stealth 9-NC-NLC had sustained- release characteristics and could resist the absorption effect of the additional plasmas to a certain extent. In addition, the cell uptake percentage of stealth 9-NC-NLC was llluch lower than that of the non-stealth ones. The tissues distribution results showed that 9-NC in the S-NLC was mainly found in the lung, liver, pancreas and ovary/uterus, while the quantity of 9-NC was much lower in heart and kidney. The AUQo_, of S-NLC in hlood, ovary/uterus, pancreas, liver and lung were higher than that of 9-nitrocamptothecin solution. The weight-average drug targeting efficiency （ Te^ ＊ ） of S-NLC in liver and lung were significantly higher than that of 9-nitrocamptothecin solution. The mean residence times （MRT） of S-NLC was 44 h, while that of 9-nitrocamptothecin solution was 8 h. Therefore, S-NLC showed obvious targeting effects on liver and lung. Conclusion S-NLC with PEG flexible chains has sustained-release characteristics and can prolong its circulation in blood and have good targeting efficiency on liver and lung.
出处
《药学学报》
CAS
CSCD
北大核心
2005年第11期970-975,共6页
Acta Pharmaceutica Sinica
关键词
9-硝基喜树碱
纳米脂质载体
吞噬作用
组织分布
9-nitrocamptotheein
nanostruetured lipid carrier
phagoeytosis
tissue distribution
作者简介
通讯作者 Tel：86-21-54237432，E-mail：xlfang@shmu.edu．cn
