摘要
目的:研究灌胃(ig)给予雷洛昔芬(raloxifene,RAL)混悬剂(suspensions)和纳米乳(nanoemulsion,NE)后,大、小鼠口服吸收及小鼠组织分布特性。方法:大鼠静脉注射(iv)RAL溶液(10 mg·kg^(-1)),大、小鼠ig给予RAL混悬剂和纳米乳(60 mg·kg^(-1)),于给药后不同时间点取得大、小鼠血样及小鼠组织样品,HPLC法测定生物样品中RAL浓度,比较混悬剂和纳米乳ig给药后的口服吸收参数和组织分布特点。结果:口服吸收研究中,与混悬剂组相比,雷洛昔芬纳米乳(RAL-NE)在大、小鼠体内的AUC和Cmax均增大;小鼠组织分布研究中,2种制剂中的RAL在肺中的药物分布较高;脾的AUC和Cmax提高最为明显,而肝的AUC和Cmax2种制剂相比几乎没有差别。结论:与混悬剂相比,RAL-NE可以在一定程度上提高RAL的生物利用度;RAL制成纳米乳后体内靶向性发生了一定的改变,对脾具有明显的靶向性。
Objective： To investigate the oral absorption in rats and tissue distribution in mice of raloxifene（ RAL） nanoemulsion（ NE） and raloxifenen suspension after oral administration. Methods： The plasma and tissue samples were collected from rats or mice at different time points post-dose for oral studies（ a single dose of 60mg·kg-1） or intravenous injection studies（ a single dose of 10 mg·kg-1）. An HPLC method was established to determine the concentrations of RAL in plasma of rats and tissues of mice then the characteristics of oral absorption and tissue distribution were compared. Results： In the oral absorption studies in rats and mice,the main oral absorption parameters such as the AUC and Cmaxof RAL-NE were significantly increased compared with the suspension.In the tissue distribution studies,the distribution of RAL was highest in the lungs for both nanoemulsion and suspension;the AUC and Cmaxof RAL in the spleen were increased significantly,but they were almost the same in the liver compared with the suspension. Conclusion： Compared with RAL suspension,RAL-NE was able to improve the oral bioavailability of RAL to a certain extent. The targeting property of RAL loaded in nanoemulsion was changed,which was obviously targeted to spleen.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2017年第8期923-929,共7页
Chinese Journal of New Drugs
基金
国家自然科学基金资助项目(81573353)
关键词
雷洛昔芬
纳米乳
口服吸收
组织分布
生物利用度
raloxifene
nanoemulsion
oral absorption
tissue distribution
bioavailability
