Oleanolic acid nanosuspensions: preparation, in-vitro characterization and enhanced hepatoprotective effect
Oleanolic acid nanosuspensions: preparation, in-vitro characterization and enhanced hepatoprotective effect
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DOI：
10.1211/0022357055407
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发表时间：
2005-02-01
影响因子：
3.3
通讯作者：
Xu, HB
中科院分区：
文献类型：
--
作者：
Chen, YJ;Liu, J;Xu, HB
油酸是一种天然三萜类化合物，在我国临床上用于治疗肝炎，但其溶解性差，生物利用度低。本研究采用纳米沉淀法制备了油酸纳米混悬剂，并对其进行了系统的表征。所得纳米悬浮液的平均粒径为284.9 nm，多分散指数为0.216。透射电子显微镜和原子力显微镜显示药物在纳米悬浮液中以球形或近球形纳米颗粒存在。差示扫描量热法和X-射线衍射研究表明，油酸是以无定形状态存在于冻干的纳米混悬液。在25 ℃下，纳米化后油酸的饱和溶解度增加了约6倍（25.72 μ g mL（-1）对4.37 μ g mL（-1））。在体外药物释放实验中，冻干纳米混悬液显示出比粗药物粉末更快的药物溶出速率（约100%）。前20 min内释放率分别为90%和15%，120 min内释放率接近95%。血清丙氨酸氨基转移酶活性和肝脏丙二醛含量降低证明，油酸纳米混悬液预处理显著增强了油酸对四氯化碳诱导的肝损伤的保护作用。
Oleanolic acid is a naturally derived triterpene used clinically in the treatment of hepatitis in China, but its poor solubility often leads to poor bioavailability. In the present study, oleanolic acid nanosuspensions were prepared by the nanoprecipitation method and then systematically characterized. The average particle size of the obtained nanosuspensions was 284.9 nm, with a polydispersity index of 0.216. Transmission electron microscopy and atomic force microscopy showed that the drug existed as spherical or near-spherical nanoparticles in the nanosuspensions. Differential scanning calorimetry and X-ray diffraction studies indicated that oleanolic acid was present in an amorphous state in the lyophilized nanosuspensions. At 25degreesC, the saturation solubility of oleanolic acid was increased by about 6 times after nanoation (25.72 mug mL(-1) vs 4.37 mug mL(-1)). In the in-vitro drug release experiments, the lyophilized nanosuspensions showed a faster drug dissolution rate than that of the coarse drug powder (approx. 90% vs 15% during the first 20 min), and nearly 95% of the oleanolic acid was released by 120 min. As evidenced by the lower serum alanine aminotransferase activity and liver malondiadehyde content, pre-treatment with oleanolic acid nanosuspensions significantly enhanced the hepatoprotective effect of oleanolic acid against carbon tetrachloride-induced liver injury.