Oleanolic acid nanosuspensions: preparation, in-vitro characterization and enhanced hepatoprotective effect.
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 25 degrees C, the saturation solubility of oleanolic acid was increased by about 6 times after nanoation (25.72 microg mL(-1) vs 4.37 microg 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 malondialdehyde content, pre-treatment with oleanolic acid nanosuspensions significantly enhanced the hepatoprotective effect of oleanolic acid against carbon tetrachloride-induced liver injury.
Chen
Yajun
Y
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
Liu
Jie
J
Yang
Xiangliang
X
Zhao
Xiaoling
X
Xu
Huibi
H
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000037:antagonists & inhibitors / Q000097:blood; D000818:Animals; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors; D056486:Chemical and Drug Induced Liver Injury; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends; D002681:China; D004304:Dosage Forms; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007279:Injections, Subcutaneous; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy*; D008315:Malondialdehyde / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009828:Oleanolic Acid / Q000138:chemical synthesis / Q000494:pharmacology*; D010316:Particle Size; D012995:Solubility; D013535:Suspensions / Q000138:chemical synthesis*; D014315:Triterpenes / Q000737:chemistry; D014961:X-Ray Diffraction / Q000379:methods
D004304:Dosage Forms; D013535:Suspensions; D014315:Triterpenes; D008315:Malondialdehyde; D009828:Oleanolic Acid; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase