Improvement of oral bioavailability of glycyrrhizin by sodium deoxycholate/phospholipid-mixed nanomicelles

• Published in: Journal of drug targeting 2012-08, Vol.20 (7), p.615-622
• Main Authors: Jin, Shixiao, Fu, Shanshan, Han, Jin, Jin, Shiying, Lv, Qingyuan, Lu, Yi, Qi, Jianping, Wu, Wei, Yuan, Hailong
• Format: Article
• Language: English
• Subjects: acute liver injury; Administration, Oral; Alanine Transaminase - metabolism; Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacokinetics; Anti-Inflammatory Agents - therapeutic use; Aspartate Aminotransferases - metabolism; Biological and medical sciences; Biological Availability; Biphenyl Compounds - therapeutic use; Carbon Tetrachloride; Deoxycholic Acid - administration & dosage; Deoxycholic Acid - chemistry; Disease Models, Animal; Drug Stability; General pharmacology; Glycyrrhizic Acid - administration & dosage; Glycyrrhizic Acid - pharmacokinetics; Glycyrrhizic Acid - therapeutic use; Glycyrrhizin; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Medical sciences; Micelles; Nanoconjugates - administration & dosage; Nanoconjugates - chemistry; oral bioavailability; Particle Size; Pharmaceutical technology. Pharmaceutical industry; pharmacodynamics; pharmacokinetics; Pharmacology. Drug treatments; Phospholipids - administration & dosage; Phospholipids - chemistry; Rats; Rats, Wistar; sodium deoxycholate/phospholipid-mixed nanomicelles; Surface Properties
• ISSN: 1061-186X; 1029-2330
• DOI: 10.3109/1061186X.2012.702770

Glycyrrhizin (GL), extracted from the Glycyrrhiza glabra L., is active triterpenoid saponin components. However, due to its impermeability across the gastrointestinal mucosa, oral bioavailability of the drug was relatively low. To improve its oral bioavailability, formulation of GL as sodium deoxycholate/phospholipid-mixed nanomicelles (SDC/PL-MMs) has been performed in this study. GL-SDC/PL-MMs were produced by a film dispersion method and then investigated using photon correlation spectroscopy (PCS), zeta potential measurement, as well as its physical stability after storage for 10, 20, 30, 60, 90 and 120 days. To verify the theoretical hypothesis, pharmacokinetics and pharmacodynamic studies based on carbon tetrachloride (CCl4)-induced acute liver injury was investigated. Results showed that a narrow size distributed nanomicelles with a mean particle size of 82.99 ± 7.5 nm and a zeta potential of −32.23 ± 1.05 mV was obtained. In the pharmacokinetics, GL-SDC/PL-MMs show a significant superiority in AUC0-t, Cmax and other pharmacokinetic parameters compared with the control group. In the pharmacodynamic studies, compared with the bifendate control group, GL-SDC/PL-MMs showed an equivalent effect in reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST) and improving the pathological changes of liver tissue. These results revealed that SDC/PL-MMs could enhance GL absorption in gastrointestinal tract and pharmacodynamic effect in the treatment of acute liver injury caused by CCl4, and SDC/PL-MMs might be a good choice for oral delivery of poor bioavailability drug like GL.