Formulation of pluronic F127/TPGS mixed micelles to improve the oral absorption of glycyrrhizic acid

Abstract

Background: Glycyrrhizic acid (GL), a pentacyclic triterpenoid glycoside, has been used as a hepatoprotective agent for the treatment of acute and chronic hepatitis. However, its poor solubility and permeability across the gastrointestinal mucosa limit its clinical efficacy. This study aimed to develop mixed micelles based on pluronic F127 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral bioavailability of GL.

Methods: GL loaded pluronic F127/TPGS mixed micelles (GL-F127/TPGS-MMs) were prepared by thin film hydration method, and their physicochemical properties including particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), X-ray diffraction (XRD) analysis, differential scanning calorimetry (DSC), and drug release were characterized. Furthermore, the pharmacokinetic and biodistribution studies of GL-F127/TPGS-MMs were evaluated in rats and compared with GL solution.

Results: GL-F127/TPGS-MMs were found to be of spherical shape with particle size of (27.41 ± 4.90) nm, EE% of 95.38% and DL% of 12.99%. The results of XRD and DSC indicated that GL was encapsulated in the micelles. Drug release of GL-F127/TPGS-MMs demonstrated a sustained release behavior as compared to GL solution. The pharmacokinetic and biodistribution studies showed a significantly higher oral absorption and liver accumulation of glycyrrhetinic acid (GA) after oral administration of GL-F127/TPGS-MMs as compared to GL solution.

Conclusion: These results suggested F127/TPGS-MMs might be a potential nanocarrier for oral delivery of GL.

Keywords:

• Glycyrrhizic acid
• pluronic F127
• TPGS
• micelles
• tissue distribution
• oral administration

Disclosure statement

The authors declare no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This study was financially supported by Beijing Municipal Science & Technology Commission (No. Z171100001717026), the National Natural Science Foundation of China (Nos. 81803741 and 81873092), and the Military Logistics Comprehensive Fund (No. BKJ16J011).