Glycyrrhizic acid-based self-assembled micelles for improving oral bioavailability of paeoniflorin

Abstract

Background

Paeoniflorin (Pae), a water-soluble monoterpene glucoside, has high potential clinical value in autoimmune and inflammatory diseases. However, the extremely low oral bioavailability of Pae (approximately 3%–4%) limits its formulation development and clinical application. This study aimed to develop micelles using the glycyrrhizic acid (GL) as the carrier to improve the oral absorption of Pae.

Methods

Pae-loaded GL micelles were prepared by the ultrasonic dispersion method and its formulation was optimized by single-factor tests. Characterizations of Pae-loaded GL micelles including particle size, zeta potential, entrapment efficiency (EE), drug loading (DL), morphology, and drug release in vitro were carried out. The single-pass intestinal perfusion and pharmacokinetic studies of Pae-loaded GL micelles were also evaluated in rats and compared with Pae solution and the mixed solution of Pae and GL.

Results

The optimized Pae-loaded GL micelles had EE of (42.21 ± 0.89)%, particle size of (58.89 ± 4.24) nm with PDI of (0.194 ± 0.010), zeta potential of (−24.40 ± 1.90) mV. Pae-loaded GL micelles showed a nearly spherical shape under TEM. Drug release of micelles demonstrated a delayed drug release compared to Pae solution. The single-pass intestinal perfusion study showed a significantly higher permeability of Pae in duodenum (p < 0.05), jejunum (p < 0.05), ileum (p < 0.01) and colon (p < 0.01) intestine after perfusion of Pae-loaded GL micelles as compared to Pae solution. The in vivo pharmacokinetics demonstrated that the C_max and AUC_0–t values of Pae-loaded GL micelles were approximately 2.18- and 3.64-fold superior than the Pae solution.

Conclusion

These results suggested GL could be a potential carrier for the oral delivery of Pae.

Keywords:

• Paeoniflorin
• glycyrrhizic acid
• micelles
• single-pass intestinal perfusion
• oral bioavailability

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 the National Natural Science Foundation of China [No. 81803741 and 81,873,092].