Mixed micelles for enhanced oral bioavailability and hypolipidemic effect of liquiritin: preparation, in vitro and in vivo evaluation

Abstract

Objectives

Liquiritin, as one of the main flavonoids in Glycyrrhiza, exhibits extensive pharmacological effects, such as the anti-oxidant, anti-inflammatory, anti-tumor and so on. Herein, the aqueous solubility and oral bioavailability of liquiritin was purposely enhanced via the preparation of the mixed micelles.

Methods

The liquiritin-loaded micelles (LLM) were fabricated via thin-film dispersion method. The optimal LLM formulation was evaluated through physical properties including particle size (PS), encapsulation efficiency (EE) and drug loading (DL). In vitro accumulate release as well as in vivo pharmacokinetics were also evaluated. Moreover, the hypolipidemic activity of LLM was observed in the hyperlipidemia mice model.

Results

The LLM exhibited a homogenous spherical shape with small mean PS, good stability and high encapsulation efficiency. The accumulate release rates in vitro of the LLM were obviously higher than free liquiritin. The oral bioavailability of the formulation was heightened by 3.98 times in comparison with the free liquiritin. More importantly, LLM increased the hypolipidemic and effect of alleviating lipid metabolism disorder in hepatocytes of liquiritin in hyperlipidemia mice model.

Conclusions

Collectively, the improved solubility of liquiritin in water coupled with its enhanced oral bioavailability and concomitant hypolipidemic activity could be attributed to the incorporation of the drug into the mixed micelles.

Keywords:

• Liquiritin
• micelle
• oral bioavailability
• in vitro release
• hypolipidemic

Disclosure statement

The authors declare that they have no conflicts of interest or personal relationships that could have appeared to influence the work reported in this work.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant 81773695, 81473172, 81503025 and 81720108030] and the National Key Research and Development Program of China [2018YFE0208600].