Paeoniflorin loaded liposomes modified with glycyrrhetinic acid for liver-targeting: preparation, characterization, and pharmacokinetic study

Abstract

Objective

To enhance the retention times and therapeutic efficacy of paeoniflorin (PF), a liver-targeted drug delivery system has been developed using glycyrrhetinic acid (GA) as a ligand.

Significance

The development and optimization of GA-modified PF liposomes (GPLs) have shown promising potential for targeted delivery to the liver, opening up new possibilities for liver disease treatment.

Methods

This study aimed to identify the best prescriptions using single-factor experiments and response surface methodology. The formulation morphology was determined using transmission electron microscopy. Tissue distribution was observed through in vivo imaging, and pharmacokinetic studies were conducted.

Results

The results indicated that GPLs, prepared using the thin film dispersion method and response surface optimization, exhibited well-dispersed and uniformly sized particles. The in vitro release rate of GPLs was slower compared to PF monomers, suggesting a sustained release effect. The liver-targeting ability of GA resulted in stronger fluorescence signals in the liver for targeted liposomes compared to non-targeted liposomes. Furthermore, pharmacokinetic studies demonstrated that GPLs significantly prolonged the residence time of PF in the bloodstream, thereby contributing to prolonged efficacy.

Conclusion

These findings suggest that GPLs are more effective than PF monomers in terms of controlling drug release and delivering drugs to specific targets, highlighting the potential of PF as a liver-protective drug.

Graphical Abstract

Keywords:

• Paeoniflorin
• liver targeting liposomes
• response surface methodology
• in vitro release
• in vivo pharmacokinetics

Acknowledgments

The authors express their gratitude for the laboratory facilities support provided by Anhui University of Chinese Medicine.

Author contributions

Menghuan Yang contributed to the formulation development, analyses, investigation, and writing. Gang Jiang performed the experiments. Yumeng Li performed the experiments. Weidong Chen provided supervision and project administration. Shantang Zhang provided supervision and project administration. Rulin Wang contributed to supervision, editing, review, and project administration.

Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

Additional information

Funding

This study was financially supported by the National Natural Science Foundation of China (grant number 82104517).