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

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