Preparation and in Vivo Pharmacokinetics of Chrysophanol Mixed Micelles

OBJECTIVE To prepare chrysophanol-Pluronic F127/glycyrrhizic acid(Chry-F127/GA) mixed micelles, characterize them, and evaluate their in vivo pharmacokinetics in rats.

METHODS Chry-F127/GA was prepared using the solvent evaporation method. The formulation was optimized using single-factor tests combined with response surface methodology. The optimized Chry-F127/GA was characterized. Chrysophanol bulk drug and Chry-F127/GA micelle solution were administered via tail vein injection. Blood samples were collected at different time points, and the plasma concentration of chrysophanol was determined by HPLC. The obtained plasma concentration data were fitted using the PK Solver 2.0 program to derive pharmacokinetic parameters.

RESULTS The optimal formulation for preparing Chry-F127/GA was as follows: chrysophanol amount of 3 mg, drug loading ratio of 1∶23, glycyrrhizic acid percentage content of 60%, and carrier concentration of 4 mg·mL⁻¹. The encapsulation rate, drug loading, particle size, and Zeta potential were (84.99±1.63)%, (3.54±0.07)%, (118.425±1.76)nm, and (−22.03±1.47)mV, respectively. No significant changes in micelle particle size, polydispersity index(PDI) and encapsulation rate were observed over 14 d of storage. Transmission electron microscopy(TEM) revealed that the prepared nanomicelles had a uniform, spherical appearance. Differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR) results showed that chrysophanol existed in an amorphous form within the mixed micelles. Cellular uptake assay results demonstrated the micellar formulation enhanced the uptake of chrysophanol by HepG-2 cells. Pharmacokinetic results showed that compared to the chrysophanol bulk drug group, the Chry-F127/GA micelle group exhibited increased AUC_0-t, decreased total body clearance(CL), and prolonged mean residence time(MRT).

CONCLUSION The prepared Chry-F127/GA micelles have a high encapsulation rate. With a long residence time and prolonged action time in vivo, Chry-F127/GA can improve the bioavailability of chrysophanol.