Preparation and In Vivo Pharmacokinetics of Chrysophanol Mix Micelles

OBJECTIVE To prepare 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 prescription was optimized by single-factor tests combined with response surface methodology. The optimized micelles were characterized. chrysophanol solution and Chry-F127/GA micellar solution were administered to rats via tail vein injection. Blood samples were collected at different time points, and the plasma concentration of chrysophanol was determined by HPLC. The pharmacokinetic parameters were obtained by fitting the concentration-time data using PK Solver 2.0 software.

RESULTS The optimal prescription was as follows: chrysophanol 3 mg, drug loading ratio 1∶23, 60% of GA, and 4 mg·mL⁻¹ carrier concentration. The encapsulation rate, drug loading, particle size, and Zeta potential were(84.99±1.63)%, (3.54±0.068)%, (118.425±1.76)nm, and(−22.03±1.47) mV, respectively. The particle size, polydispersity index (PDI) and encapsulation rate of the micelles did not change significantly within 14 d of placement. Transmission electron microscopy(TEM) images revealed that the micelles were homogeneous and spherical. Differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR) measurements showed that chrysophanol was present in the mixed micelles in an amorphous form. Cellular uptake assay showed that the micellar dosage form enhanced the uptake of chrysophanol by Hepg-2 cells. Pharmacokinetic results showed elevated AUC_0-t, decreased CL, and prolonged MRT in the Chry-F127/GA micelles group compared to the chrysophanol solution group.

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