Pharmacokinetics and Tissue Distribution of Voriconazole Albumin Nanoparticles in Rats / 中国药师

ABSTRACT

Objective: To prepare voriconazole albumin nanoparticles and evaluate the characteristics of pharmacokinetics and tissue distribution in rats.Methods: Voriconazole albumin nanoparticles were prepared by a new ultra-high pressure microfluidization technology.The physicochemical properties of voriconazole albumin nanoparticles were studied, such as the particle size distribution, zeta potential and particle shape.The release of voriconazole from albumin nanoparticles was investigated in pH7.4 phosphate buffered saline.The concentrations of voriconazole in plasma and the other different tissues were determined after the tail-vein injection of voriconazole albumin nanoparticles in rats.Results: Voriconazole albumin nanoparticles were homogeneous small spheres as seen under a transmission electron microscope.The average particle diameter was (121.9±41.6) nm, the polydispersity index was 0.197, and the zeta potential was (-42.1±0.9) mV.In 0.5% Tween-80 phosphate buffered saline (pH7.4), the in vitro cumulative release of voriconazole albumin nanoparticles reached up to 67.5% in 24 h.AUC0-24 of voriconazole albumin nanoparticles and voriconazole injection was (98.27±1.42) and (105.32±1.45) g/L/h, and MRT0-24 was (4.48±0.38) and (4.86±0.51) h, respectively.Conclusion: Voriconazole albumin nanoparticles can prolong the circulation time, and exhibit promising targeting ability in liver, spleen and brain.