Preparation, characterization, pharmacokinetics and effect on blood viscosity of liposomes containing total salvianolic acids

摘要

Fast elimination rate and low AUC have hampered the use of total salvianolic acids (TSA) as a therapeutic agents for cardiovascular and cerebrovascular diseases. In this study, TSA-loaded conventional liposomes and PEGylated liposomes were developed to prolong the systemic circulating time and improve therapeutic effect of TSA. The preparation, macrophage cell uptake, in vitro release, pharmacokinetics and preliminary pharmacodynamics in beagle dogs of liposomal formulation were investigated. The in vitro cell uptake experiment showed that PEGylated liposomes containing 5mol% PEG-DSPE had the best effect on avoiding macrophage phagocytose. By dynamic light scattering sizer and transmission electron microscopy, it was showed that the TSA-loaded liposomes had the mean size about 110-140nm with narrow size distribution. TSA was continuously released from liposomes for more than 24h at 37℃. AUC and t1/2α, t1/2β and of salvianolic acid B (salB) in liposomes were much higher than that in TSA solution. The result of blood viscosity determination indicated that the order in the effect of reducing blood viscosity from highest to lowest was PEGylated liposome>conventional liposome>solution. The present results suggest that conventional liposomes and PEGylated liposomes are promising delivery system for the parenteral administration of TSA.