Preparation, characterization, pharmacokinetics and effect on blood viscosity of liposomes containing total salvianolic acids
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.
Total salvianolic acids Conventional liposomes PEGylated liposomes Pharmacokinetics blood viscosity
Jianxin Wang Lihong Zhang Limei Han Dongyan Gao Zhirong Zhang
Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, Peoples Republi Department of Pharmaceutics, West China School of Pharmacy, Sichuan University, Chengdu, Peoples Re
国际会议
上海
英文
104-113
2007-10-19（万方平台首次上网日期，不代表论文的发表时间）