Synthesis and application of methoxy poly(ethylene glycol)-bile salts conjugates in physicochemical characterization and the pharmacokinetics of the liposomal bifendate in rats

摘要

Stealth liposomes have been broadly investigated as drug delivery or diagnostic agent. However, the materials that possess the ability of stealth, such as DSPE-PEG and Chol-PEG, are either costly or synthetic complex. In this research with different molecular weights (2000-6000 g/mol) of methoxy poly(ethylene glycol)(MePEG), a series of MePEG-bile (MePB) conjugates were generated by an economical and simple method and confirmed by FTIR and ~1H-NMR spectrum. The properties in aqueous solution were studied, including viscosity and surface activity, over a wide concentration range. To elucidate the application of MePB in liposomes (MePBL), conventional liposomes (CL) were prepared, and the influence of the grafting density and the chain length of MePB in liposomes were investigated. The ability of long circulation of MePBL was evaluated by intravenous injection administration in rats. Results indicated that all the liposomes prepared, with or without MePB composition, were similar in micrograph, and the contents of MePB in MePBL were more important than the chain length of MePB for a long circulation in vivo.