Chem. Pharm. Bull. 53(1) 27—31 (2005)

researched for use in drug toxicity reduction and/or drug targeting to desired target tissues. However, liposomes are rapidly removed from the circulation following their intravenous administration primarily by Kupffer cells in the liver and fixed macrophages in the spleen. Thus, it is important to develop modified liposomes that are able to avoid uptake by the reticuloendothelial system (RES) and extend their circulation half-life in vivo. Many studies have reported that the conjugation of amphipathic polyethylene glycol (PEG) with liposomes (PEG-liposomes) significantly increases the blood circulation liposome half-life compared with those without PEG. In our previous studies, we reported on the effect of PEG-lipid PEG chain length on the membrane characteristics of liposomes. The addition of PEG-lipid to liposomes caused lateral phase separation in the gel and liquid-crystalline states, and the fluidity in the interfacial region of liposomal bilayer membranes was markedly increased by the addition of PEG-lipids. In addition, the permeability of liposomal bilayer membranes decreased compared with those without PEG. From these results, we concluded that the solute permeability of PEG-liposomes is affected by not only the properties of the liposomal bilayer membranes such as phase separation and membrane fluidity, but also the PEG chain length of the liposomal surface. In this study, we investigated the effects of PEG-lipid concentration on CF leakage from PEG-liposomes to elucidate the permeation mechanism of PEG-liposomes in more detail.