Correlation of Fixed Aqueous Layer Thickness Around PEG-modified Liposomes with In Vivo Efficacy of Antitumor Agent-containing Liposomes

Ikumi      Sugiyama; Yasuyuki      Sadzuka

doi:10.2174/157016311798109344

Abstract

Liposomes are recognized as useful drug carriers, but have some problems to overcome. Liposomes are easily opsonized with serum proteins (opsonization) and taken up by the reticuloendothelial system (RES) cells, such as spleen and liver. Polyethyleneglycol (PEG) modification on the liposomal membrane forms a fixed aqueous layer and thus prevents opsonization and uptake by the RES. Our research indicates clearly that the electrical potential distributions near the membrane surfaces were different between doxorubicin (DOX)-containing liposomes with and without a PEG coating. Moreover, the value of the fixed aqueous layer thickness (FALT) around the liposome, formed by PEG modification, correlates with the circulation time and antitumor effect in a murine model. In this review, we introduce the observation that measurement of FALT as a physical characteristics is a useful method for demonstrating the antitumor effect of antitumor agent-containing PEG-modified liposomes. The use of this technique may preclude the performance of certain in vivo experiments. Our approach using FALT enables the rapid and reliable development of PEG-modified liposome formulations.

Keywords: Liposome, polyethyleneglycol, FALT, physical character, biological factor, DOX, reticuloendothelial system, antitumor activity, distearoylglycerid, low molecular weight