Change in the character of liposomes as a drug carrier by modifying various polyethyleneglycol-lipids

Abstract

When liposomes, as a superior drug carrier, are injected intravenously, active liposomes as medicines require polyethyleneglycol (PEG) as a modification tool around the liposomal membrane. PEG modification of a liposome forms a fixed aqueous layer, and the trapping by cells of the reticuloendothelial system (RES) is avoided. Hence, PEG-modified liposomes have long circulation in the bloodstream, and passive targeting to tumors has been achieved by PEG modification. We have been studying the passive targeting by liposomes with the expectation of more usefulness. It was proved a correlation between the PEG molecular weight of PEG-modified liposomes and blood circulation time and antitumor effect, too. Liposomes modified by PEG2000 were useful for uptake into tumor cells. We thought that the re-uptake in the liposomal membrane also increased accumulation. Moreover, it was proved that mixing two different PEGs to modify the liposome surface gives a bigger fixed aqueous layer thickness (FALT) around the liposome, giving the liposome strong antitumor activity. Then, we designed a novel PEG-lipid, 1,2-distearoyl-sn-glycero-3-phospho- ethanolamine-PEG (different double arms PEG; DDA-PEG), which had two different PEGs (2000 and 500) in one molecule. One of the innovative characteristics of DDA-PEG-modified liposome (DDAL) is that it heightens the contact ability with tumor cells. DDAL may be an effective DDS carrier for solving various PEG dilemmas. It was observed that passive targeting by PEG-modified liposomes had different characteristics by changing PEG length, anchor type or those combination. Thus, it should be applied to liposomes suitable for various diseases. © 2013 The Pharmaceutical Society of Japan.