The effects of polyethyleneglycol (PEG)-derived lipid on the activity of target-sensitive immunoliposome

In this study, serum stability and target-sensitivity of phosphatidylethano lamine (PE) immunoliposomes prepared with dioleoylphosphatidylethanolamine (DOPE), HYB-241 monoclonal antibody that targets p-glycoproteins, and Vario us levels of polyethyleneglycol 2000 dioleoylphosphatidylethanolamine (PEG( 2000)-DOPE) were determined. Incubation of calcein-laden pegylated immunoli posomes prepared with different levels of PEG(2000)-DOPE (0.3, 0.5 and 1.0 mol%) with p-glycoprotein rich bovine brain microvessel endothelial cells i n 10% serum cell culture medium, all resulted in time-dependent release of calcein from the liposomes. The release of calcein was greatest for immunol iposomes prepared with 0.3 mol% PEG(2000)-DOPE (66% in 1 h). Contrarily, th e release of calcein from the other two immunoliposomes reached only simila r to 10-3% after same period of incubation. When serum-induced leakage of c alcein was investigated for the above liposome preparations, liposomes prep ared with 0.3 and 0.5 mol% PEG(2000)-DOPE had the highest leakage level (10 % in 1 h). Contrarily, the release of calcein from liposomes prepared with 1.0 mol% PEG(2000)-DOPE reached only 3% after same period of incubation. To gether, it would appear that release of calcein from the immunoliposomes pr epared with 0.3 mol% PEG(2000)-DOPE is a result of both serum-induced and t arget-induced destabilization of liposomes. The net release of calcein due to target-induced destabilization of liposomes is calculated to be at simil ar to 56%. In contrast, there is no target-induced leakage of calcein from immunoliposomes prepared with either 0.5 or 1.0 mol% PEG(2000)-DOPE. (C) 20 00 Published by Elsevier Science B.V. All rights reserved.