title: The effects of polyethyleneglycol (PEG)-derived lipid on the activity of target-sensitive immunoliposome.
abstract: In this study, serum stability and target-sensitivity of phosphatidylethanolamine (PE) immunoliposomes prepared with dioleoylphosphatidylethanolamine (DOPE), HYB-241 monoclonal antibody that targets p-glycoproteins, and various levels of polyethyleneglycol 2000 dioleoylphosphatidylethanolamine (PEG(2000)-DOPE) were determined. Incubation of calcein-laden pegylated immunoliposomes 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 in 10% serum cell culture medium, all resulted in time-dependent release of calcein from the liposomes. The release of calcein was greatest for immunoliposomes prepared with 0.3 mol% PEG(2000)-DOPE (66% in 1 h). Contrarily, the release of calcein from the other two immunoliposomes reached only approximately 10-3% after same period of incubation. When serum-induced leakage of calcein was investigated for the above liposome preparations, liposomes prepared 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. Together, it would appear that release of calcein from the immunoliposomes prepared with 0.3 mol% PEG(2000)-DOPE is a result of both serum-induced and target-induced destabilization of liposomes. The net release of calcein due to target-induced destabilization of liposomes is calculated to be at approximately 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.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Campus Box C-238, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA. lawrence.ng@uchsc.edu
authors.forename: K
authors.initials: K
authors.lastname: Ng
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Mahapatro
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001812:Blood-Brain Barrier; D002417:Cattle; D002478:Cells, Cultured; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005079:Excipients / Q000737:chemistry*; D007536:Isomerism; D008081:Liposomes; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000097:blood / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013050:Spectrometry, Fluorescence
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D005079:Excipients; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; C017251:1,2-oleoylphosphatidylcholine