title: Use of thermodynamic coupling between antibody-antigen binding and phospholipid acyl chain phase transition energetics to predict immunoliposome targeting affinity.
abstract: Thermodynamic analysis of ligand-target binding has been a useful tool for dissecting the nature of the binding mechanism and, therefore, potentially can provide valuable information regarding the utility of targeted formulations. Based on a consistent coupling of antibody-antigen binding and gel-liquid crystal transition energetics observed for antibody-phosphatidylethanolamine (Ab-PE) conjugates, we hypothesized that the thermodynamic parameters and the affinity for antigen of the Ab-PE conjugates could be effectively predicted once the corresponding information for the unconjugated antibody is determined. This hypothesis has now been tested in nine different antibody-targeted echogenic liposome (ELIP) preparations, where antibody is conjugated to dipalmitoylphosphatidylethanolamine (DPPE) head groups through a thioether linkage. Predictions were satisfactory (affinity not significantly different from the population of values found) in five cases (55.6%), but the affinity of the unconjugated antibody was not significantly different from the population of values found in six cases (66.7%), indicating that the affinities of the conjugated antibody tended not to deviate appreciably from those of the free antibody. While knowledge of the affinities of free antibodies may be sufficient to judge their suitability as targeting agents, thermodynamic analysis may still provide valuable information regarding their usefulness for specific applications.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Texas Health Science Center - Houston , Houston, TX , USA.
authors.forename: Melvin E
authors.initials: ME
authors.lastname: Klegerman
authors.forename: Yuejiao
authors.initials: Y
authors.lastname: Zou
authors.forename: Eva
authors.initials: E
authors.lastname: Golunski
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Shao-Ling
authors.initials: SL
authors.lastname: Huang
authors.forename: David D
authors.initials: DD
authors.lastname: McPherson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology*; D004337:Drug Carriers; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D044367:Phase Transition; D010714:Phosphatidylethanolamines / Q000276:immunology*; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008081:Liposomes; D010714:Phosphatidylethanolamines; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine
keywords: Drug delivery; ligand binding; liposomes; targeted formulations; thermodynamic analysis