The development of a model system to study the specific binding activity of long-circulating immunoliposomes.

Update Item Information
Title The development of a model system to study the specific binding activity of long-circulating immunoliposomes.
Publication Type dissertation
School or College College of Pharmacy
Department Pharmaceutics & Pharmaceutical Chemistry
Author Gentry, Christine Anne.
Date 1997-08
Description In this dissertation a new method to prepare long-circulating immunoliposomes is described. Both the Fab$\sp\prime$ fragment (a thiolated antigen binding fragment of an antibody) and a thiolated derivative of poly(ethylene glycol) (PEG) were coupled to the liposome's surface via a sulfhydryl reactive phospholipid within the bilayer. The concurrent binding of PEG was not found to reduce the coupling efficiency of the Fab$\sp\prime$ to the liposome. The Fab$\sp\prime$ fragment of the antifluorescyl monoclonal antibody, 4-4-20, was the targeting moiety used to prepare the IL. The antifluorescyl-fluorescein system allows antigen-antibody binding to be observed spectroscopically. The methods used to prepare the Fab$\sp\prime$ fragment and couple it to the liposome, and the presence of PEG did not reduce the intrinsic binding affinity of the Fab$\sp\prime$ fragment for free fluorescein. When fluorescein was bound to the surface of a cell or a solid support there was evidence of interference by the PEG barrier however the observed affinity was still very high. The in vivo circulation times of these liposomes were investigated in rats. PEGylated IL prepared using the modular coupling chemistry developed by our lab were compared to those of PEGylated liposomes prepared with the PEG derivatized phospholipid, PEG-PE, the current literature standard, and to non-PEGylated liposomes and IL. Liposomes (no Fab$\sp\prime$) prepared with either PEG2000-PE or PEG5000-PE were found to circulate longer than non-PEGylated liposomes or IL. Those containing the higher molecular weight PEG circulated longer. The PEGylated IL prepared using the modular coupling method exhibited circulation times that were significantly greater than non-PEGylated liposomes and intermediate between the liposomes prepared with PEG2000-PE and PEG5000-PE. In conclusion, using the modular coupling method, PEGylated IL were efficiently prepared. These IL maintained high binding activity and exhibited prolonged circulation times. Due to the promising results obtained with this model system it is expected that this preparation method can be used to produce more therapeutically relevant long-circulating IL in the future.
Type Text
Publisher University of Utah
Subject Pharmacy; Immunoliposmes
Subject MESH Drug Carriers; Liposomes
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "The development of a model system to study the specific binding activity of long-circulating immunoliposomes." Spencer S. Eccles Health Sciences Library. Print version of "The development of a model system to study the specific binding activity of long-circulating immunoliposomes." available at J. Willard Marriott Library Special Collection. RS43.5 1997 .G46.
Rights Management © Christine Anne Gentry.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,174
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6jt04zz
Setname ir_etd
ID 192869
Reference URL https://collections.lib.utah.edu/ark:/87278/s6jt04zz
Back to Search Results