AVS 47th International Symposium
    Biomaterial Interfaces Wednesday Sessions
       Session BI-WeA

Paper BI-WeA10
Investigation of Protein Interactions with Poly (Ethylene Glycol) Modified Liposomes

Wednesday, October 4, 2000, 5:00 pm, Room 202

Session: Non-fouling Surfaces
Presenter: J.L. Brash, McMaster University, Canada
Authors: J.L. Brash, McMaster University, Canada
M.E. Price, McMaster University, Canada
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Liposomes have considerable potential as drug delivery vehicles. However unmodified liposomes are rapidly removed from the circulation by the reticuloendothelial system. This is believed to be initiated by adsorption of plasma proteins. Modification of liposomes with poly(ethylene glycol) (PEG) has been shown to increase their lifetime in vivo. Although there is some information on protein interactions with conventional liposomes, there is little if any on PEG-modified liposomes. In this study liposome interactions with fibrinogen in buffer and with plasma have been investigated. Sucrose-loaded large unilamellar liposomes were prepared. Dry phospholipid films (unmodified or modified with phosphatidylethanolamine-conjugated PEG (PE-PEG)) were hydrated with sucrose buffer followed by extrusion through two stacked 100 nm polycarbonate membranes. Liposome size distribution was estimated by dynamic light scattering (DLS) with diameters in the range of 135 ± 8 nm. Liposomes were incubated for 3 h in Tris-buffered 125I-fibrinogen solutions. The mixtures were centrifuged and the radioactivity of liposome pellet determined. Liposomes were also incubated in plasma and bound proteins identified by SDS solubilization followed by gel electrophoresis and immunoblotting using antibodies to some 20 plasma proteins. Fibrinogen adsorption was found to increase as solution concentration increased, with no apparent plateau. Adsorbed amounts decreased with incorporation of PEG and with increasing MW of PEG in the range 500-5000. The gels and immunoblots showed that the unmodified and PEG-modified liposomes adsorbed most of the proteins probed for. The protein patterns (relative amounts of each, degradation, activation) were similar.