Clearance properties of liposomes involving conjugated proteins for targeting.
This review examines methods of protein conjugation onto liposomes and the effects of surface bound protein on the liposomes' biological behavior. It is evident that the presence of a conjugated protein significantly alters the attributes of targeted liposomes. Specifically, protein conjugation can result in dramatic increases in liposome size, enhanced immunogenicity, and increased plasma elimination. Techniques are discussed for preventing some of the physical (size) and biological (immunogenic) alterations involving the use of PEG-lipids and drug loaded liposomes. In addition, the advantages of conjugating antibodies via carbohydrate moieties, to minimize changes in antibody binding and tertiary structure as well as effectively decreasing plasma elimination, are also discussed. It is, however, apparent that the accessibility of targeted liposomes to extravascular sites is a key step that will require further study and it is, therefore, anticipated that with the development of novel ligands and novel ligand-liposome interactions, the therapeutic utility of targeting strategies will likely be realized.
Tardi
P
INEX Pharmaceuticals Corporation, 100 Glenlyon Parkway, Glenlyon Business Park, Burnaby, B.C., V5J 5JB, Canada
Bally
MB
Harasym
TO