LONG-CIRCULATING, POLYETHYLENE GLYCOL-GRAFTED IMMUNOLIPOSOMES

In the last few years a number of advances took place in development o f methodologies for preparation of polyethylene glycol (PEG)-grafted i mmunoliposomes. Several new end-group functionalized PEG lipids were i ntroduced for this purpose. These include pyridyldithiopropionate-PEG- and hydrazide-PEG-PE derivatives, which incorporate well into liposom es and are used for covalent attachment of antibodies to extremities o f the liposome-grafted polymeric chains. Methods previously known for linking antibodies to classical liposomes are in some cases applicable to preparation of PEG-grafted immunoliposomes. In these methods antib odies are fixed directly to the lipid bilayer through reactive residue s on the polar headgroups of lipids. Attributes of the new methods and their comparison to the traditional methods for preparation of immuno liposomes are the main focus of this manuscript. Particular attention is paid to reactivities, potential and observed complications as well as to the relationship between the conjugation chemistry and biologica l activity. It is clear that having numerous possible pathways for gen erating long-circulating immunoliposomes is of great value, since some antibodies tend to be sensitive to different chemical conditions. The current state of the field should facilitate rapid accumulation of in vivo results, which are critical for determination of the true value of this technology.