SPECIFIC TARGETING WITH POLY(ETHYLENE GLYCOL)-MODIFIED LIPOSOMES - COUPLING OF HOMING DEVICES TO THE ENDS OF THE POLYMERIC CHAINS COMBINES EFFECTIVE TARGET BINDING WITH LONG CIRCULATION TIMES

One possibility for bringing drugs to their specific targets is to use the drug-laden liposomes that have been made target- specific by the attachment of appropriate proteins. Such 'directed' proteoliposomes an d most other particles are rapidly removed from the bloodstream, howev er, by the mononuclear phagocytes in the liver and spleen. This causes suboptimal drug accumulation at the target site. Coating the liposome surface with poly(ethylene glycol) (PEG) may prolong the circulation time of liposomes. Using plasminogen as a homing device we have shown that the PEG-modified liposomes with such a homing device coupled to t he ends of the long PEG chains may combine long vesicle circulation ti mes in the blood with high target binding capability. The PEG-coated p roteoliposomes with homing devices attached at the very bilayer surfac e, on the contrary, are longlived but have only little or no capabilit y to bind to their targets.