Liposomes and Immunoliposomes as Carriers for Cytostatic Drugs, Magnetic Resonance Contrast Agents, and Fluorescent Chelates

Abstract

Biological and medical applications of liposomes as carriers for cytostatic drugs, magnetic-resonance contrast agents, and fluorescent markers are presented. The cytostatic effects of liposomal preparations of lipophilic derivatives of cytosine arabinoside (ara-C), namely N⁴-oleyl-ara-C (NOAC) and N⁴-alkyl-ara-C are demonstrated in the mouse Ll210 tumor model. Liposomal drugs were more effective by factors of 2–10 as compared to ara-C administered in aqueous preparations. Synergistic effects of the combination of ara-C and mitoxantrone could be shown, again with significantly increased effects, when the drugs were administered in liposomes. A practical detergent-dialysis method for the preparation of large volumes of sterile liposomes for clinical use is presented. Clinical phase I/II studies of Iiposoma I NOAC and mitoxantrone are currently in progress. Methods of preparation of immunoliposomes, i.e. the coupling of antibodies or antibody subunits to liposome membranes, are discussed' and results of specific immunoliposome – cell binding are presented. Possibilities of increasing the blood circulation times of liposomes by incorporation of lipophilic derivatives of poly(ethylene glycol) into the liposome membranes are shown. The successful application of liposomes as carriers of paramagnetic metal complexes as contrast agents in magnetic-resonance imaging for liver and spleen is documented. Finally, the concept of liposomes as carriers for fluorescent Europium chelates as markers for time-resolved flow cytometric applications are presented.